|
What Are
Gallstones?
MFMER.
2002. Rochester, MN: Mayo Foundation for Medical
Education and Research.
Attenuation of
alcohol-induced apoptosis of hepatocytes in rat livers by
polyenylphosphatidylcholine (PPC).
Mi LJ, Mak KM, Lieber CS. Alcohol Research and Treatment
Center, Bronx Veterans Affairs Medical Center, New York,
New York 10468, USA.
Alcohol Clin Exp Res. 2000 Feb;24(2):207-12
BACKGROUND: Alcohol consumption increases apoptosis of
hepatocytes. This effect appears to be mediated by the
induction of hepatic cytochrome P-4502E1(CYP2E1) and its
generation of free radicals, which results in an enhanced
lipid peroxidation that initiates apoptosis. Because
polyenylphosphatidylcholine (PPC), a soybean extract rich
in polyunsaturated phosphatidylcholines, decreases the
induction of ethanol-specific CYP2E1 and opposes oxidative
stress, we hypothesized that PPC supplementation may
attenuate hepatocyte apoptosis caused by ethanol
ingestion.
METHODS: Twenty-eight male Sprague Dawley rats were
pair-fed Lieber-DeCarli liquid diets containing 36% of
energy as alcohol or an isocaloric amount of carbohydrate
for 28 days. Half of the rats were given PPC (3 g/liter),
whereas the other half received the same amount of
linoleate (as safflower oil) and of choline as the
bitartrate. An additional dose of alcohol (3 g/kg) was
given intragastrically 90 min before the livers were
removed. We assessed apoptosis in formalin-fixed,
paraffin-embedded liver sections by using the TUNEL
(terminal transferase dUTP nick end labeling) assay.
Apoptotic hepatocytes were identified by positive TUNEL
staining in conjunction with condensation of nucleoplasm or
margination of chromatin. In each rat, 20,000 to 60,000
hepatocytes were counted by light microscopy by using
Image-Pro Plus computer software, and the incidence of
apoptosis was expressed as the percentage of total
hepatocytes.
RESULTS: Alcohol feeding resulted in a 4.5-fold increase
in apoptosis of hepatocytes compared to pair-fed control
rats; PPC supplementation decreased the alcohol-induced
apoptosis to less than half. No difference in the incidence
of apoptosis between the control and PPC-supplemented rats
was found in the absence of alcohol. Apoptosis was
distributed randomly in the liver lobules of the rats fed
the control diet, whereas the alcohol-induced apoptosis was
significantly increased in the perivenular area. PPC
supplementation strikingly reduced this effect.
CONCLUSIONS: PPC attenuates alcohol-induced apoptosis of
hepatocytes; this effect may provide a mechanism for PPC's
protection against liver injury, possibly in association
with its antioxidative action via the down-regulation of
ethanol-mediated CYP2E1 induction.
Alcoholic
hepatitis.
Mihas, A.A., Heuman, D.M.
eMed. J. 2002 Jan 2; 3(1)
(http://www.emedicine.com/med/topic101.htm).
Deaths: preliminary data
for 2000.
Minino, A.M., Smith, B.L.
Natl. Vital Stat. Rep. 2001 Oct 9; 49(12): 1-40.
Effect of malotilate on
ethanol-induced gastric mucosal damage in
capsaicin-pretreated rats.
Mirossay L, Kohut A, Mojzis J. Department of
Pharmacology, Faculty of Medicine, Safarik University,
Kosice, Slovak Republic. mirossay@central.medic.upjs.sk
Physiol Res. 1999;48(5):375-81
We studied the role of afferent sensory neurons in
malotilate-mediated gastric mucosal protection. Intact and
capsaicin sensory-denervated rats were used in the
experiments. Gross gastric mucosal injury was assessed and
evaluated as a main criterion of the gastroprotective
effect of the tested substances. Besides malotilate,
methyl-prostaglandin E2 was applied alone or in combination
with malotilate to compare the effects and the mechanism of
action of both substances. The results revealed that both
malotilate as well as methyl-prostaglandin E2 exerted a
significant protective action on 96% ethanol-induced
gastric mucosal damage. However, there were no significant
differences between intact and capsaicin-denervated rats.
Only the use of 50% ethanol as a milder mucosal irritating
agent resulted in significant differences in both groups of
animals. We propose that malotilate (like
methyl-prostaglandin E2) has a gastroprotective effect on
ethanol-induced gastric mucosal injury. This effect is
partly dependent on the sensory nervous system and the
combination of both above substances has an additive
effect.
Gastroprotective effect
of malotilate in indomethacin- and ethanol-induced gastric
mucosal damage.
Mirossay L, Mojzis J, Sallingova Z, Bodnar J, Benicky M,
Boor A, Kohut A. Department of Pharmacology, Faculty of
Medicine, Safarik University, Kosice, Slovak Republic.
Physiol Res. 1996;45(5):405-11
Malotilate as a synthetic substance shares comparable
hepatoprotective properties with various flavonoids. The
gastroprotective effect of some flavonoids prompted us to
ascertain the similar effectiveness of malotilate. The
possible gastroprotectivity was examined in gastric mucosal
damage in rats induced by indomethacin (20 mg.kg-1) or
ethanol (96%). Oral pretreatment with malotilate (25, 50,
100, 200 and 400 mg.kg-1) reduced the extent of lesions
induced by both indomethacin and ethanol. Histological
analyses also revealed a mitigating effect on the severity
of gastric mucosal lesions. Similar results were obtained
in the group of rats pretreated with 5 mg.kg-1 indomethacin
followed by oral administration of 96% ethanol. This
finding suggests that the effect of malotilate on rat
gastric mucosa is independent of endogenous prostaglandin
production.
Peroxisome
proliferator-activated receptors and hepatic stellate cell
activation.
Miyahara T, Schrum L, Rippe R, Xiong S, Yee HF Jr,
Motomura K, Anania FA, Willson TM, Tsukamoto H. Departments
of Medicine and Pathology, Keck School of Medicine of the
University of Southern California, Los Angeles, California
90033, USA.
J Biol Chem. 2000 Nov 17;275(46):35715-22
The present study examined the roles of peroxisome
proliferator-activated receptors (PPAR) in activation of
hepatic stellate cells (HSC), a pivotal event in liver
fibrogenesis. RNase protection assay detected mRNA for
PPARgamma1 but not that for the adipocyte-specific gamma2
isoform in HSC isolated from sham-operated rats, whereas
the transcripts for neither isoforms were detectable in HSC
from cholestatic liver fibrosis induced by bile duct
ligation (BDL). Semi-quantitative reverse
transcriptase-polymerase chain reaction confirmed a 70%
reduction in PPARgamma mRNA level in HSC from BDL. Nuclear
extracts from BDL cells showed an expected diminution of
binding to PPAR-responsive element, whereas NF-kappaB and
AP-1 binding were increased. Treatment of
cultured-activated HSC with ligands for PPARgamma (10
microm 15-deoxy-Delta(12,14)-PGJ(2) (15dPGJ(2)); 0.1
approximately 10 microm BRL49653) inhibited DNA and
collagen synthesis without affecting the cell viability.
Suppression of HSC collagen by 15dPGJ(2) was abrogated 70%
by the concomitant treatment with a PPARgamma antagonist
(GW9662). HSC DNA and collagen synthesis were inhibited by
WY14643 at the concentrations known to activate both
PPARalpha and gamma (>100 microm) but not at those that
only activate PPARalpha (<10 microm) or by a synthetic
PPARalpha-selective agonist (GW9578). 15dPGJ(2) reduced
alpha1(I) procollagen, smooth muscle alpha-actin, and
monocyte chemotactic protein-1 mRNA levels while inducing
matrix metalloproteinase-3 and CD36. 15dPGJ(2) and BRL49653
inhibited alpha1(I) procollagen promoter activity. Tumor
necrosis factor alpha (10 ng/ml) reduced PPARgamma mRNA,
and this effect was prevented by the treatment with
15dPGJ(2). These results demonstrate that HSC activation is
associated with the reductions in PPARgamma expression and
PPAR-responsive element binding in vivo and is reversed by
the treatment with PPARgamma ligands in vitro. These
findings implicate diminished PPARgamma signaling in
molecular mechanisms underlying activation of HSC in liver
fibrogenesis and the potential therapeutic value of
PPARgamma ligands for liver fibrosis.
Extending effects of
phospholipids, cholesterol, and ethanolamines on survival
of adult rat hepatocytes in serum-free primary
culture.
Miyazaki M, Bai L, Namba M. Department of Pathology,
Okayama University Medical School, Japan.
Res Exp Med (Berl). 1991;191(2):77-83
In a serum-free primary culture, membrane lipids, such
as phosphatidylethanolamine, phosphatidylcholine, or
cholesterol, effectively prolonged the survival of adult
rat hepatocytes. These lipids effectively prevented
hepatocytes from morphologic degeneration observed in
control cultures, such as enlargement of cell surface,
degranulation of cytoplasm, and multinucleation. The
maintenance effect of phospholipid precursors,
ethanolamine, or phosphoethanolamine on the
primary-cultured hepatocytes was similar to that of
phospholipids. These effects appear to be due to
stabilization of the plasma membrane.
Acetyl-L-carnitine
treatment stimulates oxygen consumption and biosynthetic
function in perfused liver of young and old
rats.
Mollica MP, Iossa S, Soboll S, Liverini G. Department of
General and Environmental Physiology, University of Naples
Federico II, Italy.
Cell Mol Life Sci. 2001 Mar;58(3):477-84
The effect of treatment with acetyl-L-carnitine on
hepatic mitochondrial respiration and biosynthetic function
in perfused liver from young (90 days) and old (22-24
months) rats was studied. Rats were given a 1.5% (w/v)
solution of acetyl-L-carnitine in their drinking water for
1 month and oxygen consumption together with the rate of
gluconeogenesis, urea synthesis, and ketogenesis with and
without added substrates were measured in perfused liver.
Mitochondrial oxygen consumption was also assessed in liver
homogenate and isolated mitochondria to determine the
maximal capacity for oxidative phosphorylation.
Acetyl-L-carnitine treatment almost completely restored the
age-dependent decline in oxygen consumption,
gluconeogenesis, urea synthesis, and ketogenesis found in
perfused liver of old rats to the levels found in young
rats. In addition, acetyl-L-carnitine treatment increased
oxygen consumption and biosynthetic function in perfused
liver from young rats. After acetyl-L-carnitine treatment,
we found detectable 3-oxoacyl-CoA-transferase activity
associated with a consumption of ketone bodies in young and
old rats. Finally, oxygen consumption measured in
homogenate and isolated mitochondria did not change with
age and acetyl-L-carnitine treatment. Our results show that
in perfused liver, acetyl-L-carnitine treatment slows the
age-associated decline in mitochondrial respiration and
biosynthetic function. In addition, treatment of young rats
with acetyl-L-carnitine has a stimulating effect on liver
metabolism, probably through an increase in ATP
production.
Polyenylphosphatidylcholine attenuates
alcohol-induced fatty liver and hyperlipemia in
rats.
Navder KP, Baraona E, Lieber CS. Alcohol Research and
Treatment Center, Bronx Veterans Affairs Medical Center,
New York, New York, USA.
J Nutr. 1997 Sep;127(9):1800-6
Chronic administration of a soybean-derived
polyenylphosphatidylcholine (PPC) extract prevents the
development of cirrhosis in alcohol-fed baboons. To assess
whether this phospholipid also affects earlier changes
induced by alcohol consumption (such as fatty liver and
hyperlipemia), 28 male rat littermates were pair-fed liquid
diets containing 36% of energy either as ethanol or as
additional carbohydrate for 21 d, and killed 90 min after
intragastric administration of the corresponding diets.
Half of the rats were given PPC (3 g/l), whereas the other
half received the same amount of linoleate (as safflower
oil) and choline (as bitartrate salt). PPC did not affect
diet or alcohol consumption [15.4 +/- 0.5 G/(kg.d)], but
the ethanol-induced hepatomegaly and the hepatic
accumulation of lipids (principally triglycerides and
cholesterol esters) and proteins were about half those in
rats not given PPC. The ethanol-induced postprandial
hyperlipemia was lower with PPC than without, despite an
enhanced fat absorption and no difference in the level of
plasma free fatty acids. The attenuation of fatty liver and
hyperlipemia was associated with correction of the
ethanol-induced inhibition of mitochondrial oxidation of
palmitoyl-1-carnitine and the depression of cytochrome
oxidase activity, as well as the increases in activity of
serum glutamate dehydrogenase and aminotransferases. Thus,
PPC attenuates early manifestations of alcohol toxicity, at
least in part, by improving mitochondrial injury. These
beneficial effects of PPC at the initial stages of
alcoholic liver injury may prevent or delay the progression
to more advanced forms of alcoholic liver disease.
Oxidation of LDL in
baboons is increased by alcohol and attenuated by
polyenylphosphatidylcholine.
Navder KP, Baraona E, Leo MA, Lieber CS. Alcohol
Research and Treatment Center, Bronx Veterans Affairs
Medical Center and Mount Sinai School of Medicine, New
York, NY 10468, USA.
J Lipid Res. 1999 Jun;40(6):983-7
Alcohol taken in moderation may prevent atherosclerosis,
whereas heavy drinking has the opposite effect, in part by
promoting oxidation of low density lipoproteins (LDL), a
pathogenetic factor in atherogenesis. We assess here: 1 )
whether similar alterations can be reproduced in baboons
fed 50% of energy as ethanol (the average intake of
alcoholics) for 7- 8 years, and 2 ) whether such
alterations are affected by supplementation with
polyenylphosphatidylcholine (PPC), a mixture of
polyunsaturated phosphatidylcholines, shown to prevent
alcoholic fatty liver, fibrosis, and cirrhosis. Ten animals
were given the ethanol-containing diet and ten were
pair-fed isocaloric control diets. In half of the pairs,
the diets were supplemented with 2.8 g of
polyenylphosphatidylcholine/1000 kcal. Alcohol feeding
increased LDL-lipoperoxides and made LDL-proteins more
negatively charged, changes that were attenuated or
prevented by PPC. The oxidizability of LDL was determined
in vitro by the formation of conjugated dienes after
oxidation with copper. Alcohol shortened the lag time
(which measures LDL antioxidant capacity); this effect was
normalized by PPC supplementation. By contrast, PPC
produced no changes in the controls. Thus
polyenylphosphatidylcholine, by markedly attenuating the
ethanol-induced increase in LDL oxidation, opposes one of
the effects whereby alcohol promotes atherosclerosis.
Effect of
polyunsaturated phosphatidylcholine on immune mediated
hepatocyte damage.
Neuberger J, Hegarty JE, Eddleston AL, Williams R.
Gut. 1983 Aug;24(8):751-5
Studies were carried out to investigate the mechanisms
underlying the reduction of hepatocellular necrosis
observed when polyunsaturated phosphatidylcholine was
administered to patients with HBsAg negative chronic active
hepatitis. After oral administration of the agent, the
susceptibility of rabbit hepatocytes to both antibody
dependent cell mediated cytotoxicity and mitogen induced
lymphocyte cytotoxicity was substantially reduced. Short
term in vitro incubation of either the hepatocytes or
lymphocytes with polyunsaturated phosphatidylcholine had no
effect on antibody dependent cell mediated cytotoxicity. As
it has been shown that orally administered polyunsaturated
phosphatidylcholine can be incorporated into the liver cell
membrane, it is possible that polyunsaturated
phosphatidylcholine exerts its effect by blocking the
interaction between immune effector cells and
hepatocytes.
Hepatitis
C.
NIDA.
NIDA Community Drug Alert Bulletin 2002 Feb 21.
Bethesda, MD: National Institute on Drug Abuse/National
Institutes of Health/Department of Health and Human
Services.
Cirrhosis of the
Liver
NIDDK.
2000 Jan. NIH Publ. No. 00-1134. Bethesda, MD: National
Institute of Diabetes and Digestive and Kidney
Diseases/National Institutes of Health.
How is cirrhosis
diagnosed?
Nidus.
Well-Connected Report: Cirrhosis 1999a Mar. New York:
Nidus Information Services (www.well-connected.com).
What are the primary
treatments for cirrhosis?
Nidus.
Well-Connected Report: Cirrhosis 1999b Mar. New York:
Nidus Information Services (www.well-connected.com).
Effect of dietary zinc
deficiency on alkaline phosphatase and nucleic acids in
rats.
Okegbile EO, Odunuga O, Oyewo A. Department of
Biochemistry, Ogun State University, Ago-Iwoye,
Nigeria.
Afr J Med Med Sci. 1998 Sep-Dec;27(3-4):189-92
Weanling male albino rats were randomly alloted to zinc
deficient fed (ZnDF) pair-fed (ZnPF) or ad libitum-fed
(ZnAL) dietary treatments. The rats were fed diets with
either low (5 micrograms/g) or adequate (100 micrograms/g)
zinc for 28 days. Zinc deficiency significantly reduced
growth rate by 60% and was associated with a significantly
low feed intake when compared with ZnPF and ZnAL groups.
DNA and RNA contents of the liver were used as indication
of nitrogen metabolism. DNA content was similar for both
ZnPF and ZnAL groups (1.90 and 2.20 mg/g wet weight,
respectively), but significantly different from ZnDF (1.42
mg/g wet weight). Liver RNA values of ZnAL, ZnPF and ZnDF
groups similarly varied (25.0, 20.2 and 14.8 mg/g wet
weight, respectively). Liver, muscle, spleen, femur and
serum zinc concentrations were lowest in rats fed ZnDF
relative to adequate zinc levels. The levels of the
alkaline phosphatase activity was highest in the serum and
lowest in the brain (spleen value was greater than that of
the liver). Alkaline phosphatase activity was similar in
ZnAL and ZnPF groups, but significantly different from
ZnDF. In conclusion, the constitutively expressed growth
rate, DNA level, RNA level, organ/serum zinc contents and
alkaline phosphatase activities were markedly affected by
zinc deficiency in rats.
Antioxidant properties
of lipoic acid and its therapeutic effects in prevention of
diabetes complications and cataracts.
Packer L. Department of Molecular and Cell Biology,
University of California at Berkeley 94720.
Ann N Y Acad Sci. 1994 Nov 17;738:257-64
No Abstract Available
Neuroprotection by the
metabolic antioxidant alpha-lipoic acid.
Packer L, Tritschler HJ, Wessel K. Department of
Molecular and Cell Biology, University of California,
Berkeley 94720-3200, USA.
Free Radic Biol Med. 1997;22(1-2):359-78
Reactive oxygen species are thought to be involved in a
number of types of acute and chronic pathologic conditions
in the brain and neural tissue. The metabolic antioxidant
alpha-lipoate (thioctic acid, 1, 2-dithiolane-3-pentanoic
acid; 1, 2-dithiolane-3 valeric acid; and 6,
8-dithiooctanoic acid) is a low molecular weight substance
that is absorbed from the diet and crosses the blood-brain
barrier. alpha-Lipoate is taken up and reduced in cells and
tissues to dihydrolipoate, which is also exported to the
extracellular medium; hence, protection is afforded to both
intracellular and extracellular environments. Both
alpha-lipoate and especially dihydrolipoate have been shown
to be potent antioxidants, to regenerate through redox
cycling other antioxidants like vitamin C and vitamin E,
and to raise intracellular glutathione levels. Thus, it
would seem an ideal substance in the treatment of oxidative
brain and neural disorders involving free radical
processes. Examination of current research reveals
protective effects of these compounds in cerebral
ischemia-reperfusion, excitotoxic amino acid brain injury,
mitochondrial dysfunction, diabetes and diabetic
neuropathy, inborn errors of metabolism, and other causes
of acute or chronic damage to brain or neural tissue. Very
few neuropharmacological intervention strategies are
currently available for the treatment of stroke and
numerous other brain disorders involving free radical
injury. We propose that the various metabolic antioxidant
properties of alpha-lipoate relate to its possible
therapeutic roles in a variety of brain and neuronal tissue
pathologies: thiols are central to antioxidant defense in
brain and other tissues. The most important thiol
antioxidant, glutathione, cannot be directly administered,
whereas alpha-lipoic acid can. In vitro, animal, and
preliminary human studies indicate that alpha-lipoate may
be effective in numerous neurodegenerative disorders.
The effect of aging and
acetyl-L-carnitine on the pyruvate transport and oxidation
in rat heart mitochondria.
Paradies G, Petrosillo G, Gadaleta MN, Ruggiero FM.
Department of Biochemistry and Molecular Biology,
University of Bari, Italy. g.paradies@biologia.uniba.it
FEBS Lett. 1999 Jul 9;454(3):207-9
The effect of aging and acute treatment with
acetyl-L-carnitine on the pyruvate transport and oxidation
in rat heart mitochondria was studied. The activity of the
pyruvate carrier as well as the rates of pyruvate-supported
respiration were both depressed (around 40%) in heart
mitochondria from aged rats, the major decrease occurring
during the second year of life. Administration of
acetyl-L-carnitine to aged rats almost completely restored
the rates of these metabolic functions to the level of
young control rats. This effect of acetyl-L-carnitine was
not due to changes in the content of pyruvate carrier
molecules. The heart mitochondrial content of cardiolipin,
a key phospholipid necessary for mitochondrial substrate
transport, was markedly reduced (approximately 40%) in aged
rats. Treatment of aged rats with acetyl-L-carnitine
reversed the age-associated decline in cardiolipin content.
As the changes in cardiolipin content were correlated with
changes in rates of pyruvate transport and oxidation, it is
suggested that acetyl-L-carnitine reverses the age-related
decrement in the mitochondrial pyruvate metabolism by
restoring the normal cardiolipin content.
Carnitine: an essential
nutrient?
Plawecki, K.
Nutrition Notes 2001 Sep. Northbrook, IL: Weeks
Publishing.
Alpha-lipoic acid
supplementation prevents symptoms of vitamin E
deficiency.
Podda M, Tritschler HJ, Ulrich H, Packer L. Department
of Molecular and Cell Biology, University of California at
Berkeley, 94720-3200.
Biochem Biophys Res Commun. 1994 Oct 14;204(1):98
alpha-Lipoic acid, an essential cofactor in
mitochondrial dehydrogenases, has recently been shown to be
a potent antioxidant in vitro, as well as being capable of
regenerating vitamin E in vitro. In this study, using a new
animal model for rapid vitamin E deficiency in adult
animals and a new technique for tissue extraction of
oxidized and reduced alpha-lipoic acid, we examined the
antioxidant action of alpha-lipoic acid in vivo. Vitamin
E-deficient adult hairless mice displayed obvious symptoms
of deficiency within five weeks, but if the diet was
supplemented with alpha-lipoic acid the animals were
completely protected. At five weeks on a vitamin
E-deficient diet animals exhibited similar decreases in
tissue vitamin E levels, whether supplemented or
unsupplemented with alpha-lipoic acid: vitamin E levels in
liver, kidney, heart, and skin decreased 70 to 85%; levels
in brain decreased only 25%. These data show that there was
no effect of alpha-lipoic acid supplementation on vitamin E
tissue concentrations, arguing against a role for
alpha-lipoic acid in regenerating vitamin E in vivo.
Dilinoleoylphosphatidylcholine decreases
hepatic stellate cell activation.
Poniachik J, Baraona E, Zhao J, Lieber CS. Alcohol
Research and Treatment Center, Bronx Veterans Affairs
Medical Center, Bronx, NY 10468, USA.
J Lab Clin Med. 1999 Apr;133(4):342-8
The prevention of cirrhosis in alcohol-fed baboons by
the administration of a soybean extract-43% to 50% of which
was dilinoleoyl-phosphatidylcholine (DLPC) and 24% of which
was 1,palmitoyl 2,linoleoyl-phosphatidylcholine (PLPC)-was
associated with a significant reduction in the number of
stellate cells transformed to myofibroblast-like cells. To
study whether these two major phospholipids affect the
similar transformation that occurs by culturing stellate
cells on uncoated plastic, we assessed their effects on
proliferation (by (methyl-3H)-thymidine incorporation into
DNA), expression of alpha-smooth muscle actin and type I
procollagen (by densitometry of Western blots), and
collagen synthesis (by incorporation of tritiated proline
into collagenase-digestible proteins). These manifestations
of stellate cell activation were decreased by 10 micromol/L
DLPC but not by 10 micromol/L PLPC when compared with
controls incubated either with 17 mmol/L ethanol (used as
solvent for the phospholipids) or without addition. These
agents did not affect cell viability, contamination with
other cells, or the capacity of stellate cells to
synthesize protein. Thus DLPC specifically decreases the in
vitro activation of stellate cells, as judged by the
decreases in proliferative activity, alpha-smooth muscle
actin and procollagen I expressions, and collagen
synthesis, whereas PLPC did not show such effects.
alpha-Procollagen (type I) mRNA was not affected by DLPC,
suggesting a post-translational effect. The reduction in
the activation of hepatic stellate cells by DLPC may be
responsible for, or at least contribute to, the prevention
of fibrosis by the polyenylphosphatidylcholine mixture
administered in vivo.
(+)-Cyanidanol-3
changes functional properties of collagen.
Pontz BF, Krieg T, Muller PK.
Biochem Pharmacol. 1982 Nov 15;31(22):3581-9
About 6-7 (+)-cyanidanol-3 molecules are bound per
collagen alpha-chain. The (+)-cyanidanol-3 treated collagen
contains an increased number of pepsin-resistant
cross-links, is less susceptible to attack by mammalian
collagenase, has a higher shrinkage temp and forms
unstructured aggregates. Cell and organ culture studies
show that these biological systems produce less protein and
collagen in the presence of (+)-cyanidanol-3 and that the
newly synthesized collagen is less soluble.
Transection of the
oesophagus for bleeding oesophageal varices.
Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC,
Williams R.
Br J Surg. 1973 Aug;60(8):646-9
No Abstract Available
S-adenosyl-L-methionine
for alcoholic liver diseases.
Rambaldi A, Gluud C. Copenhagen Trial Unit, Centre for
Clinical Intervention Research, Copenhagen University
Hospital, H:S Rigshopitalet, Blegdamsvej 9, Copenhagen,
Denmark, DK-2100. arambaldi@hotmail.com
Cochrane Database Syst Rev. 2001;(4):CD002235
BACKGROUND: Alcohol is a major cause of liver disease in
the Western world today. S-adenosyl-L-methionine (SAMe)
acts as a methyl donor for all known biological methylation
reactions and participates in the synthesis of glutathione,
the main cellular anti-oxidant. Randomised clinical trials
have addressed the question whether SAMe has any efficacy
in patients with alcoholic liver diseases.
OBJECTIVES: The objectives were to assess the efficacy
of SAMe on mortality, clinical symptoms, complications,
liver biochemistry, and liver histology in patients with
alcoholic liver diseases. Adverse events were also
analysed.
SEARCH STRATEGY: The Cochrane Hepato-Biliary Group
Controlled Trials Register, The Cochrane Library, MEDLINE,
EMBASE, and full text searches were combined.
SELECTION CRITERIA: Randomised clinical trials studying
patients with alcoholic liver diseases were included.
Interventions encompassed peroral or parenteral
administration of SAMe at any dose versus placebo or no
intervention. The trials could be double blind, single
blind, or unblinded. The trials could be unpublished or
published as an article, an abstract, or a letter, and no
language limitations were applied.
DATA COLLECTION AND ANALYSIS: All analyses were
performed according to the intention-to-treat method. The
statistical package (RevMan and MetaView) provided by the
Cochrane Collaboration was used. The methodological quality
of the randomised clinical trials was evaluated by
components of quality and the Jadad-score.
MAIN RESULTS: Eight placebo-controlled randomised
clinical trials including a heterogeneous sample of 330
patients with alcoholic liver disease were identified. Only
one trial including 123 patients with alcoholic cirrhosis
used adequate methodology and reported clearly on mortality
and liver transplantation. It demonstrated no significant
effects of SAMe on mortality (Peto odds ratio (OR) 0.53,
95% confidence interval (CI) 0.22 to 1.29), liver related
mortality (OR 0.63, 95% CI 0.25 to 1.58), mortality or
liver transplantation (OR 0.47; 95% CI 0.20 to 1.09), or
patients without complications (OR 0.63, 95% CI 0.30 to
1.31). SAMe was not significantly associated with adverse
events (OR 3.95, 95% CI 0.77 to 20.24).
REVIEWER'S CONCLUSIONS: This systematic review could not
demonstrate any significant effect of SAMe on mortality,
liver related mortality, mortality or liver
transplantation, and liver complications of patients with
alcoholic liver disease. SAMe should not be used for
alcoholic liver disease outside randomised clinical
trials.
N-acetylcysteine
increases liver blood flow and improves liver function in
septic shock patients: results of a prospective,
randomized, double-blind study.
Rank N, Michel C, Haertel C, Lenhart A, Welte M,
Meier-Hellmann A, Spies C. Department of Anesthesiology and
Operative Intensive Care Medicine, University Hospital
Benjamin Franklin, Freie Universitat Berlin, Germany.
Crit Care Med. 2000 Dec;28(12):3799-807
OBJECTIVE: In septic shock, decreased splanchnic blood
flow is reported, despite adequate systemic hemodynamics.
Aacetylcysteine (NAC) was found to increase
hepatosplanchnic blood flow in experimental settings. In
septic shock patients, NAC improved the clearance of
indocyanine green and the relationship of systemic oxygen
consumption to oxygen demand. We investigated the influence
of NAC on liver blood flow, hepatosplanchnic oxygen
transport-related variables, and liver function during
early septic shock.
DESIGN: Prospective, randomized, double-blind study.
SETTING: Septic shock patients admitted to an
interdisciplinary surgical intensive care unit.
PATIENTS: We examined 60 septic shock patients within 24
hrs after onset of sepsis. They were conventionally
resuscitated with volume and inotropes and were in stable
condition. A gastric tonometer was inserted into the
stomach and a catheter into the hepatic vein. Microsomal
liver function was assessed by using the plasma appearance
of monoethylglycinexylidide (MEGX).
INTERVENTIONS: Subjects randomly received either a bolus
of 150 mg/kg iv NAC over 15 mins and a subsequent
continuous infusion of 12.5 mg/kg/hr NAC over 90 mins (n =
30) or placebo (n = 30).
MEASUREMENTS AND MAIN RESULTS: Measurements were
performed before (baseline) and 60 mins after beginning the
infusion (infusion). After NAC, a significant increase in
absolute liver blood flow index (2.7 vs. 3.3 L/min/m2; p =
.01) and cardiac index (5.0 vs. 5.7 L/min/m2; p = .02) was
observed. Fractional liver blood flow index (cardiac
index-related liver blood flow index) did not change. The
difference between arterial and gastric mucosal carbon
dioxide tension decreased (p = .05) and MEGX increased (p =
.04). Liver blood flow index and MEGX correlated
significantly (r(s) = .57; p < or = .01).
CONCLUSIONS: After NAC treatment, hepatosplanchnic flow
and function improved and may, therefore, suggest enhanced
nutritive blood flow. The increase of liver blood flow
index was not caused by redistribution to the
hepatosplanchnic area, but by an increase of cardiac index.
Because of its correlation with liver blood flow index,
MEGX may be helpful in identifying patients who benefit
from NAC treatment in early septic shock.
Reduction in the MK-801
binding sites of the NMDA sub-type of glutamate receptor in
a mouse model of congenital hyperammonemia: prevention by
acetyl-L-carnitine.
Rao KV, Qureshi IA. Division of Medical Genetics,
Sainte-Justine Hospital, Montreal, Que, Canada.
Neuropharmacology. 1999 Mar;38(3):383-94
Our earlier studies on the pharmacotherapeutic effects
of acetyl-L-carnitine (ALCAR), in sparse-fur (spf) mutant
mice with X linked ornithine transcarbamylase deficiency,
have shown a restoration of cerebral ATP, depleted by
congenital hyperammonemia and hyperglutaminemia. The
reduced cortical glutamate and increased quinolinate may
cause a down-regulation of the N-methyl-D-aspartate (NMDA)
receptors, observed by us in adult spf mice. We have now
studied the kinetics of [3H]-MK-801 binding to NMDA
receptors in spf mice of different ages to see the effect
of chronic hyperammonemia on the glutamate
neurotransmission. We have also studied the Ca2+-dependent
and independent (4-aminopyridine (AP) and
veratridine-mediated) release of glutamate and the uptake
of [3H]-glutamate in synaptosomes isolated from mutant spf
mice and normal CD-1 controls. All these studies were done
with and without ALCAR treatment (4 mmol/kg wt i.p. daily
for 2 weeks), to see if its effect on ATP repletion could
correct the glutamate neurotransmitter abnormalities. Our
results indicate a normal MK-801 binding in 12-day-old spf
mice but a significant reduction immediately after weaning
(21 day), continuing into the adult stage. The
Ca2+-independent release of endogenous glutamate from
synaptosomes was significantly elevated at 35 days, while
the uptake of glutamate into synaptosomes was significantly
reduced in spf mice. ALCAR treatment significantly enhanced
the MK-801 binding, neutralized the increased glutamate
release and restored the glutamate uptake into synaptosomes
of spf mice. These studies point out that: (a) the
developmental abnormalities of the NMDA sub-type of
glutamate receptor in spf mice could be due to the effect
of sustained hyperammonemia, causing a persistent release
of excess glutamate and inhibition of the ATP-dependent
glutamate transport, (b) the modulatory effects of ALCAR on
the NMDA binding sites could be through a repletion of ATP,
required by the transporters to efficiently remove
extracellular glutamate.
Subclinical hepatic
encephalopathy predicts the development of overt hepatic
encephalopathy.
Romero-Gomez M, Boza F, Garcia-Valdecasas MS, Garcia E,
Aguilar-Reina J. Hepatology Unit, Hospital Universitario de
Valme, Sevilla, Spain.
Am J Gastroenterol. 2001 Sep;96(9):2718-23
OBJECTIVES: In patients with compensated liver cirrhosis
the clinical repercussions of detecting subclinical hepatic
encephalopathy (SHE) are unclear. We present a long-term
follow-up study in cirrhotic patients to examine the
relationship between SHE and subsequent episodes of overt
hepatic encephalopathy.
METHODS: A total of 63 cirrhotic patients were studied
by Number Connection Test and auditory evoked potentials.
We determined glutamine, ammonia, zinc, glutamate, urea,
and ratio of branched chain amino acids to aromatic amino
acids, and Child-Pugh classification.
RESULTS: Of 63 patients, 34 (53%) exhibited SHE.
Nineteen out of 63 (30%) developed overt hepatic
encephalopathy during follow-up. Hepatic encephalopathy in
follow-up was related to alcoholic etiology, ammonia,
glutamine, zinc, ratio of branched chain amino acids to
aromatic amino acids, liver function, presence of
esophageal varices, and detection of SHE (84% of patients
who exhibited hepatic encephalopathy in follow-up showed
SHE). In Cox-regression, glutamine levels, SHE, esophageal
varices, and Child-Pugh class were the independent
variables related to hepatic encephalopathy in
follow-up.
CONCLUSIONS: SHE (defined on the basis of number
connection test or auditory evoked potentials alteration)
could predict a subsequent episode of overt hepatic
encephalopathy. Lower glutamine levels, presence of
esophageal varices, and liver dysfunction were also related
to the development of overt hepatic encephalopathy.
The effect of
malotilate on type III and type IV collagen, laminin and
fibronectin metabolism in dimethylnitrosamine-induced liver
fibrosis in the rat.
Ryhanen L, Stenback F, Ala-Kokko L, Savolainen ER.
Department of Internal Medicine, University of Oulu,
Finland.
J Hepatol. 1996 Feb;24(2):238-45
BACKGROUND/AIMS: Dimethylnitrosamine-induced liver
damage was used as an experimental model to study the
effect of malotilate on liver fibrosis.
METHODS: Deposition of type III and IV collagens,
laminin and fibronectin were studied from liver section by
immunohistochemical techniques using specific antibodies.
Serum concentrations of aminoterminal propeptide of type
III procollagen, and aminoterminal and carboxyterminal
domains of type IV collagen were determined by
radioimmunoassays from both malotilate-treated and
untreated animals with dimethylnitrosamine injury.
RESULTS: A significant elevation of all three serum
parameters was observed after 3 weeks of hepatic injury in
animals without malotilate treatment, and a constant
increase was noted in the amounts of hepatic type III and
IV collagens, laminin and fibronectin. Malotilate prevented
increases in serum markers of type III and IV collagen
synthesis as well as accumulation of the collagens, laminin
and fibronectin in the liver.
CONCLUSIONS: The results suggest that serum marker
determinations can be used to monitor changes in type III
and IV collagen synthesis in the liver. The data indicate
that malotilate has a preventive effect in
dimethylnitrosamine-induced experimental hepatic
fibrosis.
Effect of silymarin on
chemical, functional, and morphological alterations of the
liver. A double-blind controlled study.
Salmi HA, Sarna S.
Scand J Gastroenterol. 1982 Jun;17(4):517-21
One hundred and six consecutive patients with liver
disease were selected on the basis of elevated serum
transaminase levels. The patients were randomly allocated
into a group treated with silymarin (treated) and a group
receiving placebo (controls). Ninety-seven patients
complete the 4-week trial-47 treated and 50 controls. In
general, the series represented a relatively slight acute
and subacute liver disease, mostly induced by alcohol
abuse. There was a statistically highly significantly
greater decrease of S-SGPT (S-ALAT) and S-SGOT (S-ASAT) in
the treated group than in controls. Serum total and
conjugated bilirubin decreased more in the treated than in
controls, but the differences were not statistically
significant. BSP retention returned to normal significantly
more often in the treated group. The mean percentage
decrease of BSP was also markedly higher in the treated.
Normalization of histological changes occurred
significantly more often in the treated than in
controls.
The influence of
1,5-dicaffeoylquinic acid on serum lipids in the
experimentally alcoholized rat.
Samochowiec, L., Wojcicki, J., Kadykow, M.
Panminerva Med. 1971; 13(11): 87.
No Abstract Available
An experimental and
clinical study of energy-protein metabolism and host
defense-repair mechanism in postoperative period--a
significance of administration of branched chain amino
acid. [Article in Japanese]
Shimazu Y. First Department of Surgery, Sapporo Medical
College, Japan.
Nippon Geka Gakkai Zasshi. 1990 Oct;91(10):1534-47
The aim of this study is to evaluate in vivo the effect
of branched chain amino acid BCAA). Experimentally, hepatic
energy production and protein synthetic rate were measured
in gastrectomized rat which was infused BCAA
postoperatively. Clinically, following indices were
examined in prospectively randomized patients who underwent
abdominal operation and were administered with conventional
total parenteral nutrition keeping Calorie/N ratio about
150, including nitrogen balance, urinary 3-methylhistidine,
retinol binding protein, B lymphocyte percentage and
lymphocyte blastogenesis by phytohemagglutinin.
Furthermore, plasma BCAA with their keto-analog level,
Factor XIII and opsonic activity were determined in another
group of patients who received full strength load of BCAA
immediately after subtotal or total gastrectomy, in a
controlled prospective randomized double-blinded manner.
Results obtained from above mentioned measurements
exhibited significant improvement by the administration of
BCAA. From these findings, it is suggested that BCAA
sustains energy-protein metabolism, supports
immunocompetence and promotes wound healing under
moderately stressed condition where catabolic response is
physiologically compensated.
Biochemical effects of
the flavonolignane silibinin on RNA, protein and DNA
synthesis in rat livers.
Sonnenbichler J, Zetl I.
Prog Clin Biol Res. 1986;213:319-31
No Abstract Available
Hepatitis
C.
Strickland, D.K.
eMed. J. 2002 Jan 16
(http://www.emedicine.com/ped/topic979.htm).
Malotilate completely
inhibits CCl4-induced liver cirrhosis in rats: biochemical
and morphological analysis.
Suzuki T. Department of Pathology II, Fukushima Medical
College, Japan.
Fukushima J Med Sci. 1992 Jun;38(1):19-33
Malotilate, diisopropyl 1,3-dithiol-2-ylidenemalonate,
is a relatively recently synthesized hepatotrophic chemical
substance. Its inhibitory effect on rat liver cirrhosis
induced by carbon tetrachloride (CCl4) was biochemically
and morphologically investigated for 10 weeks, since this
chemical had been reported to suppress liver damage caused
by CCl4 or in vitro collagenogenesis of human fibroblasts.
Concomitant administration of malotilate with CCl4
completely suppressed liver cell necrosis and markedly
inhibited fatty change of hepatocytes in the first three
weeks of the experiment. During the six to ten weeks of the
experimental period, liver cirrhosis was perfectly
inhibited by malotilate. Previously established liver
cirrhosis, however, could not be normalized by malotilate
treatment. Precise mechanism of the inhibitory effect of
malotilate on liver cirrhosis is not elucidated, but this
substance is clearly effective for preventing liver cell
damage and/or liver cirrhosis caused by CCl4.
Effects of malotilate
treatment on alcoholic liver disease.
Takase S, Matsuda Y, Yasuhara M, Takada A. Department of
Internal Medicine, Kanazawa Medical University, Ishikawa,
Japan.
Alcohol. 1989 May-Jun;6(3):219-22
Malotilate, a new hepatotrophic drug, improves serum
transaminase levels and the markers of protein metabolism
in the liver in chronic liver diseases. However, the
effects of malotilate on alcoholic liver disease are not
well known. In the present study, the effects of this drug
on the recovery process of alcoholic liver disease after
abstinence were analyzed. Many hepatic test values were
significantly improved after abstinence from alcohol in
both the malotilate-treated and nontreated control groups.
However, the Normotest values improved significantly only
in the malotilate group, and not in the control group. The
improvement rates for choline esterase activity were
significantly greater in the malotilate group than in the
control group. Serum albumin levels significantly increased
in the malotilate group but not in the control group.
Changes in the serum markers of hepatic fibrogenesis were
not different between the 2 groups. These results indicate
that malotilate accelerates the recovery of impaired
protein metabolism in alcoholic liver disease and that this
drug may be useful for the treatment of alcoholic liver
diseases.
N-Acetylcysteine
induces shedding of selectins from liver and intestine
during orthotopic liver transplantation.
Taut FJ, Schmidt H, Zapletal CM, Thies JC, Grube C,
Motsch J, Klar E, Martin E. Department of Anaesthesiology,
University of Heidelberg, Heidelberg, Germany.
taut@narkose.net
Clin Exp Immunol. 2001 May;124(2):337-41
In orthotopic liver transplantation (OLT),
N-acetylcysteine (NAC) reduces ischaemia/reperfusion (I/R)
injury, improves liver synthesis function and prevents
primary nonfunction of the graft. To further elucidate the
mechanisms of these beneficial effects of NAC, we
investigated influence of high-dose NAC therapy on the
pattern of adhesion molecule release from liver and
intestine during OLT. Nine patients receiving allograft OLT
were treated with 150 mg NAC/kg during the first hour after
reperfusion; 10 patients received the carrier only. One
hour after reperfusion, samples of arterial, portal venous
and hepatic venous plasma were taken and blood flow in the
hepatic artery and the portal vein was measured. Absolute
concentrations of sICAM-1, sVCAM-1, sP-selectin and
sE-selectin were not markedly different. However, balance
calculations showed release of selectins from NAC-treated
livers as opposed to net uptake in controls (P < or =
0.02 for sP-selectin). This shedding of selectins might be
a contributing factor to the decrease in leucocyte
adherence and improved haemodynamics found experimentally
with NAC-treatment.
Liver,
transplant.
Thomas, G., McNamara, R.M.
eMed. J. 2001 November 19, 2001
(http://www.emedicine.com/aaem/topic458.htm).
Blood viscosity and red
cell morphology in subjects suffering from cirrhosis before
and after treatment with S-adenosyl-L-methionine
(SAMe).
Turchetti V, Bellini MA, Leoncini F, Petri F, Trabalzini
L, Guerrini M, Forconi S. Istituto di Medicina Interna e
Geriatria, Universita degli Studi di Siena, Italy.
images@unisi.it
Clin Hemorheol Microcirc. 2000;22(3):215-21
Alterations of fluidity of the hepatocytic membrane and
of the transport related systems are the basis of the
cholesteatic syndrome and favour the tissue accumulation of
cytotoxic metabolites. S-Adenosyl-L-Methionine (SAM) is a
natural molecule which acts as a giver of methylic groups
and as an enzymatic activator in several enzymatic actions
of transmethylase and of transulphuration and plays a key
role in biochemical processes of hepatic cell. The aim of
our study was to evaluate the effects of SAM on the
restoration of the membrane fluidity and on the hepatic
function in general. In studying the fluidity of the cell
membrane we evaluated some hemorheological parameters
(total blood viscosity and red cell morphology). Fluidity
of the red cell membrane is one of the most important
elements of red cell rheology. We studied 15 patients
(Group A) suffering from micro- and macro-nodular cirrhosis
verified through hepatic biopsy, with alcoholic or
post-viral causes. We evaluated the values of: blood
viscosity (with a cone-plate rheometer by Carri-med),
haematocrit, plasma fibrinogen and the erythrocytic
morphology at the optical microscope with the
Zipursky-Forconi method before and after 7 days of therapy
with SAM i.v.. Data were compared with those of a similar
group (Group B) treated with traditional therapy only
(hyposodic and hypoprotein diet supplemented with
multivitamin preparations, vitamin K in particular, if
necessary, and potassium sparing diuretics). We also
measured biliary salts, alkaline phosphatase, transaminase
and gamma-GT. In the first group we observed a
statistically significant reduction of blood viscosity,
haematocrit didn't change significantly; biliary salts
reduced in a statistically significant way. Evaluation of
red cell morphology showed in all cases a pathological
percentage (>15%) of echinocytes and knizocytes which
reduced to a mean of 5% after SAM therapy. We observed no
further modifications of the other hemorheological
parameters. Results demonstrate that SAM has a positive
action on the fluidity of the membrane, as indicated by the
improvement of haemorheological parameters and by the
significant decrease of biliary salts, indicating the
presence of cholesteasis.
Evidence of hepatic
endogenous hydrogen peroxide in bile of selenium-deficient
rats.
Ueda Y, Matsumoto K, Endo K. Department of Physical
Chemistry, Showa Pharmaceutical University, 3-3165,
Higashi-Tamagawagakuen, Machida, Tokyo, 194-8543,
Japan.
Biochem Biophys Res Commun. 2000 May
19;271(3):699-702
Hepatic endogenous hydrogen peroxide (H(2)O(2)) in bile
of selenium-deficient rats (SeD) was for the first time
found using the electron spin resonance (ESR) spin-trap
technique, and the relationship between glutathione
peroxidase (GPX) activity and H(2)O(2) amount is discussed.
Normal rats and four groups of rats fed a
selenium-deficient diet with different feeding periods were
examined. The results showed that the GPX activity
decreased depending on the feeding period with the
selenium-deficient diet and that the hepatic endogenous
H(2)O(2) amount in the bile of the rats fed the
selenium-deficient diet for the longest period (a week
before birth to 8 weeks old) was drastically higher than
those in other groups of rats (P < 0.005). We found that
generation of H(2)O(2) due to the decrease in the GPX
activity has a threshold value. The results suggest that an
exposure to selenium deficiency for long term will cause
oxidative stress. Copyright 2000 Academic Press.
Selectivity of
silymarin on the increase of the glutathione content in
different tissues of the rat.
Valenzuela A, Aspillaga M, Vial S, Guerra R.
Planta Med. 1989 Oct;55(5):420-2
Silymarin, a flavonoid extracted from the seeds of the
milk thistle, Silybum marianum, increases the redox state
and the total glutathione content of the liver, intestine,
and stomach of the rat. The same treatment does not affect
the levels of the tripeptides in the kidney, lung, and
spleen. This selective effect of the flavonoid on the
digestive organs is ascribed to its pharmacokinetics on the
digestive track, where the biliary concentration of
silymarin is increased and maintained via the
entero-hepatic circulation.
Gallstones:
Cause
WebMD.
2002 Jul 19 (last update, 12/31/01)
(http://webmd.lycos.com/content.healthwise/141/35096.htm).
Lung preconditioning
with N-acetyl-L-cysteine prevents reperfusion injury after
liver no flow-reflow: a dose-response study.
Weinbroum AA, Kluger Y, Ben Abraham R, Shapira I,
Karchevski E, Rudick V. Department of Anesthesiology, Tel
Aviv Sourasky Medical Center, Israel.
draviw@tasmc.health.gov.il
Transplantation. 2001 Jan 27;71(2):300-6
BACKGROUND: Circulating xanthine oxidase activity and
the generated oxidants have been linked to lung reperfusion
injury from no flow-reflow conditions in other organs after
organ transplantation or surgery. N-acetyl-1-cysteine
(NAC), an oxidant scavenger, promotes glutathione in its
reduced form (GSH) that is depleted during ischemia. We
have recently demonstrated its efficacy in protecting lungs
from reperfusion injury if administered during reperfusion
of postischemic liver. We now investigated whether
preconditioning of lungs with NAC could attenuate lung
respiratory or vascular derangement after no flow-reflow
(ischemia-reperfusion, IR) and if this depends on lung GSH
levels.
METHODS: Rat isolated livers were stabilized and
perfused with modified Krebs-Henseleit solution (KH)
(control, n=12) or made ischemic (no flow, IR-0, n=12) for
2 hr. Meanwhile, lungs were isolated, ventilated, and
stabilized (KH+bovine albumin 5%). Serial perfusion (15
min) of liver+lung pairs took place followed by lung only
recirculation (45 min) with the accumulated solution.
Another three controls and three ischemic groups included
lungs treated during stabilization with NAC at 100 mg x
kg(-1), 150 or 225 mg x kg(-1) (in 2.5, 3.7 or 5.5 mmol
solutions, respectively). Results. Ischemic liver damage,
expressed by circulating hepatocellular constituents, was
associated with pulmonary artery and ventilatory pressure
increases by 70-100% of baseline, abnormal wet-to-dry
weight ratio, and abnormal bronchoalveolar lavage volume
and content in the IR-0 (nontreated) and the IR-100 and
IR-225 pretreated lungs. NAC-150 pretreatment afforded
preservation for most parameters. GSH content in the IR-150
lung tissue was only 11% higher than that of IR-225, but
2-fold that in IR-0 and IR-100 GSH lungs.
CONCLUSION: Lung preconditioning with NAC prevents
reperfusion injury but not in a dose-related manner.
Although enhanced GSH tissue content explains lung
protection, GSH-independent NAC activity is another
possibility.
Effects of
1,5-dicaffeoylquinic acid (cynarin) on cholesterol levels
in serum and liver of acute ethanol-treated
rats.
Wojcicki J.
Drug Alcohol Depend. 1978 Mar;3(2):143-5
The effect of 1,5-dicaffeylquinic acid (Cynarine) on
total cholesterol levels in serum and liver of acute
ethanol-treated rats was studied. Male Wister rats were
administered ethyl alcohol, 6 g/kg per day by gavage over
three days. In rats treated with ethanol alone, the serum
and hepatic cholesterol showed a significant rise of 44 and
75%, respectively. In rats receiving ethanol and Cynarine
simultaneously, a distinct reduction of the serum and
hepatic cholesterol levels was observed.
Cirrhosis.
Wolf, D.C.
eMed. J. 2001 Sep 6
(http://www.emedicine.com/med/topic3183.htm).
Cirrhosis and its
disorders.
Workman, J.J.
Liver Disorders Sourcebook 1999, p. 48. Los Angeles:
Lowell House.
Eds. Biomedical and
Clinical Aspects of Coenzyme Q
Yamamura, Y., Folkers, K., Ito, Y.,
Volume 2 1980. Amsterdam: Elsevier.
Plant proteins in
relation to human protein and amino acid
nutrition.
Young VR, Pellett PL. Clinical Research Center,
Massachusetts Institute of Technology, Cambridge 02142.
Am J Clin Nutr. 1994 May;59(5 Suppl):1203S-1212S
Plant protein foods contribute approximately 65% of the
per capita supply of protein on a worldwide basis and
approximately 32% in the North American region. These
sources of protein are discussed in relation to their amino
acid content, human amino acid requirements, and dietary
protein quality. Mixtures of plant proteins can serve as a
complete and well-balanced source of amino acids for
meeting human physiological requirements. This short review
ends with a list of series of myths and realities
concerning the relationship between plant protein and human
nutrition and a list of some nutritional issues of concern
to the health professional and informed consumer.
Protective role of
selenium against hepatitis B virus and primary liver cancer
in Qidong.
Yu SY, Zhu YJ, Li WG. Cancer Institute, Chinese Academy
of Medical Sciences, Peking Union Medical College, Beijing,
China.
Biol Trace Elem Res. 1997 Jan;56(1):117-24
High rates of hepatitis B virus (HBV) infection and
primary liver cancer (PLC) are present in Qidong county.
Epidemiological surveys demonstrated an inverse association
between selenium (Se) level and regional cancer incidence,
as well as HBV infection. Four-year animal studies showed
that dietary supplement of Se reduced the HBV infection by
77.2% and liver precancerous lesion by 75.8% of ducks,
caused by exposure to natural environmental etiologic
factors. An intervention trial was undertaken among the
general population of 130,471. Individuals in five
townships were involved for observation of the preventive
effect of Se. The 8-yr follow-up data showed reduced PLC
incidence by 35.1% in selenized table salt supplemented vs
the nonsupplemented population. On withdrawal of Se from
the treated group, PLC incidence rate began to increase.
However, the inhibitory response to HBV was sustained
during the 3-yr cessation of treatment. The clinical study
among 226 Hepatitis B Surface Antigen (HBsAg)-positive
persons provided either 200 micrograms of Se in the form of
selenized yeast tablet or an identical placebo of yeast
tablet daily for 4 yr showed that 7 of 113 subjects were
diagnosed as having PLC in the placebo group, whereas no
incidence of PLC was found in 113 subjects supplemented
with Se. Again on cessation of treatment, PLC developed at
a rate comparable to that in the control group,
demonstrating that a continuous intake of Se is essential
to sustain the chemopreventive effect.
Effect of
N-acetylcysteine and deferoxamine on endogenous antioxidant
defense system gene expression in a rat hepatocyte model of
cocaine cytotoxicity.
Zaragoza A, Diez-Fernandez C, Alvarez AM, Andres D,
Cascales M. Instituto de Bioquimica (CSIC-UCM), Facultad de
Farmacia, Universidad Complutense, Plaza de Ramon y Cajal
sn, 28040, Madrid, Spain.
Biochim Biophys Acta. 2000 Apr 17;1496(2-3):183-95
In the present study we investigated on cultures of
hepatocytes from phenobarbital-pretreated rats, the effect
of the antioxidants, 0.5 mM N-acetylcysteine (NAC) or 1.5
mM deferoxamine (DFO), previously incubated for 24 h and
coincubated with cocaine (0-1000 microM) for another 24 h.
Cocaine cytotoxicity was monitored by either the lysis of
the cell membranes or apoptosis. Lysis of the cell
membranes was evidenced by lactate dehydrogenase leakage,
apoptosis was observed by detecting a hypodiploid peak
(<2C) in DNA histograms obtained by flow cytometry,
peroxide production was quantified with 2',
7'-dichlorodihydrofluorescein diacetate and gene expression
of the antioxidant enzymes: Mn- and Cu,Zn-superoxide
dismutases, catalase and glutathione peroxidase were
measured by Northern blot analysis. NAC and DFO
significantly decreased the extent of lysis of cell
membranes and apoptosis, and the antiapoptotic effect was
parallel to peroxide generation. By the effect of NAC and
DFO, significant increases were detected in the levels of
mRNA of catalase, manganese superoxide dismutase and
glutathione peroxidase. From these results we conclude that
NAC or DFO, when incubated in the presence of cocaine,
exerted a protective effect against cocaine toxicity at the
level of both lysis of the membranes and apoptosis. This
protective effect, in the case of NAC, was directed towards
an increase in antioxidant enzyme expression, and in the
case of DFO against reactive oxygen species generation.
The effect of folic
acid on the drug metabolizing liver function in man with
viral hepatitis.
Zviarynski IU, Zavodnik LB. Laboratory of Biochemical
Pharmacology, Institute of Biochemistry, Grodno, Belarus.
zverin@biochem.belpak.grodno.by
Exp Toxicol Pathol. 1999 Jul;51(4-5):455-7
The investigations were carried out on 31 patients (16
men and 15 women, at the age of 20-50) with viral
hepatitis. The all patients were divided at two groups. The
first group (12 man) received usual treatment (diet,
corsil), the second group (19 man) received in addition to
the base treatment folic acid (5 mg per day, 10 days). It
was found, that at patients with viral hepatitis was
decreased the activity of monooxygenase system of liver.
So, period of semielimination (T1/2) of antipyrine (AP) was
greater in 1,4 time, area under the pharmacokinetic curve -
1,5 time and clearance was below by 39% than in volunteers
(29 man). On day of treatment only by corsil, the rate of
elimination of AP and clearance were increased by 34 and
31% (p < 0.05) respectively, T1/2 was decreased by 23%
(p < 0.05) and area under the pharmacokinetic curve - 17
%. On 10 day of treatment by corsil with folic acid (5 mg
per day), the rate of elimination of AP and clearance was
increased by 43% (p < 0.05), area under the
pharmacokinetic curve and T 1/2 were decreased by 30 and
33% (p < 0.05) respectively. The positive effect of
folic acid in treatment of hepatitis at restoration period
may be cause participating its derivatives in de novo
nucleotide synthesis.
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