Life Extension Magazine August 2010
Radioprotection of Swiss albino mice by Emblica officinalis.
The fruit pulp of Emblica officinalis (EO) is an important drug used in Indian systems of medicine for several diseases and as a tonic. In view of its multifarious uses, the plant extract (aqueous) was tested for its radioprotective properties against sublethal gamma radiation (9 Gy) in Swiss albino mice. Animals were divided into two groups and irradiated with gamma radiation externally, with or without EO extract, which was given orally at different doses before irradiation. The dose of fruit pulp extract found to be most effective against radiation was 100 mg/kg b.wt. This dose increased the survival time and reduced the mortality rate of mice significantly. Furthermore, body weight loss in EO administered irradiated animals was significantly less in comparison with animals who were given radiation only.
Phytother Res. 2005 May;19(5):444-6
Inhibitory effect of ascorbic acid post-treatment on radiation-induced chromosomal damage in human lymphocytes in vitro.
In the present study, the effect of exposure to ascorbic acid (vitamin C) after gamma-ray-induced chromosomal damage in cultured human lymphocytes was examined to explore the mechanism by which this antioxidant vitamin protects irradiated cells Non-irradiated lymphocytes were exposed to increasing concentrations of ascorbic acid (1-100 micro g/ml) and DNA damage was estimated using chromosomal aberration analysis and the comet assay. The results showed that ascorbic acid did not influence the frequency of chromosomal aberrations in non-irradiated cells, except at the highest concentration (20 micro g/ml), which induced breakage-type chromosomal aberrations. Vitamin C at the concentration of 50 micro g/ml caused DNA damage detected by the comet assay. A significant (34%) decrease in the frequency of chromosomal aberrations was observed in lymphocytes exposed to gamma-radiation and then cultured in the presence of ascorbic acid (1 micro g/ml). The removal of DNA breaks in cells exposed to 2 Gy of gamma-radiation was accelerated in the presence of ascorbic acid as determined by the comet assay, suggesting that it may stimulate DNA repair processes.
Teratog Carcinog Mutagen. 2002;22(6):443-50
Radioprotective-antimutagenic effects of rosemary phenolics against chromosomal damage induced in human lymphocytes by gamma-rays.
The radioprotective effects of carnosic acid (CA), carnosol (COL), and rosmarinic acid (RO) against chromosomal damage induced by gamma-rays, compared with those of L-ascorbic acid (AA) and the S-containing compound dimethyl sulfoxide (DMSO), were determined by use of the micronucleus test for antimutagenic activity, evaluating the reduction in the frequency of micronuclei (MN) in cytokinesis-blocked cells of human lymphocytes before and after gamma-ray irradiation. With treatment before gamma-irradiation, the most effective compounds were, in order, CA > RO > or = COL > AA > DMSO. The radioprotective effects (antimutagenic) with treatment after gamma-irradiation were lower, and the most effective compounds were CA and COL. RO and AA presented small radioprotective activity, and the sulfur-containing compound DMSO lacked gamma-ray radioprotection capacity. Therefore, CA and COL are the only compounds that showed a significant antimutagenic activity both before and after gamma-irradiation treatments. These results are closely related to those reported by other authors on the antioxidant activity of the same compounds, and the degree of effectiveness depends on their structure. Furthermore, the results for treatments before and after gamma-ray irradiation suggest the existence of different radioprotective mechanisms in each case.
J Agric Food Chem. 2006 Mar 22;54(6):2064-8
Radioprotective effect of melatonin assessed by measuring chromosomal damage in mitotic and meiotic cells.
This study was taken to evaluate the radioprotective effects of melatonin. Male adult albino mice were treated (intraperitoneal, i.p.) with 10 mg/kg melatonin either 1 h before or 1/2 h after exposure to 1.5 Gy of gamma-irradiation. Control, melatonin, irradiated and melatonin plus irradiation groups were sacrificed 24 h following treatment. The incidence of micronuclei (MN) in bone marrow cells was determined in all groups. The results show that melatonin caused a significant reduction in micronuclei polychromatic erythrocytes (MNPCE) when animals were treated with melatonin before and not after exposure to radiation. Mitotic and meiotic metaphases were prepared from spermatogonial and primary spermatocytes, respectively. Examination and analysis of metaphases showed no mutagenic effect of melatonin on chromosomal aberration (CA) frequency in spermatogonial chromosomes. Administration of one single dose of melatonin to animals before irradiation lowered total CA from 46 to 32%. However, no significant effect was observed when melatonin was given after irradiation. Similarly, the frequency of CA in meiotic metaphases decreased from 43.5% in the irradiated group to 31.5% in the irradiated group treated with melatonin 1 h before irradiation, but no change was observed when melatonin was administered after irradiation. The data obtained in this study suggest that melatonin administration confers protection against damage inflicted by radiation when given prior to exposure to irradiation and not after, and support the contention that melatonin radioprotection is achieved by its ability as a scavenger for free radicals generated by ionizing radiation.
Mutat Res. 1999 Aug 18;444(2):367-72
Liposoluble antioxidants provide an effective radioprotective barrier.
Ionising radiation causes the massive generation of reactive oxygen species and induces cellular DNA damage. The antioxidant, protective effects of several compounds against gamma-ray-induced chromosomal damage were determined by the micronucleus test, evaluating the reduction in the frequency of micronuclei in cytokinesis-blocked human lymphocytes. The compounds studied were added to human blood at 25 microM, 5 min before or after irradiation with 2 Gy of caesium-137. The results suggest that different protective mechanisms are operating in each case. When the phenolic compounds are added before gamma-irradiation, their protective antimutagenic activity is based on their scavenging capacity against superoxide anion (O(2)(.-)) and, especially, hydroxyl radical ((.)OH), regardless of whether they are oil- or water-soluble compounds. When the phenolic compounds are added after gamma-irradiation treatment, the protective effect relies on activity against reactive oxygen species present in cells, i.e. lipoperoxy radicals (R(-)OO(.)), which are mainly responsible for continuous chromosomal oxidative damage. In addition, ionising radiation enhances lysosomal enzyme secretion and arachidonate release from membranes through lipo-oxygenase, cyclo-oxygenase and phospholipase activities, thus increasing the inflammatory cell response. Only oil-soluble compounds, such as carnosic acid, carnosol and delta-tocopherol, provide a significant protective antimutagenic activity. The most powerful water-soluble antioxidants lack the capacity to protect against gamma-ray-induced damage. The difference between anti-radical and anti-lipoperoxidant activities could explain the different behaviour of the compounds tested in terms of protecting against the lipid peroxidative processes. This anti-lipoperoxidant activity depends on several factors, but it is clear that only the lipo-antioxidants are effective in protecting human cells against oxidative damage, even when administered after exposure to ionising radiation.
Br J Radiol. 2009 Jul;82(979):605-9
Ionizing radiation-induced E-selectin gene expression and tumor cell adhesion is inhibited by lovastatin and all-trans retinoic acid.
E-selectin mediated tumor cell adhesion plays an important role in metastasis. Here we show that ionizing radiation (IR) induces E-selectin gene and protein expression in human endothelial cells at therapeutically relevant dose level. E-selectin expression is accompanied by an increase in the adhesion of human colon carcinoma cells to primary human umbilical vein endothelial cells (HUVEC). The HMG-CoA reductase inhibitor lovastatin impairs IR-stimulated E-selectin expression as analyzed at the level of the protein, mRNA and promoter. Inactivation of Rho GTPases either by use of Clostridium difficile toxin A or by co-expression of dominant-negative Rho blocked IR-induced E-selectin gene induction, indicating Rho GTPases to be essential. Radiation-induced expression of E-selectin was also blocked by all-trans retinoic acid (at-RA), whereas 9-cis retinoic acid was ineffective. Abrogation of IR-stimulated E-selectin expression by lovastatin and at-RA reduced tumor cell adhesion in a dose-dependent manner. Combined treatment with lovastatin and at-RA exerted additive inhibitory effects on radiation-induced E-selectin expression and tumor cell adhesion. Therefore, application of statins and at-RA might have clinical impact in protecting against E-selectin-promoted metastasis, which might arise as an unwanted side effect from radiation treatment.
Carcinogenesis. 2004 Aug;25(8):1335-44
Retinoids and TIMP1 prevent radiation-induced apoptosis of capillary endothelial cells.
Radiation-induced changes in capillaries constitute a basic injury in the pathogenesis of chronic radiation damage to the heart, lung, liver, kidney and brain. It is important to identify new radioprotectors for capillary endothelial cells for use during radiotherapy to minimize normal tissue damage and possibly to increase the deliverable dose. Previously we demonstrated that exposure to ionizing radiation (10 Gy) results in death of bovine adrenal capillary endothelial cells in confluent monolayers by apoptosis. We also showed that retinoids inhibit the growth of endothelial cells, induce their differentiation, down-regulate matrix metalloproteinase (MMP) production, and up-regulate tissue inhibitors of matrix metalloproteinases (TIMPs). In the present studies, we demonstrated that radiation (10 Gy) induced an immediate increase in the amounts and activation of MMP1 and MMP2 in the cell fraction and medium of bovine capillary endothelial cells followed by an incidence of apoptosis. We also obtained data indicating that radiation-induced apoptosis can be inhibited by exposing bovine capillary endothelial cells to all-trans-retinol or all-trans-retinoic acid for 6 days before irradiation, even when the vitamins were removed 24 h before irradiation. Finally, we determined that inhibition of MMPs by TIMP was sufficient to block radiation-induced apoptosis, suggesting that the mechanism of protection by retinoids is through the alteration of levels of MMPs and TIMPs produced by the cells.
Radiat Res. 2004 Feb;161(2):174-84
Antioxidant vitamins C, E, and beta-carotene reduce DNA damage before as well as after gamma-ray irradiation of human lymphocytes in vitro.
The protective effect of vitamins C, E, and beta-carotene against gamma-ray-induced DNA damage in human lymphocytes in vitro was investigated. Cultured lymphocytes were exposed to increasing concentration of these vitamins either before or after irradiation with 2Gy of gamma-rays and DNA damage was estimated using micronucleus assay. A radioprotective effect was observed when antioxidant vitamins were added to cultured cells before as well after irradiation; the strongest effect was observed when they were added no later than 1h after irradiation. The radioprotective effect of vitamins also depended on their concentration; vitamins C added at low concentration (1 microg/ml) before exposure of the cells to radiation prevented induction of micronuclei. Vitamin E at the concentration above 2 microg/ml decreased the level of radiation-induced micronuclei when compared to the cells irradiated without vitamin treatment. beta-Carotene was effective at all tested concentrations from 1 to 5 microg/ml and reduced the number of micronuclei in irradiated cells. The vitamins had no effect on radiation-induced cytotoxicity as measured by nuclear division index. The radioprotective action of antioxidant vitamins C, E, and beta-carotene was dependent upon their concentration as well as time and sequence of application.
Mutat Res. 2001 Apr 5;491(1-2):1-7
Radioprotective role of zinc following single dose radioiodine (131I) exposure to red blood cells of rats.
BACKGROUND & OBJECTIVES: Irradiation with 131I is used for the treatment of various thyroid disorders. It is likely that radioiodine while in systemic circulation may cause some adverse effects on antioxidative enzymes present in red blood cells (RBCs). Zinc, on the other hand, has been reported to maintain the integrity of cells under certain toxic conditions. The present study was conducted to evaluate the adverse effects of 131I on RBCs and also to assess the protection provided by zinc under these conditions. METHODS: Female Wistar rats (n=32) were divided into four groups. Animals in group I served as normal controls; group II animals were administered a dose of 3.7 Mbq of 131I (carrier-free) intraperitoneally, group III animals were supplemented with zinc (227 mg/l drinking water) and animals in group IV were given a combined treatment of zinc as well as 131I. Activities of antioxidant enzymes were assessed in erythrocyte lysates after two days of treatments. RESULTS: An increase in the activity of glutathione reductase (GR), superoxide dismutase (SOD), reduced glutathione (GSH) and malondialdehyde (MDA) in the lysates of erythrocytes was seen after two days of exposure from 131I radiations. However, the activity of catalase was found to be significantly decreased. Interestingly, zinc supplementation to 131I treated rats resulted in attenuating the adverse effects caused by 1,31I on the levels of antioxidative enzymes. INTERPRETATION & CONCLUSION: 131I can induce significant oxidant/antioxidant changes in RBCs and zinc may prove to be a candidate with great promise for radioprotection.
Indian J Med Res. 2005 Oct;122(4):338-42
Zinc as an antiperoxidative agent following iodine-131 induced changes on the antioxidant system and on the morphology of red blood cells in rats.
Iodine-131 ((131)I) irradiation is the first line treatment for Graves’ disease and thyroid carcinoma. In such cases, (131)I gets accumulated in the thyroid, and is released in the form of radioiodinated triiodothyronine (T3) and tetraiodothronine (T4). Various reports describe changes in the blood picture after radioiodine treatment. Zinc, on the other hand, has been reported to maintain the integrity of red blood cells (RBC) under certain toxic conditions. The present study was conducted to evaluate the adverse effects of (131)I on the antioxidant defense system and morphology of RBC and also to assess the possible protection by zinc under irradiation by (131)I. Thirty two female Wistar rats were equally segregated into four main groups. Animals with Group I served as normal controls; Group II animals were administered a dose of 3.7 MBq of (131)I (carrier free) intraperitoneally, Group III rats were supplemented with zinc (227 mg/L drinking water) and Group IV rats were given a combined treatment of (131)I and zinc, in a similar way as in Group II and IV rats. After seven days of (131)I treatment, RBC lysate was prepared and its antioxidant status assessed. The activity of superoxide dismutase (SOD), reduced glutathione (GSH) and malondialdehyde (MDA) in the lysate of RBC was increased. On the contrary, the activity of catalase was found to be significantly decreased. The activity of glutathione reductase (GR) remained unchanged. Marked changes in the shape of RBC from normal discocytes to echinocytes, spherocytes, stomatocytes and acanthocytes were also observed in the blood of the rats treated with (131)I. Zinc supplementation to (131)I treated rats, significantly attenuated the adverse effects caused by (131)I on the levels of MDA, GSH, SOD and catalase. In conclusion, the study revealed significant oxidant/antioxidant changes in RBC following (131)I administration in rats, while zinc was shown to act as a radioprotector agent.
Hell J Nucl Med. 2006 Jan-Apr;9(1):22-6