L-deprenyl potentiates cAMP-induced elevation of FGF-2 mRNA levels in rat cortical astrocytes.
Riva MA Molteni R Racagni G
Neuroreport 1997 JUL 7;8(9-10):2165-2168
Riva MA, Hosp San Raffaele, Dibit, Via Olgettina 58, I 20132 Milan, ITALY
THE expression of fibroblast growth factor-2 (FGF-2, basic FGF) is up-regulated in astroglial cells by different stimuli, including glucocorticoid hormones and agents that cause an increase in cyclic AMP (cAMP) levels. In the present study we show ed that L-deprenyl, a drug able to rescue neurons from potentially lethal damage, can potentiate FGF-2 induction by 8Br-cAMP in cultured astrocytes. This effect appears to be independent from its well known inhibitory activity on monoamine oxidase (MAO) t ype B. As astrocyte activation is an important step in response to neuronal injury, our data suggest that potentiation of neurotrophic factor expression may exert neuroprotection and therefore limit the progression of neuronal damage in several pathological situations.
Glutamate toxicity on a PC12 cell line involves glutathione (GSH) depletion and oxidative stress.
Pereira CMF Oliveira CR
Free Radical Biol Med 1997;23(4):637-647
Oliveira CR, Univ Coimbra, Fac Med, Ctr Neurosci Coimbra, P 3000 Coimbra, PORTUGAL
The effect of antioxidants and reducing agents on glutamate-induced cytotoxicity was examined using PC12 cells. The antioxidants vitamin E, idebenone, and selegiline protected cells against the cytotoxicity observed 24 h after exposure to 0.5 or 10 mM glutamate, as determined by lactate dehydrogenase leakage, even when added 3 h after glutamate. The reducing agents, glutathione (GSH) anti dithiothreitol (DTT), also provided protection against the cytotoxicity of glutamate. Preincubation of PC12 cells with the antioxidants mentioned above, or the incubation with those antioxidants after exposure to glutamate for 3 h, prevented the reduction of viability caused by glutamate. Cystine uptake was inhibited by exposure of cells to glutamate, as determined by L-[S-35]-cystine uptake. Incubation of cells with 0.5 or 10 mM glutamate caused a marked decrease in cellular GSH levels, not prevented by antioxidants, The activity of GSSG reductase was decreased by glutamate and this inhibition was reverted in the presence of the reducing agents GSH and DTT. These results indicate that glutamate toxicity on PC12 cells results from the inhibition of cystine uptake with consequent GSH depletion and oxidative stress, suggesting that antioxidants may reduce the cellular damage in pathologic conditions associated with excessive glutamate release. (C) 1997 Elsevier Science Inc.
Influence of selegiline and lipoic acid on the life expectancy of immunosuppressed mice.
Freisleben HJ Neeb A Lehr F Ackermann H
Arzneimittelforschung 1997 JUN;47(6):776-780
Freisleben HJ, Univ Indonesia, Fac Med, Dept Pharmacol & Therapeut, Salemba 6, Jakarta 10430, INDONESIA
Ten groups of 14 immunosuppressed NMRI-mice (nu/nu) were raised and kept under germ-reduced conditions. The control animals were fed a germ-reduced diet, nine other groups received the same diet with selegiline (CAS 14611-51-9, Deprenyl (R)) or lipoic acid (thioctic acid, CAS 62-46-4) admired at various amounts. The 50 % survival rate, the total life span of each group and the areas under the curves were determined to evaluate life expectancy as compared to the controls. The racemate of lipoic acid at high dosage (350 mg/kg body weight) reduced the life span significantly. The S(-)-enantiomer of lipoic acid (75 mg/kg body weight) increased the 50 % survival rate, whereas the physiologic R(+)-enantiomer (9 mg/kg body weight) expanded the total life span of its group. Alteration of only one out of three parameters was not considered significant. All other groups except for one did not differ from controls: only animals which obtained 75 mu g selegiline per kg of body weight and per day exerted increased life expectancies by all three parameters. This group exhibited also in statistical evaluation a significantly (p 0.05) prolongated survival time up to about 200 % as compared to the control animals.