Effects of chronic administration of S-adenosyl-L-methionine on brain oxidative stress in rats

S-adenosyl-L-methionine (SAM), used to treat liver diseases and as a coadju vant in antidepressive medication, has neuroprotective effects in animal mo dels. The aim of this study was to discover whether SAM has antioxidant eff ects in rat brain tissue. Ten male Wistar rats were killed by decapitation and the forebrains incubat ed with SAM for in vitro experiments. To study the effects of long-term adm inistration, animals in four groups of ten rats each were given 10 mg SAM/k g per day s.c., and 40 other rats were given an equivalent volume of L-lysi ne (the commercial solvent for SAM). Treatment was started at the end of la ctation, and animals were killed by decapitation after 15 days or 1, 6 or 2 2 months of treatment. The forebrain of each animal was used to test membra ne lipid peroxidation by determining thiobarbituric acid-reactive substance s (TBARS), glutathione level and enzyme activities related to glutathione ( reduced form GSH, oxidized form GSSG) metabolism: GSH-peroxidase (GSHpx), G SSD-reductase (GSSGrd) and GSH-transferase (GSHtf). Chronic treatment with SAM decreased maximum forebrain production of TEARS by 46% compared with animals given L-lysine and increased glutathione level s by 50%, GSHpx activity by 115% and GSHtf activity by 81.4%. The results o f in vitro experiments were qualitatively similar: lipid peroxidation was i nhibited (13.1+/-1.3 nmol/mg protein in controls vs. 5.9+/-0.8 nmol/mg prot ein in samples incubated with 1000 mu mol/l SAM) and glutathione levels wer e stimulated (0.97+/-0.06 mu mol/g tissue in control samples vs. 1.55+/-0.0 8 mu mol/g tissue in samples incubated with 1000 mu mol/l SAM), as were GSH px and GSHtf. No significant effect was seen in any of the experiments with L-lysine. We conclude that SAM has antioxidant effects in rat brain tissue both in vitro and ex vivo. The effect is seen both as inhibition of lipid peroxide production and as an enhancement of the endogenous glutathione ant ioxidant system.