PROTECTIVE EFFECT OF S-ADENOSYL-L-METHIONINE ON BROMOBENZENE-INDUCED AND D-GALACTOSAMINE-INDUCED TOXICITY TO ISOLATED RAT HEPATOCYTES

The protective effect of S-adenosyl-L-methionine (SAMe) on bromobenzen e (BE)- or D-galactosamine (GaIN)-induced damage to isolated rat hepat ocytes and its effect on cellular glutathione (GSH) levels were invest igated. SAMe at concentrations of 0.5 to 3.0 mmol/L significantly redu ced lactate dehydrogenase leakage from cells exposed to 1.6 mmol/L BE (P <.05 to .001) during 2 hours' incubation, GaIN at 25 to 50 mmol/L i nduced a marked increase of LDH leakage from the cells during the late r stage of 24 hours' incubation and SAMe at 1.0 mmol/L clearly attenua ted the LDH leakage in GaIN (25 mmol/L)-exposed cells. The GSH content in the cells exposed to 2.4 mmol/L BE for 150 minutes was markedly de creased, and further decreased during 24 hours' incubation. SAMe (1.5 mmol/L) both reduced LDH leakage and corrected GSH depletion in cells exposed to 2.4 mmol/L BE. The GSH content in 25 and 50 mmol/L GaIN-exp osed cells was strikingly diminished to 51.2% and 32.8% of the control s, respectively, during 24 hours' of exposure. SAMe at 1.5 mmol/L sign ificantly reduced the loss in GSH content in 25 mmol/L GaIN-exposed ce lls, The findings show that SAMe has beneficial effects on both BB- an d GaIN-induced toxicity to rat hepatocytes. The main mechanism behind the protective effect of SAMe on BE and GaIN toxicity seems to be asso ciated with enhancement of GSH synthesis in the cells.