S-Adenosyl-L-Methionine Prevents Intracellular Glutathione Depletion by GSH-Depleting Drugs in Rat and Human Hepatocytes

Abstract

SummaryThis study examines the ability of externally added S-adenosyl-L-methionine (SAMe) to act as a precursor of intracellular glutathione (GSH) and to prevent the GSH depletion induced by paracetamol, opiates and ethanol in rat and human hepatocytes.Incubation of rat or human hepatocytes with SAMe 100 I'moljL as the only sulphur source in the medium resulted in a time-dependent elevation of intracellular GSH. Pretreatment of hepatocytes with SAMe resulted in a significant decrease in the cytotoxicity produced by exposure to paracetamol, heroin, methadone or ethanol, when compared with cultures not pretreated with SAMe. Preincubation of rat and human hepatocytes with SAMe attenuated the GSH depletion caused by paracetamol, heroin and methadone. In addition, the decrease in GSH resulting from exposure of hepatocytes to ethanol 50 mmol/L was prevented when SAMe was simultaneously added to cultures.These experimental results provide direct evidence that exogenously administered SAMe increases intracellular GSH levels in rat and human hepatocytes and prevents the GSH depletion caused by paracetamol, opiates and ethanol.

Protective effect of melatonin against oxidative stress induced by ligature of extra‐hepatic biliary duct in rats: comparison with the effect of S‐adenosyl‐l‐methionine

“…We have already mentioned that the main metabolic functions ascribed to S-MAe, among which are restoration and increases in hepatic GSH reserves, are worth noting. During hepatic oxidative stress, a decrease in the S-AMe-synthetase activity is usual; this leads to the oxidation of the SH groups in the enzyme [Pisi and Marchesini, 1990;Jover et al, 1992]. Such a phenomenon creates the following vicious cycle: low concentrations of GSHoxidative stressincrease in the inhibition of S-AMe-synthetase marked reduction in GSH reserves.…”

Perifusion of co-cultured hepatocytes: optimization of studies on drug metabolism and cytotoxicity in vitro

“…The protective effect of S-adenosylmethionine against menadione cytotoxicity may be explained by its ability to prevent glutathione depletion (Friedel et al, 1989;Jover et al, 1992). Interestingly, in stationary cultures the presence of or the pretreatment with S-adenosylmethionine resulted in a shift of the cytotoxic concentrations for menadione to only slightly higher values.…”

Effects of S-adenosylmethionine on intrabiliary glutathione degradation induced by long-term administration of cyclosporin A in the rat

“…S-adenosylmethionine (SAMe) is a thiolic compound that plays an important role in transmethylation and transsulphuration reactions. SAMe has been reported to prevent and reverse the cholestasis and hepatotoxicity associated with several drugs and chemical compounds, either by normalizing membrane fluidity through methylation of membrane phospholipids or by maintaining the hepatic pool of glutathione (Corrales et al, 1992;Jover et al, 1992). We have previously shown that SAMe cotreatment protects against glutathione depletion, changes in hepatocyte membrane fluidity and composition, and abnormalities in biliary bile acid, lipid and protein secretion induced by CyA (Fernández et al, 1995;Galán et al, 1995).…”