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

In the present research, we studied the effect of the administration of mel atonin or S-adenosyl-L-methionine (S-AMe) on oxidative stress and hepatic c holestasis produced by double ligature of the extra-hepatic biliary duct (L BD) in adult male Wistar rats. Hepatic oxidative stress was evaluated by th e changes in the amount of lipid peroxides and by the reduced glutathione c ontent (GSH) in lysates of erythrocytes and homogenates of hepatic tissue. The severity of the cholestasis and hepatic injury were determined bq the c hanges in the plasma enzyme activities of alanine aminotransferase (ALT), a spartate aminotransferase (AST), alkaline phosphatase (AP), g-glutamyl-tran speptidase (GGT), and levels of albumin, total bilirubin (TB) and direct bi lirubin (DB). Either melatonin or S-AMe were administered daily 3 days befo re LED, and for 10 days after biliary obstruction. LDB caused highly signif icant increases in plasma enzyme activities and in bilirubin and lipid pero xides levels in erythrocytes and hepatic tissue. Al the same time, this pro cedure produced a notable decrease in the GSH pools in these biological med ia. Both melatonin and S-AMe administration were effective as antioxidants and hepatoprotective substances, although the protective effects of melaton in were superior: it prevented the GSH decrease and reduced significantly t he increases in enzyme activities and lipid peroxidation products produced by biliary ligature. S-AMe did not modify the increased GGT activity nor di d it decrease greatly the TB levels (43% melatonin vs. 14%, S-AMe). However , S-AMe was effective in preventing the loss of GSH in erythrocytes and hep atic tissue, as was melatonin. The obtained data permit the following concl usions. First, the LDB models cause marked hepatic oxidative stress. Second , the participation of free radicals of oxygen in the pathogenecity and sev erity of cholestasis produced by the acute obstruction of the extra-hepatic biliary duct is likely. Third, the results confirm the function of S-AMe a s an antioxidant and hepatoprotector. Finally, melatonin is far more potent and provides superior protection as compared to S-AMe. Considering the dec rease in oxidative stress and the intensity of cholestasis, these findings have interesting clinical implications for melatonin as a possible therapeu tic agent in biliary cholestasis and parenchymatous liver injury.