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 melatonin or S-adenosyl-L-methionine (S-AMe) on oxidative stress and hepatic cholestasis produced by double ligature of the extra-hepatic biliary duct (LBD) in adult male Wistar rats. Hepatic oxidative stress was evaluated by the changes in the amount of lipid peroxides and by the reduced glutathione content (GSH) in lysates of erythrocytes and homogenates of hepatic tissue. The severity of the cholestasis and hepatic injury were determined by the changes in the plasma enzyme activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), g-glutamyl-transpeptidase (GGT), and levels of albumin, total bilirubin (TB) and direct bilirubin (DB). Either melatonin or S-AMe were administered daily 3 days before LBD, and for 10 days after biliary obstruction. LDB caused highly significant increases in plasma enzyme activities and in bilirubin and lipid peroxides levels in erythrocytes and hepatic tissue. At the same time, this procedure produced a notable decrease in the GSH pools in these biological media. Both melatonin and S-AMe administration were effective as antioxidants and hepatoprotective substances, although the protective effects of melatonin were superior; it prevented the GSH decrease and reduced significantly the increases in enzyme activities and lipid peroxidation products produced by biliary ligature. S-AMe did not modify the increased GGT activity nor did 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 hepatic tissue, as was melatonin. The obtained data permit the following conclusions. First, the LDB models cause marked hepatic oxidative stress. Second, the participation of free radicals of oxygen in the pathogenecity and severity of cholestasis produced by the acute obstruction of the extra-hepatic biliary duct is likely. Third, the results confirm the function of S-AMe as an antioxidant and hepatoprotector. Finally, melatonin is far more potent and provides superior protection as compared to S-AMe. Considering the decrease in oxidative stress and the intensity of cholestasis, these findings have interesting clinical implications for melatonin as a possible therapeutic agent in biliary cholestasis and parenchymatous liver injury.
López
P M
PM
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Córdoba, Spain. bb1molop@lucano.uco.es
Fiñana
I T
IT
De Agueda
M C
MC
Sánchez
E C
EC
Muñoz
M C
MC
Alvarez
J P
JP
De La Torre Lozano
E J
EJ
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017734:Bile Ducts, Extrahepatic / Q000601:surgery; D001663:Bilirubin / Q000097:blood; D001651:Cholestasis, Extrahepatic / Q000097:blood* / Q000209:etiology; D005978:Glutathione / Q000097:blood; D008026:Ligation; D008054:Lipid Peroxides / Q000097:blood; D008099:Liver / Q000187:drug effects*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D012709:Serum Albumin / Q000032:analysis; D000637:Transaminases / Q000097:blood
D000975:Antioxidants; D008054:Lipid Peroxides; D012709:Serum Albumin; D012436:S-Adenosylmethionine; D000637:Transaminases; D000469:Alkaline Phosphatase; D005978:Glutathione; D008550:Melatonin; D001663:Bilirubin