Effects of silymarin MZ-80 on hepatic oxidative stress in rats with biliary obstruction.
This study was designed to evaluate the effects of three pharmaceutical forms of silymarin (silymarin MZ-80, silybinin-beta-cyclodextrin, and silybinin) on the liver oxidative status in vitro and after oral administration to rats with extrahepatic biliary obstruction (EBO) and sham-operated animals. We evaluated thiobarbituric acid-reactive substances (TBARS), glutathione (GSH + GSSG) and their related enzyme activities (GSH peroxidase, GSSG reductase and GSH transferase). All three compounds inhibited the in vitro production of TBARS (IC(50) 56-533 micromol/l). These compounds, mainly silymarin MZ-80, also increased GSH peroxidase and GSH transferase activities. In EBO rats we found increases in TBARS production which was inhibited by 50-70% after treatment. Glutathione was reduced by 55% and elevated by silymarin MZ-80. GSH transferase increased in the group given silymarin MZ-80. We conclude that all three derivatives of silymarin show a clear ability to reduce lipid peroxidation in the liver. Silymarin MZ-80 was the only compound that enhanced the glutathione antioxidant system.
González-Correa
J A
JA
Department of Pharmacology and Therapeutics, School of Medicine, University of Málaga, Spain.
de la Cruz
J P
JP
Gordillo
J
J
Ureña
I
I
Redondo
L
L
Sánchez de la Cuesta
F
F
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001651:Cholestasis, Extrahepatic / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012838:Silymarin / Q000031:analogs & derivatives / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D012838:Silymarin; D017392:Thiobarbituric Acid Reactive Substances; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase