Protective Effects of Silymarin in Isoniazid Induced Hepatotoxicity in Rabbits

Abstract

Background:  Isoniazid (INH), first line drug for antitubercular treatment, induces hepatic necrosis in some of human beings in normal doses and in experimental animals in toxic doses. Reactive toxic metabolites of INH are released which disrupt hepatocellular membrane and cause necrosis. So there is a need to find some hepatoprotective and antioxidant agent. Silymarin has been used as a raw extract from the seeds of Silybum marianum (carduimariae fructus) but now mixture of 4 flavonolignane isomers is available i.e. silybinin, isosilybinin, silidianin and silychristin. The data suggests that factor of antioxidation is important in the process of hepatoprotection by silymarin. In this study the role of silymarin against INH induced hepatotoxicity was observed in rabbit model.

Methods:  Study was conducted on oryctolagus cuniculus rabbits (1-1.5 kg) of either sex for a period of 11 days. Four groups of rabbits were formed at random with 6 animals per group. In group I liver function tests were recorded without any drug. In group II effects of silymarin (50 mg/kg/day p.o) was observed. In Group III isoniazid (50 mg/kg /day i.p) was administered. In group IV combined effects of isoniazid and silymarin were observed. Liver function tests including serum bilirubin, ALT and AST were performed on 12^th day. Rabbits were sacrificed on 12^th day for observing histopathological changes in liver.

Results:  In group I, II and IV there was no mortality and rabbits of group II and IV gained weight. Liver architecture remained almost intact in group II. In group III, bilirubin level increased (P<0.05). Histological picture revealed ballooning degeneration, portal inflammation and necrosis of hepatocytes which are signs of acute inflammation. In group IV there was significant improvement in liver architecture when compared with group III. So it can be concluded that INH induced biochemical and histopathological changes are well antagonized by concurrent administration of silymarin for 11days.

Key Words:  Hepatotoxicity, INH-induced hepatotoxicity, Silymarin, Liver function tests.