Influence of silymarin administration on hepatic glutathione-conjugating enzyme system in rats treated with antitubercular drugs.
OBJECTIVE
This study evaluated the influence of simultaneous administration of silymarin (SIL), a hepatoprotective and antioxidant agent, on the status of glutathione (GSH) and its metabolising enzymes in the liver tissue of rats treated with antitubercular drugs, i.e. isoniazid (INH), rifampicin (RIF) and pyrazinamide (PYR).


METHODS
Male Wistar albino rats (n = 24) were randomly divided into four groups. Group I received saline as they served as controls. Group II rats were administered antitubercular drugs (INH 25 mg/kg + RIF 50 mg/kg + PYR 140 mg/kg orally) daily for 45 days. Group III animals were treated with SIL (50 mg/kg orally) simultaneously with the antitubercular drugs for the same period. Group IV animals were treated with SIL alone. The status of GSH, glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-s-transferase (GST) in liver tissue was evaluated at the end of the study.


RESULTS
Administration of antitubercular drugs caused a significant decrease (p < 0.001) in the status of GPx, GST and GR and of non-enzymic (GSH) antioxidants in liver tissue when compared with saline-treated control rats. Simultaneous treatment of SIL with antitubercular drugs completely prevented decreases in the levels of all the above parameters. Treatment with SIL alone enhanced the activities of GST (p < 0.001) and GPx (p < 0.05) and did not alter glutathione levels compared with control.


CONCLUSIONS
A fall in the status of glutathione and its conjugating enzymes upon administration of antitubercular drugs denotes an impairment of the antioxidant defence mechanism. Simultaneous administration of SIL afforded complete protection of the liver against this abnormality, an effect that could have been due to the strong antioxidant properties of SIL.
Victorrajmohan
Chandrasekaran
C
Department of Pharmacology and Environmental Toxicology, Dr ALM Postgraduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, India.
Pradeep
Kannampalli
K
Karthikeyan
Sivanesan
S
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000517:prevention & control; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012838:Silymarin / Q000008:administration & dosage / Q000494:pharmacology*
D000975:Antioxidants; D000995:Antitubercular Agents; D012838:Silymarin; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione