REVERSAL OF ROSIGLITAZONE HEPATOTOXICITY BY SILYMARIN ON RATS

The present study was undertaken to investigate the hepatotoxic potential of rosiglitazone- an oral hypoglycemic thiazolidenedione class of drug. The hepatotoxic potential of rosiglitazone was assessed in-vitro on isolated rat hepatocytes before subjecting to in-vivo studies. The in-vitro activity was measured by trypan blue exclusion assay and determination of liver marker enzymes. The hepatotoxic potential of rosiglitazone was measured at 100 to 500 µg/ml concentration and maximum hepatotoxicity was produced at highest concentration tested. In-vivo hepatotoxic potential of rosiglitazone was assessed on hyperglycemic rats and protective effect of silymarin a known hepatoprotective agent was also tested. When rosiglitazone was administered at the dose of 2 mg/kg body weight for 21 successive days on rats, has produced marked hepatotoxicity when compared to normal animals. The hepatotoxic potential was evaluated by determination of serum biochemical markers and liver anti-oxidant enzyme studies. Hypoglycemic effect of rosiglitazone in presence of silymarin was also assessed in alloxan induced hyperglycemic rats to rule out any drug interaction. The rosiglitazone has produced significant elevation of serum biomarkers when compared to normal animals and the co-administration of silymarin reversed the toxic potential of rosiglitazone. The liver enzyme studies revealed the hepatotoxic potential of rosiglitazone. The co-administration of silymarin has not shown any interaction and rosiglitazone retains its hypoglycemic activity when it was co-administered with silymarin. The study demonstrates that, rosiglitazone induced hepatotoxicity can be reversed by co-administration of a known hepatoprotective agent silymarin without compromising its hypoglycemic potential.