Effect of the new anti-ischaemic drug "trimetazidine" on hepatic injury caused by carbon tetrachloride in rats

ABSTRACT

The effects of trimetazidine, a novel anti-ischaemic agent, on the development of hepatic injury induced in rats with carbon tetrachloride, were investigated. Hepatotoxicity was induced by CCl[4] orally [0.2 ml/kg followed by 0.1 ml/kg after one week]. Trimetazidine at three dose levels [3.6, 7.2 and 14.4 mg/kg], silymarin [25 mg/kg] and combination of trimetazidine [7.2 mg/kg] and silymarin [25 mg/kg] were administered orally daily for 15 days, starting at time of administration of CCL. The daily administration of trimetazidine conferred significant protection against the hepatotoxic effects of CCL, in rats. It decreased the increases in serum alanine aminotransferase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase [ALP] and also prevented the development of hepatic necrosis caused by CCL as determined 15 days after drug administration. Thus, compared with the CCL control group, serum ALT decreased by 35.1, 49.5 and 57%, AST by 28.2, 31.6 and 36% and ALP by 32, 39.7 and 40.6%, after the administration of trimetazidine at 3.6, 7.2 and 14.4 mg/kg, respectively. Silymarin administered alone, at the dose of 25 mg/kg reduced serum ALT by 30%, AST by 29.1% and ALP by 38.4% compared to CCL control. When silymarin was combined with 7.2 mg/kg of trimetazidine, the activities of ALT, AST and ALP were markedly decreased by 47.2%, 47.2% and 50.6%, respectively, compared with the CCl[4]control, indicating a beneficial additive effect. Histopathologic examination of the liver of rats treated with CCl[4] + trimetazidine showed less fibrosis compared with the CCl[4] -control group. Co-treatment with silymarin and trimetazidine, on the other hand resulted in marked histologic protection. It is concluded that the anti-ischaemic agent trimetazidine lessened hepatocellular injury caused by CCl[4], in rats, and had additive effect with silymarin. It was suggested, therefore, that trimetazidine alone or in combination with silymarin might have a place in the therapy of chronic liver diseases