Effect of trimethoprim administration on hepatic functions of albino rats

The effects of chronic and high-dose administration of trimethoprim (TMP) i.p. for different periods on serum and hepatic functions of rats were studied at cellular and subcellular levels. Most of the parameters studied were unaffected after chronic administration of TMP (10 mg/kg/day) for 90 days except an increase in total lipid content of liver and liver microsomes. Administration of TMP in doses of 40 mg and 80 mg/kg/day for 21 days caused a significant increase in total lipid, cholesterol and transaminases activities of serum and liver. Protein, RNA and phospholipid contents of liver and microsomes decreased significantly while DNA content remained unchanged. Glycogen content of liver decreased significantly but alkaline phosphatase activity did not show any noticeable alteration. Histopathological findings showed fatty infiltration and distorted liver architecture. Administration of TMP in doses of 40 mg and 80 mg/kg/day for 14 days changed all the parameters and enzymes in a similar pattern but with less intensity. From the present study it is obvious that high doses of this drug cause harmful toxic effects on serum and hepatic function with liver injury whereas chronic administration has no effect so far.