Effect of phenobarbitone pretreatment on isoniazid-induced lipid changes in plasma, liver and adipose tissue in the rabbit

The subacute effect of a low dose of isoniazid (INH) (10 mg/kg/day for 11 days) in phenobarbitone sodium (PB)-pretreated rabbits (60 mg/kg/day for 4 days) on various lipid parameters in plasma, liver and adipose tissue was investigated. While treatment with PB or INH alone did not alter the lipid levels in plasma and tissues, INH treatment in PB-pretreated rabbits elevated the levels of plasma total lipid and cholesterol. In adipose tissue there was a decrease in total lipid, triglyceride and cholesterol and an elevation in free fatty acid. In contrast, all these parameters were found to be elevated in the liver. It is proposed that the enhanced release of primary amine functional groups from INH during microsomal induction by PB treatment caused increased deposition of lipids in the liver, which is presumably an outcome of enhanced breakdown and mobilization of lipids from the adipose tissue. It is suggested that the assessment of lipid profile would be a useful tool to monitor drug interactions involving INH with hepatotoxic potential.