Qualitative histological study of isoniazid-rifampicin induced liver injury in rats

Objectives: Tuberculosis is still a major public health problem in developing world and in Bosnia and Herzegovina. Treatment of tuberculosis requires a “standard” combination of antituberculotics for a 6-month period. Prolonged use of isoniazid and rifampicin is associated with hepatotoxicity. The pathophysiology of hepatotoxicity is not yet elucidated, and suggested mechanism is oxidative stress. Isoniazid metabolite is considered to be responsible for the tissue damage through formation of free radicals. Methods : Twenty one adult male Wistar rats (210-280 g) were randomized into two groups. In group I (14 rats) animals received rifampicin (50 mg/kg) and isoniazid (50 mg/kg) dissolved in 4 ml/kg isotonic saline. Group II (7 rats) served as control and the animals received 4 ml/kg isotonic saline. The administration was performed intraperitoneally, during 21 days. The animals were sacrificed at the end of that period. Blood samples were obtained for biochemical analysis and liver tissue was processed by histotechnological method. Liver tissue was stained with H&E and PAS method and qualitative histological analysis was performed using light microscopy. Results : Our study revealed changes in liver tissue in the isoniazid-rifampicin treated group including enlargement and swelling of hepatocytes with vacuolization in centrilobular area, dilatation of sinusoids and mononuclear infiltration in portal space. Biochemical analysis of liver enzymes did not show significant difference between groups. Conclusion : In the isoniazid-rifampicin treated group of animals qualitative histological analysis revealed mild changes in liver tissue. Keywords : liver injury, isoniazid, rifampicin, rats, histology