Comparative safety assessment of itraconazole and terbinafine with co-administration of quercetin in rats

Abstract

The present study was conducted to evaluate the comparative safety assessment of itraconazole and terbinafine with or without co-administration of quercetin in female Wistar albino rats. Forty-eight rats were divided in to six groups (n=8), with Group I, which served as control, received single dose of normal saline. Group II, III, IV, V and VI rats were administered with quercetin (20 mg/kg), itraconazole (30 mg/kg), terbinafine (20 mg/kg), itraconazole @ 30 mg/kg + quercetin @ 20 mg/kg and terbinafine @ 20 mg/kg + quercetin @ 20 mg/kg respectively through oral gavage for 28 days. Blood samples collected on day 0, 14 and 28 were subjected to haematological and biochemical analysis. On day 29, liver and kidney tissue samples from sacrificed rats were examined for gross and histopathological changes. Group III and IV rats exhibited reduced body weight gain, rough hair coat, lethargy and anorexia, while group III rats showed significantly (p?0.05) elevated alanine aminotransferase (ALT), and aspartate aminotransferase (AST), levels as compared to group IV, indicating itraconazole to be more hepatotoxic than terbinafine. The hepatoxicity was evident with the gross pathology and the histopathology of liver. Co-administration of quercetin in groups V and VI had significantly (p?0.05) restored the biochemical parameters, possibly indicating the ameliorating effect of quercetin on the hepatic damage, which was correlated positively with the histopathological findings of liver in Group V and VI. The study concluded that co-administration of quercetin with itraconazole and terbinafine had hepatoprotective effects, possibly being attributed to its antioxidant, prooxidant, antiapoptotic and anti-inflammatory properties. Thus, quercetin could be an option with antimicrobial agents for the synergistic or hepatoprotective effects in clinical situations.