EFFECT OF FLUCONAZOLE-QUINOLINE HYBRID ON THE LIVER OF MICE ON ACUTE EXPOSURE TO FLUCONAZOLE QUINOLINE HYBRID

ABSTRACT This study aim to investigate the oxidative stress response in the liver of mice following acute exposure to fluconazole-quinoline hybrid compounds and evaluate the effects on hepatic lipid peroxidation levels and key antioxidant enzyme activities. Forty-five mice (30-45 g, 6-8 weeks old) were randomly divided into five groups (n=9 per group): control group receiving vehicle (DMSO in saline), and three treatment groups receiving fluconazole-quinoline hybrid at 5 mg/kg (TR1), 10 mg/kg (TR2), 15 mg/kg (TR3) and 25 mg/kg (TR3) body weight intraperitoneally for seven consecutive days. Twenty-four hours post-treatment, mice were sacrificed and liver samples were collected for biochemical analyses. Oxidative stress markers including malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) were assessed using enzyme-linked immunosorbent assay (ELISA). Data were analyzed using one-way ANOVA followed by Tukey's post hoc test with significance set at p < 0.05. Contrary to expected patterns of drug-induced hepatotoxicity, all treatment groups showed significantly reduced MDA levels compared to control, with the most pronounced reductions observed in TR1 (4.8 Unit/mg) and TR2 (5.1 Unit/mg) groups, suggesting potential antioxidant properties of the hybrid compound. Catalase activity showed no significant differences between groups (p > 0.05), though the highest activity was recorded in TR1 (3.3 mins), indicating preservation of this critical antioxidant enzyme. Superoxide dismutase activity was significantly increased (p < 0.05) only in the highest dose group TR3 (4.6 μg/mL), suggesting dose-dependent activation of cellular defense mechanisms. However, reduced glutathione levels were significantly depleted (p < 0.05) in the TR3 group (11.5 μmol/g), while other treatment groups showed non-significant reductions compared to control, indicating potential hepatotoxic concerns at higher doses. The fluconazole-quinoline hybrid exhibits a unique hepatic oxidative stress profile characterized by apparent antioxidant effects at lower doses and selective glutathione depletion at higher concentrations. The significant reduction in lipid peroxidation across all treatment groups, combined with maintained catalase activity, suggests the hybrid compound may possess inherent protective properties distinct from conventional hepatotoxic agents. These findings demonstrate that molecular hybridization can result in emergent toxicological properties not predictable from parent compounds alone, emphasizing the need for comprehensive safety evaluation of novel hybrid drug entities. The complex dose-response relationship observed indicates a potentially narrow therapeutic window requiring careful optimization for clinical applications.