Isoniazid/rifampicin-induced nephrotoxicity in rats: Protective Potential of selenium

Abstract

Background and Objectives: Nephrotoxicity has characterized the use of isoniazid–rifampicin (INH-RIF). Selenium (Se) has potential to protect tissues from damage. This study evaluated the protective activity of Se against INH-RIF-induced nephrotoxicity in rats. Methods: Forty-five adult male albino rats (200-230 g) randomized into nine groups of n = 5 were used. Group A (placebo control) and Group B (solvent control) were treated with normal saline (0.2 mL/day/per oral [p.o]) and corn oil (0.2 mL/day/p.o) for 21 days, respectively. Groups C–E were treated with Se (0.1, 0.2, and 0.4 mg/kg/day/p.o, respectively) for 21 days. Group F was treated with INH-RIF (50/100 mg/kg/day/p.o) for 21 days. Groups G–I were supplemented with Se (0.1, 0.2, and 0.4 mg/kg/day/p.o, respectively) before treatment with INH/RIF (50/100 mg/kg/day/p.o) for 21 days. After treatment, the rats were anesthetized. Blood samples were collected and evaluated for serum renal function markers (creatinine, urea, uric acid, total protein, and albumin). Kidneys were assessed for histology, malondialdehyde (MDA), and antioxidants (superoxide dismutase, glutathione, catalase, and glutathione peroxidase). Results: Body weight was decreased whereas kidney weight was increased significantly (P < 0.01) in INH-RIF-treated rats when compared to control. INH-RIF caused significant (P < 0.001) increases in serum renal function markers and kidney MDA level when compared to control. INH-RIF caused significant (P < 0.001) decreases in kidney antioxidants when compared to control. Kidneys of INH-RIF-treated rats showed tubular necroses and widened Bowman's space. INH-RIF-induced nephrotoxicity was significantly reduced in a dose-dependent fashion in rats supplemented with Se (0.1, 0.2, and 0.4 mg/kg) at P < 0.05, P < 0.01, and P < 0.001, respectively, when compared to INH-RIF. Se may clinically protect against INH-RIF-induced nephrotoxicity. Conclusion: This study showed that Se may clinically prevent INH-RIF-related nephrotoxicity.