Renoprotective effect of hyperin against CdCl2 prompted renal damage by activation of Nrf-2/Keap-1 ARE pathway in male mice

Abstract

ABSTRACT Objectives: This study explored the mitigating properties of hyperin on renotoxicity induced by cadmium chloride (CdCl2). Methods: Four groups of seven male albino mice each were used in this experiment. Group 1 served as the control, receiving no treatment. Group 2 received daily oral gavage of cadmium chloride (CdCl2) at 0.3 mg/kg body weight for 28 days. Group 3 received both CdCl2 (0.3 mg/kg) and hyperin (100 mg/kg) daily using the same administration method. Finally, Group 4 received only hyperin (100 mg/kg) daily. Results: Cadmium exposure significantly increased kidney dysfunction markers (blood urea nitrogen, creatinine) and oxidative stress (reactive oxygen species, malondialdehyde). Conversely, it decreased antioxidant enzyme activities (glutathione peroxidase, catalase) and glutathione levels. Nuclear factor erythroid 2–related factor 2 and antioxidant gene expression decreased, while Kelch-like ECH-associated protein 1 expression increased. Additionally, cadmium exposure increased inflammatory mediators (nuclear factor kappa B, tumor necrosis factor alpha, interleukin-1β, cyclooxygenase-2) and apoptotic markers (Bax, Caspase-3), alongside decreased Bcl-2 expression and renal tissue abnormalities. Mitochondrial dysfunction manifested with diminished activities of Krebs cycle and respiratory chain enzymes, and reduced mitochondrial membrane potential. Co-treatment with hyperin significantly attenuated these detrimental effects through its anti-apoptotic, antioxidant, and anti-inflammatory properties. Conclusion: Hyperin co-treatment significantly attenuated CdCl2-induced renal damage in mice, suggesting its potential as a protective agent against cadmium-induced kidney toxicity.