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

OBJECTIVES

This study explored the mitigating properties of hyperin (HYP) on renotoxicity induced by cadmium chloride (CdCl).

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 CdCl at 0.3 mg/kg body weight for 28 d. Group 3 received both CdCl (0.3 mg/kg) and HYP (100 mg/kg) daily using the same administration method. Finally, Group 4 received only HYP (100 mg/kg) daily.

RESULTS

Cd exposure significantly increased kidney dysfunction markers (blood urea nitrogen and creatinine) and oxidative stress (reactive oxygen species [ROS] and malondialdehyde [MDA]). Conversely, it decreased antioxidant enzyme activities (glutathione peroxidase (GPx] and catalase [CAT]) and glutathione (GSH) levels. Nuclear factor erythroid 2-related factor 2 (Nrf-2) and antioxidant gene expression decreased, while Kelch-like ECH-associated protein 1 expression increased. Additionally, Cd exposure increased inflammatory mediators (nuclear factor kappa B, tumor necrosis factor alpha [TNF-α], interleukin-1β [IL-1β], and cyclooxygenase-2) and apoptotic markers (Bax and 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 HYP significantly attenuated these detrimental effects through its anti-apoptotic, antioxidant, and anti-inflammatory properties.

CONCLUSION

HYP co-treatment significantly attenuated CdCl-induced renal damage in mice, suggesting its potential as a protective agent against Cd-induced kidney toxicity.