Nephroprotective Potential of Rhamnazin Against Cadmium-Induced Kidney Damages via Activation of Nrf2/Keap1 Pathway

Background/Objective: Cadmium (Cd) is an extremely toxic heavy metal and environmental toxicant, which leads to renal damage by causing oxidative stress. Rhamnazin (RAM) is a novel flavonoid, which possesses multiple pharmacological activities. Therefore, the present study was planned to determine the nephroprotective effects of RAM against Cd-prompted renal toxicity in rats. Methodology: In this investigation, 24 male albino rats were distributed into four equal groups, i.e., control, CdCl2-intoxicated group (2 mgkg(-1)), CdCl2 + RAM-treated group (2 mgkg(-1) + 20 mgkg(-1)), and RAM-only treated group (20 mgkg(-1)). After oral dose administration for 30 days, the alterations in the Nrf2/Keap1 pathway, Cd concentration, antioxidant profile, oxidative stress markers, renal function markers, inflammatory markers, apoptotic markers, and kidney histology were analyzed. Result: The results of the current study revealed that Cd exposure significantly (P < .05) increased Keap1 expression, while decreasing the expressions of Nrf2 and antioxidant genes and level of total antioxidant status (TAS). Additionally, it decreased the activities of antioxidant enzymes. Whereas, the levels of malondialdehyde (MDA), reactive oxygen species (ROS), and total oxidant status (TOS) were increased. Cd exposure increased Cd concentration in tissues. Additionally, it increased the levels of renal function markers, such as urea, urobilinogen, urinary proteins, creatinine, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL). On the contrary, Cd exposure reduced albumin and creatinine clearance. Furthermore, it increased the levels of inflammatory markers in the kidneys. Besides, Cd significantly increased the levels of Bax, caspase-3, and caspase-9, whereas lessened Bcl-2 level. Moreover, adverse histoarchitectural changes were observed following the Cd exposure. However, treatment with RAM significantly restored all the damage in the kidneys of the rats. Conclusion: Our findings highlight the potential of RAM as a valuable therapeutic candidate against heavy metal-induced kidney damage.