Mitigative effects of didymin against cadmium-induced renal injury via regulating Nrf-2/Keap-1, apoptosis, inflammation and oxidative stress

Cadmium (Cd) is a toxic heavy metal present in environment that has the potential to instigate renal toxicity. Didymin (DDM) is a natural flavone, which shows anti-oxidant, anti-inflammatory and antiapoptotic nature. Therefore, the current study was formulated to appraise the attenuative potential of DDM against Cd instigated nephrotoxicity. Forty‐eight albino rats were divided into four equal groups, including control, Cd (5mg/kg) inebriated group, Cd + DDM (5mg/kg + 1mg/kg) concurrent-treated group, as well as DDM (1mg/kg) alone treated group. The trial was conducted for 30 days and the rats were anesthetized, decapitated and further analyses were performed. The results demonstrated that Cd treatment lowered the expressions of Nrf-2 and its anti-oxidant genes while escalating Keap-1 expression. Cd exposure downregulated the activities of antioxidant enzymes, SOD, GSR, CAT, HO‐1, GPx, GST & GSH contents, while the levels of MDA and ROS were escalated. Furthermore, Cd exposure lowered the levels of creatinine clearance and albumin, while increasing the levels of urobilinogen, urinary proteins, urea, creatinine, NGAL and KIM-1 levels. Moreover, Cd intoxication also augmented the levels of inflammatory indices including, IL-1β, NF-κB, TNF-α, IL-6 and COX-2 activity. Additionally, Cd exposure reduced the expressions of Bcl-2, while increasing Bax and caspase-3 expressions. In addition to this, Cd also provoked multiple histological injuries in the renal tissues of the rats. However, DDM supplementation markedly recovered the renal tissues from the Cd induced damages. In conclusion, DDM protected the renal tissues from Cd-provoked damages due to its antiapoptotic, anti-oxidant and anti-inflammatory efficacy. [Display omitted] •Cadmium dysregulated the expressions of Nrf-2/Keap-1 and apoptotic markers.•Cadmium altered the activities of antioxidant enzymes and induced oxidative stress.•Cadmium increased the levels of renal function markers and inflammatory markers.•Cadmium disturbed renal histopathological architecture.•Didymin supplementation recovered all the above-mentioned disturbances.