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

BACKGROUND

Cadmium (Cd) is a toxic heavy metal present in environment that has 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 attenuative potential of DDM against Cd instigated nephrotoxicity.

METHODS

Forty-eight albino rats were divided into four equal groups, including control, Cd (5 mg/kg) inebriated group, Cd + DDM (5 mg/kg + 1 mg/kg) concurrent-treated group, as well as DDM (1 mg/kg) alone treated group. The trial was conducted for 30 days and then the rats were anesthetized, decapitated and further analyses were performed.

RESULTS

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. Moreover, Cd intoxication also augmented the levels of inflammatory indices including, IL-1β, NF-κB, TNF-α, IL-6 and COX-2. 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.

CONCLUSION

In conclusion, DDM protected the renal tissues from Cd-provoked damages due to its antiapoptotic, anti-oxidant and anti-inflammatory efficacy.