Zingerone alleviates cadmium-induced nephrotoxicity in rats via its antioxidant and anti-apoptotic properties

ABSTRACT

Objectives: Cadmium is an essential industrial metal and acts as an environmental toxicant that is a major cause of kidney diseases. Hence, we aimed to evaluate the possible nephroprotective effects of zingerone (ZGO), a major flavonoid constituent in ginger (Zingiber officinale) dry roots, against cadmium-induced nephrotoxicity in rats. Methods: In this study, Wistar albino rats [ACUC HU2020/Z/FMS0120-01] were allocated randomly to 4 groups with seven animals in each group. The control group which received physiological saline; cadmium chloride (CdCl2) treatment group which received CdCl2 at a dose of 6.5 mg/kg intraperitoneally (i.p.) for 7 consecutive days; zingerone treatment group which received 25 mg/kg of zingerone orally for 7 consecutive days and CdCl2(6.5 mg/kg; i.p.)+ZGO (25 mg/kg; p.o.) treatment group which received CdCl2 and ZGO for 7 consecutive days. Results: Co-administration of ZGO along with CdCl2 resulted in a significant reduction in creatinine and urea levels of serum. Additionally, ZGO significantly diminished the tissue levels of Cd concentration, lipid peroxidation, and nitric oxide and significantly recovered the enzymatic and nonenzymatic antioxidant molecules, namely glutathione, total superoxide dismutase, catalase, and glutathione recycling enzymes peroxidase and reductase, in kidney tissue. Furthermore, ZGO treatment prevented the inflammation produced by CdCl2 by restraining the elevation in the level of pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin1beta). Moreover, ZGO improved histopathological alternations in the kidney by preventing apoptosis cascade in kidney tissue by stimulating Bcl-2 and suppressing Bax and caspase-3. Conclusions: Our findings suggest that ZGO has nephroprotective activity in cadmium-induced nephrotoxicity mostly via modulating of oxidant/antioxidant balance, inflammatory response, and apoptosis.