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.
Highlights
Heavy metals toxicity represents a major health problem worldwide
Cadmium chloride administered for 7 days declined extensively (p< 0.05) the body weight of the rats compared to the healthy rats (Figure 1)
The modulatory role of ZGO, to restrain Cd-induced nephrotoxicity, was investigated and discussed that (i) ZGO administration significantly improved Cd-induced kidney injury, as evidenced by decreasing urea and creatinine; (ii) ZGO treatment significantly suppressed Cd caused oxidative stress confirmed by decreasing thiobarbituric acid reactive substances (TBARS) and nitric oxide (NO) and increasing GSH and antioxidant defense system; and (iv) ZGO administration prevented the inflammation and apoptosis in Cd-intoxicated rats by inhibiting the inflammatory markers as TNF-α, IL-1β, Bax, and caspase-3 and enhancing Bcl-2
Summary
Heavy metals toxicity represents a major health problem worldwide. The grown manufacturing pollutions due to fast growth in the human populations have exponentially worsened environmental problems[1]. Conflicts of interest: The authors have no conflict of interest to disclose. The study was carried out at Osmania University, Hyderabad, Telangana State, India.
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