Journal
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
Volume 29, Issue 38, Pages 57591-57602Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s11356-022-19876-7
Keywords
Nephropathy; Kaempferol; CdCl2; Kidney; Oxidative stress; Inflammation; NE-kappa B; Nrf2
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Funding
- King Khalid University, Abha, KSA [R.G.P2/35/43]
- Taif University, Taif, Saudi Arabia [TURSP-2020/99]
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This study demonstrates that kaempferol has a nephroprotective effect against cadmium-induced nephropathy by reducing kidney damage, improving kidney function, and attenuating oxidative stress and inflammation. It achieves these effects by suppressing NF-kappa B p65 and activating Nrf2.
This study evaluated the nephroprotective effect of kaempferol against cadmium chloride (CdCl2) -induced nephropathy in rats. It also investigated if activation of Nrf2 is a common mechanism of action. Adult male rats ((150 +/- 15 g) were divided into 4 groups (n = 8/each) as a control (1% DMSO, orally), control + kaempferol (200 mg/kg, orally), CdCl2 (50 mg/l in drinking water), and CdCl2 + kaempferol (200 mg/kg)-treated rats. All treatments were conducted for 8 weeks. Kaempferol significantly attenuated CdCl2-induced weight loss, reduction in kidney weights, and the injury in the glomeruli, proximal tubules, and distal tubules in the treated rats. It also significantly lowered serum levels of urea and creatinine, increased urine output and urinary creatinine levels and clearance but reduced urinary levels of albumin urinary albumin exertion (UAER), and urinary albumin/creatinine ratio (UACR) in these rats. In parallel, kaempferol downregulated renal levels of cleaved caspase-3 and Bax and unregulated those of Bcl2. In the kidney tissues of the control animals and CdCl2 rats, kaempferol significantly attenuated oxidative stress, inflammation and significantly boosted levels of manganese superoxide dismutase and glutathione. Also, and in both groups, kaempferol suppressed the nuclear levels of NF-kappa B p65, downregulated Keapl, and stimulated the nuclear activation and protein levels of Nrf2. In conclusion, kaempferol is a potential therapeutic drug to prevent CdCl2 -induced nephropathy due to its anti-inflammatory and anti-oxidant effects mediated by suppressing NF-NF-kappa B p65 and transactivating Nrf2.
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