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Protective Effect of Urolithin a on Cisplatin-Induced Nephrotoxicity in Mice via Modulation of Inflammation and Oxidative Stress

Protective Effect of Urolithin a on Cisplatin-Induced Nephrotoxicity in Mice via Modulation of Inflammation and Oxidative Stress

Taile Jing, Jiezhi Liao, Kezhen Shen, Xiaoyi Chen, Zhijie Xu, Wenjun Tian, Yimin Wang, Baiye Jin, Hao Pan

Food Chem Toxicol. 2019 Jul;129:108-114.

PMID: 31014901

Abstract:

Limitation of widely used anti-cancer agent cisplatin for a patient is nephrotoxicity. Nephrotoxicity is presentable in mice by injecting cisplatin at 25 mg/kg with 3 days endpoint. We used the same model to understand the protective role of urolithin A. Cisplatin-induced renal damages measured by histological damage in proximal tubular cells and by the increase in serum neutrophil gelatinase-associated lipocalin (NGAL), blood urea nitrogen (BUN), creatinine and urinary Kidney Injury Molecule-1 (KIM-1). Urolithin A pretreatment reduced all the above renal damage parameters in a significant way. Urolithin A attenuated cisplatin-induced pro-inflammatory cytokine/chemokine tumor necrosis factor α (TNFα), interleukin 23 (IL-23), interleukin 18 (IL-18) and macrophage inflammatory protein 2 (MIP2). Cisplatin-induced CD11b positive macrophages in kidneys reduced by urolithin A. Urolithin A also attenuated cisplatin-induced renal oxidative/nitrative stress, which was measured by lipid peroxidation(4-hydroxy-2-nonenal or 4-HNE protein adducts) and protein nitration. Urolithin A cisplatin-induced kidney injury in mice through the down regulation of inflammatory cytokines/chemokine, immune cells, and oxidative/nitrative stress thus improving cisplatin-induced proximal tubular cell death.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1143700	Urolithin A		1143-70-0	Price

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