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Protective effect of urolithin a on cisplatin-induced nephrotoxicity in mice via modulation of inflammation and oxidative stress
- Jing, Taile, Liao, Jiezhi, Shen, Kezhen, Chen, Xiaoyi, Xu, Zhijie, Tian, Wenjun, Wang, Yimin, Jin, Baiye, Pan, Hao
- Food and chemical toxicology 2019 v.129 pp. 108-114
- blood serum, cell death, chemokines, cisplatin, creatinine, histology, inflammation, interleukin-18, interleukin-23, kidneys, lipid peroxidation, macrophages, mice, models, nephrotoxicity, neutrophils, oxidative stress, patients, protective effect, toxicology, tumor necrosis factor-alpha, urea nitrogen
- 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.