Protective effect of urolithin a on cisplatin-induced nephrotoxicity in mice via modulation of inflammation and oxidative stress.

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.

Anticarcinogenic effect of Umbelliferone in human prostate carcinoma: An in vitro study.

PURPOSE: To explore the chemoprotective effect of umbelliferone (UF) on prostate cancer cell lines, i.e. primary stage (LnCap) and last stage (PC3) prostate cancer together with the effect on the induction of apoptosis and alteration on cell cycle arrest. METHODS: Various concentrations of UF were evaluated against the different prostate cancer cell lines. Lipopolysaccharide (LPS) induced cytokines related factor profiling, proinflammatory cytokines, and inflammatory mediators were studied using Western blot analysis. RESULTS: UF showed significant apoptotic effect. Moreover, treatment with UF did not show apoptosis or cell cycle arrest on the non-cancerous cells including BHP-1, suggesting a selective tumor cell specific effect. UF treatment also enhanced the expression of Bax in PC3 cells, but had no significant effect on the activation of nuclear factor κB (NF-κB). Thus, the apoptosis induction was independent of NF-κB activation. CONCLUSION: The results of the present investigation confirmed the chemoprotective effect of UF in early-stage (Ln- Cap) and late-stage (PC3) prostate cancer cells.