@article {Guada58, author = {Melissa Guada and Raghu Ganugula and Manicka Vadhanam and Majeti N.V. Ravi Kumar}, title = {Urolithin A Mitigates Cisplatin-Induced Nephrotoxicity by Inhibiting Renal Inflammation and Apoptosis in an Experimental Rat Model}, volume = {363}, number = {1}, pages = {58--65}, year = {2017}, doi = {10.1124/jpet.117.242420}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Cumulative kidney toxicity associated with cisplatin is severe and there is no clear consensus on the therapeutic management of the same. The pathogenesis involves activation of inflammatory and apoptotic pathways; therefore, regulating these pathways offers protection. Given the anti-inflammatory and antioxidant effects of urolithin A, a gut microbial metabolite of ellagic acid, our aim was to explore the potential use of urolithin A in the prevention of cisplatin-induced nephrotoxicity in an experimental rat model. For this purpose, animals received a single intraperitoneal dose of cisplatin (5 mg/kg body weight). Six hours prior to cisplatin administration, rats were orally treated with either ellagic acid or urolithin A (50 mg/kg body weight), followed by a daily dose of these compounds during the next 5 days. At the end, plasma and kidneys were collected for analysis. Cisplatin-induced kidney damage was revealed by a significant rise in the plasma creatinine levels accompanied by significant morphologic changes in tubules, T cell Ig and mucin domain-containing protein-1, ionized calcium-binding adapter molecule 1, as well as a marked increase in the number of apoptotic cells localized in tubules. Cisplatin also reduced nitric oxide synthase 3 and nuclear factor kappa-light-chain-enhancer of activated B cells resulting in regulation of various inflammatory cytokines. Urolithin A effectively attenuated cisplatin-induced kidney damage and showed significantly greater effect than its precursor ellagic acid on preserving the normal kidney architecture by downregulating the proinflammatory cytokines. In summary, urolithin A mitigates cisplatin-induced nephrotoxicity in rats by modulation of the inflammatory cascade and inhibition of the proapoptotic pathway.}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/363/1/58}, eprint = {https://jpet.aspetjournals.org/content/363/1/58.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }