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Protocatechuic acid, a natural phenolic compound, has shown to exert beneficial effects against oxidative and inflammatory responses. The study aimed to clarify the nephroprotective activity of protocatechuic acid in LPS\u2010induced acute kidney damage in mice. Forty male Swiss mice were allocated in four groups as follows: normal control group; LPS (250\u2009\u03bcg\/kg, ip)\u2010induced kidney injury group; LPS\u2010injected mice treated with protocatechuic acid (15\u2009mg\/kg, po), and LPS\u2010injected mice treated with protocatechuic acid (30\u2009mg\/kg, po). Significant toll\u2010like receptor 4 (TLR\u20104)\u2010mediated activation of IKBKB\/NF\u2010\u03baB and MAPK\/Erk\/COX\u20102 inflammatory pathways has been observed in kidneys of mice treated with LPS. Oxidative stress was revealed by inhibition of total antioxidant capacity, catalase, nuclear factor erythroid 2\u2010related factor 2 (Nrf2), and NAD(P)H quinone oxidoreductase (NQO1) enzyme along with increased nitric oxide level. In parallel, focal inflammatory effects were shown in between the tubules and glomeruli as well as in the perivascular dilated blood vessels at the cortex affecting the normal morphology of the kidney tissues of LPS\u2010treated mice. However, treatment with protocatechuic acid reduced LPS\u2010induced changes in the aforementioned parameters and restored normal histological features of the affected tissues. In conclusion, our study uncovered that protocatechuic acid has nephroprotective effects in mice with AKI through opposing different inflammatory and oxidative cascades.<\/jats:p>","DOI":"10.1002\/jat.4447","type":"journal-article","created":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T17:54:31Z","timestamp":1676656471000},"page":"1119-1129","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Protocatechuic acid ameliorates lipopolysaccharide\u2010induced kidney damage in mice via downregulation of TLR\u20104\u2010mediated IKBKB\/NF\u2010\u03baB and MAPK\/Erk signaling pathways"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9870-5583","authenticated-orcid":false,"given":"Abeer A. 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