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The current investigation studied the possible protective effects of calcitriol on cisplatin-induced hepatorenal toxicity. Mice were divided randomly as follows: control group, calcitriol group (received calcitriol 5\u2009\u00b5g\/kg, p.o. for 14\u2009days), cisplatin group (received a single i.p. injection of cisplatin 10\u2009mg\/kg on the 10th day), and calcitriol\u2009+\u2009cisplatin group (received calcitriol 5\u2009\u00b5g\/kg, p.o. for 14\u2009days and cisplatin 10\u2009mg\/kg, i.p. on the 10th day). The possible interaction between calcitriol and cisplatin on cell viability was tested in HepG2 cells by MTT assay. Hepatorenal toxicity induced by cisplatin was reversed by calcitriol, as evidenced by improved histological examinations and liver and kidney function tests. In addition, calcitriol counteracted oxidative stress and enhanced Nrf2 and Mrp2 expression in the liver and kidney while suppressing levels of p38 MAPK in cisplatin-treated mice. Calcitriol also inhibited cisplatin-induced hepatic and renal inflammation, as determined by suppressing TNF-\u03b1 and enhancing IL-10 levels. By downregulating caspase-3, calcitriol also promoted liver and kidney tissue survival in mice treated with cisplatin. Moreover, cisplatin\u2019s cytotoxic effects were significantly potentiated when calcitriol was combined with cisplatin. The current study showed that calcitriol protects against cisplatin-induced hepatorenal injury by suppressing oxidative stress, inflammation, and apoptosis, which the Nrf2-Mrp2\/p38 MAPK pathway might regulate.<\/jats:p>","DOI":"10.1177\/03946320241306276","type":"journal-article","created":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T00:40:28Z","timestamp":1734396028000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["Calcitriol ameliorates cisplatin-induced hepatorenal toxicity via regulation of Nrf2-Mrp2\/p38 MAPK signaling in mice"],"prefix":"10.1177","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6752-9094","authenticated-orcid":false,"given":"Mohamed A","family":"Morsy","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Hofuf, Al-Ahsa, Saudi Arabia"},{"name":"Department of Pharmacology, 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