{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:17:45Z","timestamp":1790770665380,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T00:00:00Z","timestamp":1601424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cyclophosphamide (CP) is a chemotherapeutic agent which is extensively used in the treatment of multiple neoplastic and nonneoplastic diseases like breast cancer, lymphomas, systemic lupus erythematosus, and multiple sclerosis. Dose\u2010limiting side effects, mainly nephrotoxicity is a major problem hindering its use in the clinical practice. CP induces nephrogenic syndrome of inappropriate antidiuresis mostly via the activation of arginine vasopressin V<jats:sub>2<\/jats:sub> receptors. Moreover, CP produces reactive metabolites which is responsible for augmentation of lipid peroxidation and oxidative stress. Tolvaptan (TOL) is a selective vasopressin V<jats:sub>2<\/jats:sub> receptor antagonist used in the treatment of clinically significant hyponatremia, volume overload in heart failure, and liver cirrhosis with edema. The present study aimed to investigate the potential protective effect of TOL in CP\u2010induced nephrotoxicity. Twenty\u2010four adult male albino rats were randomly divided into four groups: the control group, TOL group that treated daily with tolvaptan (10\u00a0mg\/kg\/d, orally), CP group where CP was administered intraperitoneally 75\u00a0mg\/kg on days 3, 4, 5, 19, 20, and 21 of study, and the CP\u00a0+\u00a0TOL group where animals were treated with TOL daily with (10\u00a0mg\/kg\/d, orally) for 22\u00a0days with concomitant administration of CP as described before. Coadministration of TOL with CP induces significant improvement in the level of urine volume, serum Na+, serum osmolarity, urinary creatinine, and free water clearance in addition to significant reduction of body weight, serum creatinine, urea, serum K+, blood pressure, urine osmolarity, and the fractional excretion of sodium as compared to CP\u2010treated group. In addition, coadministration of TOL significantly reduced MDA, the marker of lipid peroxidation, and different pro\u2010inflammatory cytokines. Histopathological changes showed improvement in the signs of nephrotoxicity with the coadministration of TOL. Also, co\u2010treatment with TOL significantly decreased the level of markers of apoptosis as caspase\u20103 and Bax with increased expression of antiapoptotic Bcl\u20102 in renal tissue as compared to CP\u2010treated group.<\/jats:p>","DOI":"10.1002\/prp2.659","type":"journal-article","created":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T11:39:53Z","timestamp":1601465993000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Protective effect of tolvaptan against cyclophosphamide\u2010induced nephrotoxicity in rat models"],"prefix":"10.1002","volume":"8","author":[{"given":"Mohamed","family":"El\u2010Shabrawy","sequence":"first","affiliation":[{"name":"Department of Medical Pharmacology Faculty of Medicine Cairo University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"Mishriki","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology 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