{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T15:41:28Z","timestamp":1784043688008,"version":"3.55.0"},"reference-count":69,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Cyclophosphamide (CYC) is an effective chemotherapeutic agent and immunosuppressant drug. Former research showed that CYC induces testicular toxicity through oxidative stress, inflammation and apoptosis. Saroglitazar (SAR) is a dual PPAR\u03b1\/\u03b3 agonist, used for treatment of diabetic dyslipidemia. Purpose: This study aimed to elucidate the protective impact of SAR against CYC-linked testicular toxicity. Methods: Randomly, thirty adult male rats were alienated into control group, SAR (4 mg\/kg) group, CYC (200 mg\/kg) group, CYC+SAR (2 mg\/kg) group and CYC+SAR (4 mg\/kg) group. SAR was orally administered at two doses (2 and 4 mg\/kg) for 7 days. CYC was injected intraperitoneally at dose (200 mg\/kg) at day 7. Results: In comparison to the CYC group, SAR at the dose of 2 and 4 mg\/kg significantly increased testis weight, testicular index, sperm count, serum testosterone and serum luteinizing hormone. Additionally, SAR at both doses induced a significant reduction in testicular MDA content in addition to increased testicular levels of GSH and TAC. Furthermore, SAR markedly upregulated testicular levels of PPAR\u03b3, Nrf2 and HO-1 in addition to decreased testicular expression of NF-\u03baB, IL-6 and TNF-\u03b1, illustrating its antioxidant and anti-inflammatory effect. SAR also significantly decreased testicular expression of caspase-3 and Bax and increased Bcl2 expression, indicating its anti-apoptotic effect. Conclusions: SAR at doses (2 and 4 mg\/kg) could ameliorate CYC-induced testicular injury in rats, possibly through antioxidant, anti-inflammatory and anti-apoptotic effect.<\/jats:p>","DOI":"10.3390\/ph19020266","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T10:02:57Z","timestamp":1770199377000},"page":"266","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Saroglitazar Mitigated Cyclophosphamide-Induced Testicular Injury: Crosstalk Between Oxidative Stress, Inflammation and Apoptosis"],"prefix":"10.3390","volume":"19","author":[{"given":"Bandar H.","family":"Alanazi","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omnia A.","family":"Nour","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7185-5378","authenticated-orcid":false,"given":"Marwa S.","family":"Serrya","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"122361","DOI":"10.1016\/j.lfs.2023.122361","article-title":"Melatonin prevents overproduction of reactive oxygen spe-cies and vascular dysfunction induced by cyclophosphamide","volume":"338","author":"Pimenta","year":"2024","journal-title":"Life Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.bpobgyn.2019.10.008","article-title":"Ovarian protection with gonadotropin-releasing hormone agonists during cyclophosphamide therapy in systemic lupus erythematosus","volume":"64","author":"Kado","year":"2020","journal-title":"Best Pract. 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