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Sulbutiamine was administered orally (60\u2009mg\/kg) to male Wistar rats for 8\u2009weeks starting 72\u2009h after a single injection of STZ (45\u2009mg\/kg, i.p.). Blood glucose level (BGL), serum testosterone level, sperm number, and motility were determined. Testicular tissue was examined histopathologically, and the Johnson score was evaluated. Levels of malondialdehyde (MDA), protein kinase C (PKC), nuclear factor erythroid\u2010derived 2\u2010like 2 (Nrf2), and proliferating cell nuclear antigen (PCNA) were measured. Apoptosis was evaluated by immunohistochemical determination of B\u2010cell lymphoma protein 2 (Bcl\u20102), Bcl\u20102 associated X\u2010protein (Bax), and caspase\u20103. Sulbutiamine administration managed to reduce BGL and boost testicular function as manifested by increased testicular weight, testosterone level, sperm number, and motility compared to the STZ group. Additionally, histopathological examination revealed an improved histological picture and Johnson score of testicular tissue after sulbutiamine treatment. Sulbutiamine administration reduced testicular PKC, MDA, and PCNA levels and increased Nrf2 compared to the untreated group. Moreover, sulbutiamine treatment suppressed apoptosis triggered by STZ as evidenced by elevated Bcl\u20102, decreased Bax and reduced caspase\u20103. The present work revealed for the first time a promising protective role of sulbutiamine against STZ\u2010induced testicular dysfunction which may add to the clinical utility of sulbutiamine. The underlying mechanisms involve reducing BGL and PKC, activating Nrf2 and inhibiting apoptosis.<\/jats:p>","DOI":"10.1002\/biof.2046","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T09:50:33Z","timestamp":1707731433000},"page":"845-862","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Ameliorating diabetes\u2010induced testicular dysfunction by modulating PKC\/Nrf2\/Bcl\u20102 signaling: Protective role of sulbutiamine"],"prefix":"10.1002","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1845-4775","authenticated-orcid":false,"given":"Maha","family":"Abdelmonem","sequence":"first","affiliation":[{"name":"Biochemistry Department, Faculty of Pharmacy Cairo University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimaa O.","family":"Ali","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Faculty of Pharmacy 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