{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T11:34:53Z","timestamp":1793100893227,"version":"4.5.0"},"reference-count":63,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Diabetic nephropathy (DN) is a leading cause of end\u2010stage renal disease, largely driven by oxidative stress and inflammation. This study evaluated the protective role of carbocisteine, a mucolytic with antioxidant and anti\u2010inflammatory properties, against streptozotocin (STZ)\u2010induced DN in rats. Male Sprague\u2013Dawley rats were divided into four groups: normal, diabetic, carbocisteine (250\u2009mg\/kg), and carbocisteine (500\u2009mg\/kg). After 8 weeks, diabetic rats showed significant hyperglycemia, weight loss, renal dysfunction (elevated serum creatinine, BUN, and urinary protein), oxidative stress (increased MDA, decreased GSH), and upregulation of inflammatory mediators; IL\u20101\u03b2, IL\u20106, and TNF\u2010\u03b1, along with downregulation of Sirt\u20101 and Nrf\u20102 expression and upregulation of NLRP3 and caspase\u20101. Moreover, diabetic rats exhibited a pro\u2010apoptotic shift, characterized by increased Bax and decreased Bcl\u20102 expression. Histopathology revealed mesangial expansion, tubular degeneration, and interstitial fibrosis. Carbocisteine treatment, particularly at the high dose, significantly improved renal function, attenuated oxidative and inflammatory responses, restored Sirt\u20101 and Nrf\u20102 levels, suppressed NLRP3\/caspase\u20101 activation, and reversed the Bax\/Bcl\u20102 imbalance, thereby ameliorating histopathological damage. These findings suggest that carbocisteine exerts nephroprotective effects in diabetic rats through modulation of the Sirt\u20101\/Nrf\u20102\/NLRP3\/caspase\u20101 signaling axis and regulation of the Bax\/Bcl\u20102 apoptotic pathway, highlighting its potential as a promising adjunct therapy for DN.<\/jats:p>","DOI":"10.1002\/ardp.70356","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T13:43:36Z","timestamp":1791812616000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Carbocisteine Confers Renoprotection in Streptozotocin\u2010Induced Diabetic Nephropathy Through Sirt\u20101\/Nrf\u20102\u2010Dependent Inhibition of NLRP3 Inflammasome Activation"],"prefix":"10.1002","volume":"359","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5142-9788","authenticated-orcid":false,"given":"Omnia A.","family":"Nour","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy Mansoura University  Mansoura Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4092-6620","authenticated-orcid":false,"given":"Mahmoud M.","family":"Samaha","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy Mansoura University  Mansoura Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,12]]},"reference":[{"issue":"2020","key":"e_1_2_11_2_1","first-page":"3","article-title":"Diabetic Nephropathy: An Overview","volume":"2067","author":"Sagoo M. 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