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Oxidative stress\u00a0is increased in diabetes (DM) due to AGEs formation and the utilization of NADPH by aldo\u2010keto reductase, AKR1B1(AR), the first enzyme in polyol pathway. Since inhibition of AR is an attractive approach for the management of diabetic eye diseases, we aimed to compare the effects of a novel AR inhibitor (ARI)\/antioxidant (AO) compound cemtirestat on eye tissues with the effects of ARI drug epalrestat and AO\u00a0agent stobadine in rat model for glycotoxicity. One group of rats was fed high fructose (10% drinking water; 14 weeks), while type\u20102 DM was induced in the other group of rats with fructose plus streptozotocin (40\u2009mg\/kg\u2010bw\/day). Diabetic (D) and nondiabetic fructose\u2010fed rats (F) were either untreated or treated with two different doses of cemtirestat (2.5 and 7.5\u2009mg\/kg\u2010bw\/day), epalrestat (25 and 50\u2009mg\/kg\u2010bw\/day),\u00a0or stobadine (25 and 50\u2009mg\/kg\u2010bw\/day) for 14 weeks. Cemtirestat, epalrestat, and stobadine elaviate the increase in TNF\u2010\u03b1, IL\u20101\u03b2, NF\u2010\u0199B, and caspase\u20103 in retina, lens, cornea, and sclera of F and D rats. Both glycotoxicity models resulted in a decrease in GSH to GSSG ratio and a change in glutathione S\u2010transferase activity in eye tissues, but these alterations were improved especially with cemtirestat and stobadine. Lens <jats:sc>D<\/jats:sc>\u2010sorbitol of D rats increased more than that of F rats, this increase was only attenuated by cemtirestat and epalrestat. Epalrestat was more effective than cemtirestat and stobadine in inhibiting the increase of vascular endothelial growth factor (VEGF)\u00a0in the retina of F and D rats. Cemtirestat and stobadine but not epalrestat decreased high level of N\u03b5\u2010(carboxymethyl)lysine in the lens and retina of F and D rats. Cemtirestat is a potential therapeutic in protecting the rat eye against glycotoxicity insults.<\/jats:p>","DOI":"10.1002\/cbf.3818","type":"journal-article","created":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T14:53:53Z","timestamp":1686149633000},"page":"622-632","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Cemtirestat, an aldose reductase inhibitor and antioxidant compound, induces ocular defense against oxidative and inflammatory stress in rat models for glycotoxicity"],"prefix":"10.1002","volume":"41","author":[{"given":"Tala","family":"Reihanifar","sequence":"first","affiliation":[{"name":"Cellular Stress Response and Signal Transduction Research Laboratory, Department of Medical Pharmacology, Faculty of Medicine Gazi University Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muzaffer","family":"\u015eahin","sequence":"additional","affiliation":[{"name":"Department 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