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oai:ebyu-rdlopen.rawdatalibrary.net:ebyu/113892026-10-18T21:13:16Zopenairedrivercom_ebyu_10000col_ebyu_10001

Docosahexaenoic acid eliminates endoplasmic reticulum stress and inflammatory pathways in diabetic rat keratopathyGezer, ArzuÖzkaraca, MustafaÜstündağ, HilalSoydan, MenekşeAlkanoğlu, ÖmerBedir, GürselCorneaDiabetesDocosahexaenoic acidAnimalsAnti-Inflammatory AgentsApoptosisCorneal DiseasesCytokinesDiabetes Mellitus, ExperimentalDocosahexaenoic AcidsEndoplasmic Reticulum StressMaleRatsRats, Sprague-DawleyStreptozocincaspase 3inducible nitric oxide synthaseinterleukin 1betainterleukin 6omega 3 fatty acidtumor necrosis factorantiinflammatory agentcytokineadultangiogenesisanimal experimentanimal modelanimal tissueArticlecontrolled studyDiabetic keratopathy, characterized by corneal structural changes, is a common complication of diabetes mellitus (DM). Docosahexaenoic acid (DHA), an omega-3 fatty acid, has shown potential therapeutic benefits in various diabetic complications. This study aimed to investigate the protective effect of DHA on corneal tissue in streptozotocin (STZ)-induced type 2 DM in rats. Forty male Sprague–Dawley rats were randomly assigned to four groups (n = 10 per group): Control, DHA, DM, and DM + DHA. The DHA group received DHA by oral gavage at a dose of 100 mg/kg daily for 10 days. In the DM group, diabetes was induced by a single intraperitoneal injection of STZ at 50 mg/kg. Confirmation of diabetes induction was based on monitoring fasting blood glucose levels on the third day post-injection. The DM + DHA group underwent the same diabetes induction protocol with STZ and received DHA at 100 mg/kg daily via oral gavage for 10 consecutive days. Corneal tissue samples were collected at the end of the study period for histopathological, immunohistochemical, qRT-PCR, and ELISA analyses. Histopathological analysis showed significant edema, angiogenesis, and degeneration in the DM group compared to the control (p < 0.001). DHA treatment significantly mitigated these changes, approaching control levels (p < 0.01). Immunohistochemistry showed increased VEGFR2 and iNOS expression in the DM group, which was significantly reduced in the DM + DHA group (p < 0.01). qRT-PCR results indicated a significant decrease in Bcl-2 expression (p < 0.001) and an increase in ATF-6, IRE1, NF-κB, TNF-α, IL-1β, NLRP3, Bax, and Caspase-3 expressions in the DM group (p < 0.001). ELISA analyses revealed significantly elevated levels of inflammatory markers NF-κB, TNF-α, IL-1β, and IL-6 in the DM group compared to the control (p < 0.001). DHA treatment significantly upregulated Bcl-2 and downregulated apoptotic and inflammatory markers (p < 0.01). DHA demonstrated significant protective effects against STZ-induced corneal damage in diabetic rats by modulating apoptotic and inflammatory pathways. These findings suggest that DHA may be a promising therapeutic agent for preventing diabetic keratopathy. © 2024Elsevier B.V.2024Articlehttps://rdlopen.rawdatalibrary.net/r/ebyu/11389https://doi.org/10.1016/j.intimp.2024.1128711567-5769enInternational Immunopharmacologyinfo:eu-repo/semantics/openAccessinfo:eu-repo/semantics/articlehttps://ebyu-rdlopen.rawdatalibrary.net/tr/items/ebyu/11389