Efficacy of Oral Nanoparticle-Encapsulated Insulin in Reducing Oxidative Stress and Enhancing Tissue Integrity in a Diabetic Rat Model

Nawel Kaddour,1 Farah Benyettou,2 Kawtar Moulai,1 Abdelouahab Mebarki,1 Rose Ghemrawi,3,4 Zine-Charaf Amir,5 Hafida Merzouk,1 Ali Trabolsi,2 Nassima Amel Mokhtari-Soulimane1 1Laboratory of Physiology, Physiopathology, and Biochemistry of Nutrition, Department of Biology, Faculty of Sciences of Nature and Life, Earth Sciences and Universe (SNVSTU), University of Tlemcen, Tlemcen, 13000, Algeria; 2Chemistry Program, New York University Abu Dhabi (NYUAD), Abu Dhabi, 129188, United Arab Emirates; 3College of Pharmacy, Al Ain University, Abu Dhabi, P.O. Box 112612, United Arab Emirates; 4AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi, P.O. Box 112612, United Arab Emirates; 5Department of Anatomy and Pathological Cytology, University Hospital Center Mustapha Pacha, Algiers, AlgeriaCorrespondence: Nassima Amel Mokhtari-Soulimane, Faculty SNVSTU University of Tlemcen, BP 119, Rocade 2 Mansourah, Tlemcen, 13000, Algeria, Tel +213 557 229 623, Email [email protected]; [email protected] Ali Trabolsi, Chemistry Program, New York University Abu Dhabi (NYUAD), Abu Dhabi, 129188, United Arab Emirates, Tel +971 26284575, Email [email protected]: Diabetes mellitus, a chronic metabolic disorder, leads to systemic organ damage characterized by oxidative stress and structural alterations, contributing to increased morbidity and mortality. Traditional subcutaneous insulin therapy, while managing hyperglycemia, often falls short in addressing the oxidative damage and preventing organ-specific complications. This study evaluates the therapeutic efficacy of a novel oral nanoparticle-mediated insulin (nCOF/Insulin) against these diabetes-induced changes, comparing it with traditional subcutaneous insulin in a streptozotocin (STZ)-induced diabetic rat model.Methods: We induced diabetes in Wistar rats, dividing them into four groups: standard control, diabetic control, diabetic treated with subcutaneous insulin, and diabetic treated with oral nanoparticle-mediated insulin (nCOF/Insulin). Assessments included organ and body weights, histopathological examinations, and oxidative stress markers (MDA and PCOs) across various organs, including the brain, muscle, intestine, spleen, heart, liver, kidney, and adrenal glands. Additionally, we evaluated antioxidant parameters (GSH and catalase) and conducted immunohistochemical analysis of E-cadherin to assess intestinal integrity.Results: Our findings reveal that STZ-induced diabetes significantly impacts organ health, with subcutaneous insulin providing limited mitigation and, in some cases, exacerbating oxidative stress. Conversely, oral nCOF/Insulin treatment effectively restored organ and body weights, reduced oxidative stress markers, and mitigated histological damage. This suggests that oral nCOF/Insulin not only offers superior glycemic control but also addresses the underlying oxidative stress.Conclusion: nCOF/Insulin emerges as a promising treatment for diabetes, with the potential to improve patient quality of life by ameliorating oxidative stress and preventing organ-specific complications. This study underscores the need for further investigation into the long-term effects and mechanisms of action of oral nCOF/Insulin, aiming to revolutionize diabetes management and treatment strategies.Keywords: oral nanoparticle-mediated insulin, diabetes mellitus, oxidative stress, organ toxicity, diabetic complications