Ameliorative Effect of Vortioxetine in Experimental Model of Endocrine Pancreas Damage Related To Chronic Unpredictable Mild Stress: an Immunohistochemical Study

Abstract

Context. Chronic unpredictable mild stress (CUMS) has been widely shown to impact neurological disorders. Recently, growing evidence suggests that CUMS may also contribute to the development of metabolic conditions such as diabetes mellitus. Objective. This study aimed to investigate blood glucose levels and histopathological and immunohistochemical changes in the endocrine pancreas in an experimental rat model of CUMS, as well as the potential protective effects of vortioxetine (VOR) treatment. Subjects and methods. A total of 28 rats were divided into four groups. The CUMS group was exposed to random stressors once daily for six weeks. Rats in the VOR and CUMS+VOR groups received VOR treatment. The VOR and control groups were housed separately, without exposure to CUMS. At the end of the experiment, blood and pancreatic tissue samples were collected from all rats. Results. Blood glucose levels were elevated in the CUMS group compared to the other groups. Histopathological analysis revealed a reduction in insulin, amylin, and insulin receptor expression, along with a slight increase in glucagon expression and a small number of necrotic cells in the CUMS group. VOR treatment improved all these parameters. Conclusions. Our findings suggested that CUMS may contribute to endocrine pancreatic damage resembling diabetes mellitus, while VOR treatment may mitigate this effect