New Insights on the potential therapeutic effects of glibenclamide and Obeticholic acid against Alloxan-Induced diabetes mellitus in rat model.

Int Immunopharmacol

Department of Pathology and Clinical Pathology, Faculty of Veterinary Medicine, Alexandria University, Egypt. Electronic address:

Published: December 2024

AI Article Synopsis

  • Diabetes mellitus is a widespread metabolic disorder, and this study investigates the effects of glibenclamide (Gli) and obeticholic acid (OCA) on alloxan-induced diabetes in male rats.
  • The treatments over 30 days showed that Gli lowered blood sugar and improved insulin levels, while OCA also improved blood sugar but did not affect insulin levels as much.
  • Both drugs reduced oxidative stress, liver function disturbances, and improved liver and pancreatic tissue health, indicating their potential for managing diabetes-related complications.

Article Abstract

Diabetes mellitus (DM) represents a highly prevalent metabolic disorder across the globe. This study aimed to determine the ameliorative efficacy of glibenclamide (Gli) and obeticholic acid (OCA) against biochemical and pathological changes related to alloxan-induced diabetes. Twenty male Wistar rats were allocated into four groups; Control group, Diabetic group: received intraperitoneal injection of alloxan (120 mg/kg) for induction of diabetes, Diabetic + Gli group: Diabetic rats treated daily with oral Gli (5 mg/kg) and Diabetic + OCA group: Diabetic rats treated daily with oral OCA (10 mg/kg). All rats were subjected to 30 days treatments. Our results indicated that Gli successfully ameliorated hyperglycemia and dyslipidemia with a significant decline in serum pancreatic lipase activity and increased insulin level, while OCA had the same effect but without any enhancement in serum insulin levels. Additionally, the disturbances in liver function-related parameters and the evoked oxidative stress, interleukin(IL)-6 and IL-10 in the liver and pancreas were abrogated upon treatment with Gli and OCA. Furthermore, Gli and OCA increased AMP-activated protein kinase (P-AMPK), insulin receptor substrate 1 (IRS1), farnesoid X receptor (FXR), and glucagon-like peptide-1 receptor (GLP-1R) expressions and downregulated sterol regulatory element binding protein-1c mRNA expression. Besides, Gli and OCA have alleviated diabetes-induced histopathological distortions in hepatic and pancreatic tissues and enhanced the immunoexpression of insulin, and proliferating cell nuclear antigen with decreased immune reactivity of glucagon within pancreatic tissues. Gli and OCA decreased the immune reactivity of nuclear factor kappa B and increased the glycogen content of hepatic tissues. In conclusion, OCA is efficacious in the management of dyslipidemia and hyperglycemia of DM and its related oxidative stress.

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Source
http://dx.doi.org/10.1016/j.intimp.2024.113469DOI Listing

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