α-ketoglutarate Ameliorates Colitis Through Modulation of Inflammation, ER Stress, and Apoptosis

Overview

Journal Toxicol Rep

Date 2025 Jan 31

PMID 39886045

Authors

Ankita Mandal

Sharmistha Banerjee

Sumit Ghosh

Sima Biswas

Angshuman Bagchi

Parames C Sil

Affiliations

Soon will be listed here.

Abstract

Colitis is an inflammatory disorder of the gastrointestinal tract. A widely consumed dietary nutrient, α-ketoglutarate (α-KG) is known to play a crucial role in cellular metabolism and provide protection to intestinal epithelium under various pathophysiological conditions. In this study, 2,4,6-trinitrobenzenesulfonic acid (TNBS) was used to induce colitis in Wistar rats. After 36 hours of TNBS administration, the rats were orally treated with a solution of α-KG at 1 g/kg body weight for 5 days. Development of colitis was confirmed by observable physical symptoms of repeated loose blood-mixed stool, apathy for food and weight loss. Macroscopic inspection revealed an inflamed colonic surface with ulcerations. Histopathological observations included alterations in crypts-structure and disruption in both epithelial and mucosal layers of colon in colitis induced rats. Colitis resulted in elevated levels of pro-inflammatory cytokines, ER stress-mediated cell death and intrinsic apoptosis pathway. The ameliorative effects of α-KG against TNBS-mediated toxicity were confirmed through molecular technics and docking analysis. Additionally, there were no instances of toxicity of α-KG. Therefore, α-KG can be considered as a valuable therapeutic agent for further comprehensive research.

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