Investigation of the effects of experimental rat colitis model on histopathological and oxidative changes in colon tissue, and fecal microbiota: The therapeutic value of alpha lipoic acid


Thesis Type: Postgraduate

Institution Of The Thesis: Gazi University, Sağlık Bilimleri Enstitüsü, Turkey

Approval Date: 2024

Thesis Language: Turkish

Student: İrem TANER

Supervisor: Mürşide Ayşe Demirel

Open Archive Collection: AVESIS Open Access Collection

Abstract:

Ulcerative colitis is a chronic inflammation of the gastrointestinal system. In addition to treatments aimed at healing inflammation and tissue damage, addressing the imbalance in the intestinal microbiota is crucial. The aim of the thesis is to investigate the effects of alpha lipoic acid, either alone or in combination with mesalamine, on antioxidant activity, anti inflammatory responses, proptosis, and gut microbiota in a rat model of ulcerative colitis. In our study, rats were divided into control, colitis, mesalamine, alpha-lipoic acid, and mesalamine+alpha-lipoic acid groups. The control group did not undergo colitis induction, while colitis was induced in other groups by intrarectal administration of acetic acid. The disease activity index was the highest in the colitis group and the lowest in the mesalamine+alpha-lipoic acid group among the treatment groups. Macroscopic scores in the colitis, mesalamine, and alpha-lipoic acid groups were significantly elevated compared to the control group. The OSI was the highest in the colitis group, with significantly elevated levels compared to the control, alpha-lipoic acid, and mesalamine+alpha-lipoic acid groups. The nitrotyrosine level was also highest in the colitis group, and significantly elevated compared to the control, mesalamine, alpha-lipoic acid, and mesalamine+alpha-lipoic acid groups. NLRP3 inflammasome and GSDMD levels showed significant increases in the colitis group compared to the control group, while GSDMD protein levels were significantly reduced in the mesalamine+alpha-lipoic acid group compared to the colitis group. Histopathological scoring in the colitis group increased, while tight junction proteins decreased; alpha-lipoic acid administration significantly ameliorated these parameters. It was determined that colitis caused intestinal dysbiosis and that alpha-lipoic acid contributed to the regulation of microbiota. Our results indicate that alpha-lipoic acid has beneficial effects on increased inflammation, oxidative stress, inflammasome parameters, and microscopic scores, as well as on the reduction of tight junction proteins and dysbiosis of the intestinal microbiota associated with colitis.

Key Words : Alpha lipoic acid, colitis, microbiota, oxidation, rat