Inflammatory bowel disease (IBD) is a term used to describe disorders that involve chronic inflammation of the digestive tract, such as Crohn’s Disease and Ulcerative Colitis. IBD currently affects three million people in the United States, with many going undiagnosed. A few Ulcerative Colitis patient studies have shown alterations in mitochondrial function. Our study aims to identify the role of mitochondrial dysfunction in a chemically induced rat model of Crohn’s Disease. Rats received two injections of indomethacin (7.5 mg/kg) 24 hours apart. The peak of the disease is reported to be between day 2 and 3 post-injection with a duration of 7 days with the possibility of a cycling effect. Therefore, colon tissue was collected on day 2, day 3, day 7, and day 30 post-injection for histology and mitochondria function assays. Our animals showed a significant decrease in body weight at day 2 and 3 post-injection with the females having a more significant decrease. On day 2, the intact mitochondrial respiration was significantly decreased in both males and females. However, citrate synthase activity was not significantly increased suggesting that this increase is possibly due to the respiratory burst from increased inflammatory cells. Indeed, on day 2, there is significant histological evidence of inflammatory cell invasion. On day 3, the females showed a significant decrease in mitochondrial respiration while the males did not. The ROS production on day 2 was significantly increased in both males and females with the females remaining increased on day 3. Examination of the individual electron transport complexes of mitochondrial oxidative phosphorylation showed a significant decrease in the activities of complex I, II, and IV at the peak of the disease. Day 7 and Day 30 do not show any significant differences currently. Overall, colon mitochondrial function is altered in the indomethacin-induced rat model of Crohn’s Disease during the peak of the disease suggesting that mitochondria play a role in the development of the disease. Further studies will be performed, and additional animal models will be tested to confirm these findings. This study will provide a better understanding of the role mitochondria play in the development of IBD and provide an avenue for the development of strategies for reestablishing normal mitochondrial function that could provide options for preventive and therapeutic interventions for IBD where there are limited treatment options.

Sex differences in mitochondrial dysfunction following the induction of Crohn’s disease in rats

ACS Fall 2021

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