Please use this identifier to cite or link to this item: https://scholarhub.balamand.edu.lb/handle/uob/4252
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dc.contributor.advisorEchtay, Karimen_US
dc.contributor.authorOjaimi, Yara Alen_US
dc.date.accessioned2020-12-23T14:41:26Z-
dc.date.available2020-12-23T14:41:26Z-
dc.date.issued2019-
dc.identifier.urihttps://scholarhub.balamand.edu.lb/handle/uob/4252-
dc.descriptionIncludes bibliographical references (p. 87-98).en_US
dc.descriptionSupervised by Dr. Karim Echtay.en_US
dc.description.abstractAlthough inflammatory bowel disease (IBD) is characterized by an inflammation of the colon, studies also reported abnormalities in the non-inflamed small intestine. Energydependent nutrient absorption is decreased in the jejunum of IBD patients and animal models. The focus of our study was to investigate the bioenergetics behind this malabsorption in TNBS-induced colitis in rats. Electrode studies were used to investigate mitochondrial O2 consumption in the presence of different substrates and inhibitors of electron transport chain (ETC). Mitochondrial integrity and the specific activities of the different ETC complexes were found to be intact. However, respiratory control ratios (RCR) which reflect the mitochondrial coupling state, revealed that the mitochondria were uncoupled after 2 days of colitis induction, with RCR values in the range of 1 compared to values above 3 for sham models (p < 0.01). The coupling state of the mitochondria improved after 4 days of TNBSadministration with RCR values around 2 (p < 0.01) and was back to normal after 8 days. The uncoupling of the mitochondria was reversed by addition of GDP, a specific inhibitor of the uncoupling protein 2 (UCP2), implicating this protein in the decrease in energy metabolism. Western Blot analysis showed no change in the expression of UCP2 in the jejunum of colic rats, meaning that there was only activation of the protein which is thought to occur in response to superoxide anion. We examined the amount of ROS in jejunal epithelial cells using flow cytometry and H2DCFDA probe as a ROS detector. Epithelial ROS levels were normal after 2 days of colitis induction but displayed an insignificant but noticeable increase after 8 days. This finding supports the role of UCP2 as a sensor and negative regulator of ROS. We also found a doubling of the percentage of jejunal EpCAM+ CD45- cells (p < 0.05) at 2 days after TNBS-administration which can also affect absorption and help protect against epithelial damage. In conclusion, ROS production in the jejunum activates UCP2 which has an antioxidant activity. Uncoupling of the mitochondria decreases the efficiency of energy production, leading to a decrease in energy-dependent nutrient absorption. Our study is the first to pinpoint the involvement of energy production, and mainly UCP2, in the small intestinal abnormalities observed in colitis. Targeting mitochondrial bioenergetics might improve nutrient absorption and decrease the severity of UC and its complications.en_US
dc.description.statementofresponsibilityYara Al Ojaimien_US
dc.format.extentxiii, 98 p. :ill., tables ;30 cmen_US
dc.language.isoengen_US
dc.rightsThis object is protected by copyright, and is made available here for research and educational purposes. Permission to reuse, publish, or reproduce the object beyond the personal and educational use exceptions must be obtained from the copyright holderen_US
dc.subject.lcshInflammatory bowel diseasesen_US
dc.subject.lcshMitochondriaen_US
dc.titleEnergy dependent nutrient uptake in TNBS-induced colitis : a possible role of mitochondrial efficiency in ATP production and uncoupling-2 activityen_US
dc.typeThesisen_US
dc.contributor.facultyFaculty of Medicine and Medical Sciencesen_US
dc.contributor.institutionUniversity of Balamanden_US
dc.date.catalogued2019-05-02-
dc.description.degreeMS in Biomedical Sciencesen_US
dc.description.statusPublisheden_US
dc.identifier.ezproxyURLhttp://ezsecureaccess.balamand.edu.lb/login?url=http://olib.balamand.edu.lb/projects_and_theses/Th-BmS-22.pdfen_US
dc.identifier.OlibID191556-
dc.provenance.recordsourceOliben_US
Appears in Collections:UOB Theses and Projects
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