Vitamin E has a dual effect of anti-inflammatory and antioxidant activities in acetic acid–induced ulcerative colitis in rats

Vitamin E has a dual effect of anti-inflammatory and antioxidant activities in acetic acid–induced ulcerative colitis in rats

Gulgun Tahan, MD*†; Erman Aytac, MD*; Huseyin Aytekin, MD‡; Feyza Gunduz, MD†; Gulen Dogusoy, MD§; Seval Aydin, MD¶; Veysel Tahan, MD**; Hafize Uzun, MD††

From the *Department of General Surgery, Istanbul University Cerrahpasa Medical Faculty, and the †Institute of Gastroenterology, Marmara University, the Departments of ‡Internal Medicine, §Pathology and ¶Biochemistry, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey, the **Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pa., and the ††Department of Biochemistry, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey

Abstract

Background: Increased free radical production, decreased antioxidant capacity and excessive inflammation are well-known features in the pathogenesis of inflammatory bowel disease. Vitamin E is a powerful antioxidant and a scavenger of hydroxyl radicals, and it has been shown to have anti-inflammatory activities in tissues. We investigated the effects of vitamin E on inflammatory activities using an acetic acid (AA)–induced ulcerative colitis model in rats.

Methods: Wistar rats were divided into 4 groups. Acetic acid was given to 2 groups of animals to induce colitis while the other 2 groups received saline intrarectally. One AA-induced colitis group and 1 control group received vitamin E (30 U/kg/d) intraperitoneally and the pair groups received saline. After 4 days, we evaluated colonic changes biochemically by measuring proinflammatory cytokine levels in tissue homogenates and by histopathologic examination.

Results: Acetic acid caused colonic mucosal injury, whereas vitamin E administration suppressed these changes in the AA-induced colitis group (p < 0.001). Administration of AA resulted in increased levels of tumour necrosis factor-α, interleukin-1β, interleukin-6, myeloperoxidase and malondialdehyde, and decreased levels of glutathione and superoxide dismutase; vitamin E reversed these effects (all p < 0.001). Conclusion: Our study proposes that vitamin E is an effective anti-inflammatory and antioxidant and may be a promising therapeutic option for ulcerative colitis.

Résumé

Contexte : La production accrue de radicaux libres, la baisse de la capacité antioxydante et l’inflammation excessive sont des caractéristiques bien connues de la pathogenèse de la maladie entérique inflammatoire. La vitamine E est un puissant antioxydant qui récupère aussi les radicaux hydroxyles et il a été démontré qu’elle a des propriétés anti-inflammatoires dans les tissus. Nous avons étudié les effets de la vitamine E sur les activités inflammatoires au moyen d’un modèle de colite ulcéreuse provoquée par l’acide acétique (AA) chez des rats.

Méthodes : Des rats Wistar ont été divisés en 4 groupes. On a administré de l’AA à 2 groupes d’animaux pour provoquer une colite tandis que les 2 autres ont reçu une solution physiologique par voie rectale. Les sujets d’un groupe chez lesquels la colite a été provoquée par l’AA et ceux d’un groupe témoin ont reçu de la vitamine E (30 U/kg/j) par voie intrapéritoniale, et les groupes pairs ont reçu de la solution physiologique. Après 4 jours, nous avons évalué les changements biochimiques du côlon en mesurant les concentrations de cytokine pro-inflammatoire dans des homogénats de tissus et par analyse histopathologique.

Résultats : L’AA a causé des lésions de la muqueuse, tandis que l’administration de vitamine E a fait disparaître ces changements chez les sujets du groupe où la colite a été provoquée par l’AA (p < 0,001). L’administration d’AA a provoqué une élévation des concentrations du facteur α de nécrose tumorale, d’interleukine-1β, d’interleukine-6, de myéloperoxydase et de malondialdéhyde et réduit les concentrations de glutathion et de superoxyde dismutase; la vitamine E a inversé ces effets (tous p < 0,001). Conclusion : Notre étude indique que la vitamine E constitue un anti-inflammatoire et un antioxydant efficaces et peut constituer un traitement possible prometteur contre la colite ulcéreuse.


Accepted for publication Aug. 30, 2010

Competing interests: None declared.

Acknowledgement: We thank Kenneth Dorko from the University of Pittsburgh for his suggestions and critical review of the manuscript.

Contributors: Each author participated adequately in the study for substantial contributions to conception and design, acquisition of data, analysis and interpretation of data; drafting the article or revising it critically for important intellectual content; and final approval of the version to be published. All authors contributed to the scientific acquisition of data, revising the content and the final version. Beyond these critical activities, additional contributions of the authors were as follows: Dr. G. Tahan was mainly responsible for the management of the study and performed the design and statistical analysis and interpretation of data. Drs. Aytac and Aytekin organized the design and feeding of animals and performed acquisition of data and the drug administrations. Drs. G. Tahan and Aytac performed surgery and euthanized animals. Dr. Dogusoy performed histopathologic examinations of the biopsies and took pictures of the tissues. Dr. V. Tahan followed up the animals and is a contributor in writing the manuscript. Drs. Aydin and Uzun collected and stored the samples and interpreted the data regarding the disease and performed biochemical, free radical and cytokine tests. All authors approved the final version of manuscript.

DOI: 10.1503/cjs.013610

Correspondence to: Dr. G. Tahan, 5846 Hobart St., Fl. 2, Pittsburgh PA 15217 gulgunsahintahan@yahoo.com