Glutamine Prevents Fibrosis Development in Rats with Colitis Induced by 2,4,6-Trinitrobenzene Sulfonic Acid

Abstract

We investigated the effects of glutamine on the development of colonic fibrosis and on the expression of the major fibrogenic factors in a rat model of experimental colitis. Colitis was induced in one-half of the male Wistar rats by intracolonic administration of 30 mg of 2,4,6-trinitrobenzene sulfonic acid (TNBS). L-Glutamine (25 mg/kg) was administered rectally to one-half of the controls and one-half of the colitic rats. The control, control+glutamine, TNBS, and TNBS+glutamine groups were studied at d 2 and 7 after colitis induction. Glutamine induced a significant decrease in the area of colon fibrosis and in the staining of α-smooth muscle actin positive cells within areas of extracellular matrix deposits in the submucosa. Collagen synthesis was stimulated following TNBS administration, with a significant increase in procollagen IV, collagen III, and collagen Iα2 mRNA levels in the colon by d 2 after TNBS instillation. Tissue inhibitor of metalloproteinase, connective tissue growth factor, transforming growth factor-β, platelet-derived growth factor, and phosphorylated Smad3 were overexpressed in the colon of TNBS-treated rats. These effects were significantly abrogated in the colitic rats treated with glutamine. Our findings suggest that glutamine treatment not only attenuates the outcome of TNBS-induced colitis by reducing the inflammatory response but also by downregulating the increased expression of several gene pathways that contribute to the accumulation of matrix proteins. This molecule may be an interesting candidate for reducing the risk of fibrosis and stricture formation in inflammatory bowel disease.