International Medical Journal Vol. 20, No. 1, pp. 29 - 33 , February 2013 INTERNAL MEDICINE Effect of Zinc on Chronic Stress Induced Small Intestinal Changes in Rats Jesmine Khan 1) , Wan Salman Wan Saudi 2) , Mohammed Nasimul Islam 1) ABSTRACT Introduction: Zinc is essential for the development of enterocytes. Healthy enterocytes help to maintain efficient intestinal barrier to prevent excessive intestinal permeabilty to harmful agents. Chronic stress compromises morphology and permeability of the small intestine of rats. Objectives: To observe whether zinc supplementation can attenuate chronic stress induced small intestinal morphology and permeability changes in rats. Materials and methods: Forty male Sprague Dawley rats were divided into control (C), control with zinc CZ), stress (S) and stress with zinc (SZ) groups with ten rats in each group. Water avoidance stress was applied one hour daily for 10 consecutive days. Body weight gain, food and water intake and number of stool pellet after every stress session was measured. On the 11th day, fluorescent Isothiocyanate Dextran (FITC) was injected into the surgically created small intestinal loops. Blood was collect- ed one hour after the injection to measure serum FITC dextran. Jejunum and ileum was collected to measure morphological parameters. One way ANOVA was done to analyze data. Results: S group had significantly shorter crypt depth in ileum, shorter villus height in jejunum, fewer goblet cells in crypts of ileum and jejunum and fewer goblet cells in villus of jejunum as compared to the C group. SZ group had significantly longer crypt depth, longer villus height and higher number of goblet cells in crypts and villus of ileum and jejunum as compared to the S group. S group had significantly higher permeability to FITC and increased inflammatory cell infiltration in ileum and jejunum as compared to the C group. SZ group had significantly lower permeability to FITC and fewer inflammatory cells infil- tration in ileum and jejunum as compared to the S group. Conclusion: Chronic stress compromised the small intestinal morphology and permeability which were attenuated by zinc supplementation. KEY WORDS chronic stress, small intestine, zinc Received on December 26, 2011 and accepted on March 12, 2012 1) Faculty of Medicine, Universiti Teknologi Mara (UiTM) Malaysia 2) School of Medicine, Universiti Malaysia Sabah, Malaysia Correspondence to: Jesmine Khan (e-mail: jesminek@yahoo.com) 29 INTRODUCTION Beside its main function of digestion and absorption, small intestinal mucosa acts as an important barrier to toxic and harmful materials and protects human being from different antigenic and inflammatory reactions. Several researches have reported the effect of chronic psycholog- ical stress on small intestinal structure and function. Chronic psycho- logical stress has been reported to cause altered jejunal and ileal mor- phology, increased permeability, increased ion secretion, binding of luminal bacteria to surface epithelium, increased uptake of luminal antigens through follicle associated epithelium of Peyer's patches, sensitization of the intestinal mucosa and initiation of mucosal inflammation by luminal antigens (Saudi WSW, Islam MN, Khan J 2009; Collins S M 2001; Soderholm JD, Perdue MH 2001; Soderholm JD, Yang PC, Ceponis P 2002; Velin AK, Ericson AC, Braaf Y 2004). Stress is an important cause for the development as well as exag- geration of intestinal inflammation in inflammatory bowel diseases (IBD) (Collins S M 2001; Mayer E A 2000). Compromised intestinal barrier function may be an initiating or propagating factor in intestinal diseases. All such changes might hamper the role of gastro intestinal tract in immune protection of the body. Zinc, a trace element present in all body tissues and fluids, is essential for the survival and function of cells. Zinc is involved in cell growth as a regulator of protein synthesis and in cell replication through the formation of "zinc fingers," structural components of DNA-binding proteins (Berdanier CD.1998). Zinc may contribute to the host defense by maintaining the structure and function of the membrane barrier and this is particularly important in the intestine, which is continuously exposed to a variety of pathogens and noxious agents. MATERIALS AND METHODS Forty, six-week old male Sprague Dawley rats with a mean body weight of 149.69 ±3.92 g were used in this study. They were kept in metabolic cages in the animal room under standard laboratory condi- tions, at 12 hours light-dark cycle and exchange of room air 24 hours per day. Rats had free access to rat chow and deionized water. All the procedures described in the study were approved by the animal ethi- cal committee of the institution. Rats were randomly divided into four groups: control (C; n = 10), control with zinc supplement (CZ; n = 10), stress (S; n = 10) and stress with zinc supplement (SZ; n = 10) groups. Zinc was provided in a dose of 10 mg zinc sulphate (Sigma-Aldrich, Germany) dis- C 2013 Japan International Cultural Exchange Foundation & Japan Health Sciences University