en Medical Genetics Medical Genetics Original Research Original Research <span style="font-size:13pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="text-autospace:none"><span new="" roman="" style="font-family:" times=""><span style="font-style:italic"><b><span style="font-size:9.0pt"><span style="font-style:normal">Background: </span></span></b><span style="font-size:9.0pt"><span style="font-style:normal">The role of histamine H3 receptors (H3Rs) in gastric protection and anti-inflammatory function is controversial. In this study, we investigated the gastroprotective effect of a histamine H3 receptor antagonist drug, betahistine, on cytokine-induced neutrophil chemoattractant (CINC) gene expression in a rat model of indomethacin-induced gastric mucosal injury. </span></span></span></span></span></span></span></span><br> <span style="font-size:13pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="text-autospace:none"><span new="" roman="" style="font-family:" times=""><span style="font-style:italic"><b><span style="font-size:9.0pt"><span style="font-style:normal">&nbsp;&nbsp; Methods:</span></span></b><span style="font-size:9.0pt"><span style="font-style:normal"> In this experiment, rats were divided into four groups; the control group received no treatment, group 2 was treated with indomethacin at a dose of 25 mg/kg, group 3 pre-treated with famotidine at a dose of 50 mg/kg, and group 4 pre-treated with betahistine (as a reference drug) at a dose of 50 mg/kg. The last two groups were followed by indomethacin administration (25 mg/kg), three days later. The obtained values were expressed as the mean and standard error of the mean (mean &plusmn; SEM). The level of statistical significance was set at &alpha; = 0.05</span></span></span></span></span></span></span></span><br> <span style="font-size:13pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="text-autospace:none"><span new="" roman="" style="font-family:" times=""><span style="font-style:italic"><span style="font-size:9.0pt"><span style="font-style:normal">&nbsp;&nbsp; <b>Results:</b> Indomethacin treatment resulted in large ulcerative lesions with a mean ulcer index of 29&plusmn; 13.63 mm. However, ulcerative indices were significantly improved in groups pre-treated with famotidine (15.5 &plusmn; 8.68 mm; </span></span><span style="font-size:9.0pt">P</span><span style="font-size:9.0pt"><span style="font-style:normal"> < 0.05) and betahistine (11&plusmn;5.66 mm, </span></span><span style="font-size:9.0pt">P </span><span style="font-size:9.0pt"><span style="font-style:normal">< 0.01), compared to the indomethacin-treated group. The expression levels of gastric CINC-2ɑ were significantly elevated in indomethacin-induced groups by 0.028&plusmn;0.05 in the indomethacin group, 0.005&plusmn;0.01 in indomethacin + famotidine, and 0.012&plusmn;0.03 in indomethacin + betahistine groups, compared to the control group (</span></span><span style="font-size:9.0pt">P</span><span style="font-size:9.0pt"><span style="font-style:normal"> < 0.05). Besides, pre-treatment with betahistine significantly reduced the expression of CINC-2ɑ induced by indomethacin administration (</span></span><span style="font-size:9.0pt">P</span><span style="font-size:9.0pt"><span style="font-style:normal"> < 0.05). </span></span></span></span></span></span></span></span><br> <span style="font-size:13pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="text-autospace:none"><span new="" roman="" style="font-family:" times=""><span style="font-style:italic"><span style="font-size:9.0pt"><span style="font-style:normal">&nbsp;&nbsp; <b>Conclusion:</b> Betahistine for five days before administrating indomethacin reduced the ulcer index and downregulated the expression of CINC-2&alpha; significantly. Overall, pre-treatment with betahistine protects against the gastric damage induced by indomethacin by lowering the expression of CINC-2ɑ.</span></span></span></span></span></span></span></span><br> &nbsp; : Betahistine, H3 receptor antagonist, Cytokine-induced neutrophil chemoattractant, Non-steroidal anti-inflammatory drugs, Gastric ulcer 704 709 http://mjiri.iums.ac.ir/browse.php?a_code=A-10-8668-1&slc_lang=en&sid=1 Shaghayegh Tarani shaghayeghtarani@yahoo.com 200319475328460089523 0009-0008-5964-785X No Student Research Committee, Alborz University of Medical Sciences, Karaj, Iran Gelareh Vahabzadeh gelareh.vahabzadeh@gmail.com 200319475328460089524 200319475328460089524 No Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran Hasan Fallah Huseini huseini_fallah@yahoo.com 200319475328460089525 200319475328460089525 No Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran Armin Khavandegar arminkhavandegar@yahoo.com 200319475328460089526 200319475328460089526 No Sina Trauma and Surgery Research Center, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran Bahareh Tavakoli-far tavakkolifarb@yahoo.com 200319475328460089527 200319475328460089527 No Dietary Supplements and Probiotic Research Center, Alborz University of Medical Sciences, Karaj, Iran Roshanak Jazayeri roshanakjazayeri@gmail.com 200319475328460089528 200319475328460089528 Yes Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran