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            <front>

                <journal-meta>
                                                                <journal-id>j res pharm</journal-id>
            <journal-title-group>
                                                                                    <journal-title>Marmara Pharmaceutical Journal</journal-title>
            </journal-title-group>
                            <issn pub-type="ppub">1309-0801</issn>
                                                                                                        <publisher>
                    <publisher-name>Marmara University</publisher-name>
                </publisher>
                    </journal-meta>
                <article-meta>
                                        <article-id/>
                                                                                                                                                                                            <title-group>
                                                                                                                        <article-title>The effect of betulinic acid on TNBS-induced experimental colitis</article-title>
                                                                                                                                                                                                <trans-title-group xml:lang="tr">
                                    <trans-title>The effect of betulinic acid on  TNBS-induced experimental colitis</trans-title>
                                </trans-title-group>
                                                                                                    </title-group>
            
                                                    <contrib-group content-type="authors">
                                                                        <contrib contrib-type="author">
                                                                <name>
                                    <surname>Şener</surname>
                                    <given-names>Tarık</given-names>
                                </name>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                <name>
                                    <surname>Kardaş</surname>
                                    <given-names>Rıza</given-names>
                                </name>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                <name>
                                    <surname>Şehirli</surname>
                                    <given-names>Ahmet</given-names>
                                </name>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                <name>
                                    <surname>Ekşioğlu-demiral</surname>
                                    <given-names>Emel</given-names>
                                </name>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                <name>
                                    <surname>Yüksel</surname>
                                    <given-names>Meral</given-names>
                                </name>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                <name>
                                    <surname>Çetinel</surname>
                                    <given-names>Şule</given-names>
                                </name>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                <name>
                                    <surname>Yeğen</surname>
                                    <given-names>Berrak</given-names>
                                </name>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                <name>
                                    <surname>Şener</surname>
                                    <given-names>Göksel</given-names>
                                </name>
                                                            </contrib>
                                                                                </contrib-group>
                        
                                        <pub-date pub-type="pub" iso-8601-date="20140307">
                    <day>03</day>
                    <month>07</month>
                    <year>2014</year>
                </pub-date>
                                        <volume>17</volume>
                                        <issue>1</issue>
                                        <fpage>52</fpage>
                                        <lpage>59</lpage>
                        
                        <history>
                                    <date date-type="received" iso-8601-date="20140307">
                        <day>03</day>
                        <month>07</month>
                        <year>2014</year>
                    </date>
                                            </history>
                                        <permissions>
                    <copyright-statement>Copyright © 1985, Marmara Pharmaceutical Journal</copyright-statement>
                    <copyright-year>1985</copyright-year>
                    <copyright-holder>Marmara Pharmaceutical Journal</copyright-holder>
                </permissions>
            
                                                                                                <abstract><p>ABSTRACT: In this study we have investigated the possible protective effect of betulinic acid(BA) on colonic inflammation in rats. Colitis was induced in Sprague-Dawley rats of bothsexes by intracolonic administration of 1 ml trinitrobenzene sulphonic acid (TNBS). Colitisinducedrats received orogastrically either betulinic acid (50 mg/kg/day) or vehicle (0.05%DMSO) for 3 days. At the 72nd hour of colitis induction, the rats were decapitated and trunkblood was collected for the measurement of TNF-, IL-1, lactate dehydrogenase (LDH) levelsand total antioxidant capacity (AOC). The distal 8 cm of colon were scored macroscopically,and the degree of oxidant damage was evaluated by malondialdehyde (MDA) andglutathione (GSH) levels, myeloperoxidase activity (MPO), collagen content and by histologicalanalysis. Generation of oxidants was evaluated by tissue luminol and lucigeninchemiluminescences (CL). Colitis caused significant increases in the colonic CL values,macroscopic damage scores, MDA, MPO and collagen levels, along with a significant decreasein tissue GSH level. Similarly, serum TNF-, IL-1, as well as LDH were elevated andAOC was reduced in the vehicle-treated colitis group as compared to control group. On theother hand, betulinic acid treatment reversed all these biochemical indices, as well as histopathologicalalterations induced by TNBS, suggesting that betulinic acid protects the colonictissue via its radical scavenging and antioxidant activities.KEY WORDS: betulinic acid; colitis; oxidative damage; inflammation;trinitrobenzene sulphonic acid</p></abstract>
                                                                                    
            
                                                            <kwd-group>
                                                    <kwd>betulinic acid; colitis; oxidative damage; inflammation; trinitrobenzene sulphonic acid</kwd>
                                            </kwd-group>
                                                        
                                                                                                                                                    </article-meta>
    </front>
    <back>
                            <ref-list>
                                    <ref id="ref1">
                        <label>1</label>
                        <mixed-citation publication-type="journal">Shanahan F. Pathogenesis of ulcerative colitis. Lancet 1993;342:407–11.</mixed-citation>
                    </ref>
                                    <ref id="ref2">
                        <label>2</label>
                        <mixed-citation publication-type="journal">Keshavarzian A, Sedghi S, Kanofsky J, List T, Robinson C, Ibrahim C, Winship D. Excessive production of reactive oxygen metabolites by inflamed colon: analysis by chemiluminescence probe. Gastroenterology 1992;103: 177-85.</mixed-citation>
                    </ref>
                                    <ref id="ref3">
                        <label>3</label>
                        <mixed-citation publication-type="journal">Podolsky DK. Inflammatory bowel disease. N Engl J Med 2002;347:417-29.</mixed-citation>
                    </ref>
                                    <ref id="ref4">
                        <label>4</label>
                        <mixed-citation publication-type="journal">Ghosh P, Mandal A, Chakraborty P, Rasul MG, Chakraborty M, Saha A. Triterpenoids from Psidium guajava with Biocidal Activity. Indian J Pharm Sci 2010;72:504-7.</mixed-citation>
                    </ref>
                                    <ref id="ref5">
                        <label>5</label>
                        <mixed-citation publication-type="journal">Isik F, Tunali Akbay T, Yarat A, Genc Z, Pisiriciler R, Caliskan-Ak E, Cetinel S, Altıntas A, Sener G. Protective Effects of Black Cumin (Nigella sativa) Oil on TNBS-Induced Experimental Colitis in Rats. Dig Dis Sci 2011;256:721-30.</mixed-citation>
                    </ref>
                                    <ref id="ref6">
                        <label>6</label>
                        <mixed-citation publication-type="journal">Genc Z, Yarat A, Tunali-Akbay T, Sener G, Cetinel S, Pisiriciler R, Caliskan-Ak E, Altıntas A, Demirci B. The Effect of Stinging Nettle (Urtica dioica) Seed Oil on Experimental Colitis in Rats. J Med Food 2011; 14:1554-61.</mixed-citation>
                    </ref>
                                    <ref id="ref7">
                        <label>7</label>
                        <mixed-citation publication-type="journal">Sami A, Taru MK, Salme K, Jari YK. Pharmacological properties of the ubiquitous natural product betulin. Eur J Pharm Sci 2006;29:1-13.</mixed-citation>
                    </ref>
                                    <ref id="ref8">
                        <label>8</label>
                        <mixed-citation publication-type="journal">Aiken C, Chen CH. Betulinic acid derivatives as HIV-1 antivirals. Trends Mol Med 2005;11: 31-6.</mixed-citation>
                    </ref>
                                    <ref id="ref9">
                        <label>9</label>
                        <mixed-citation publication-type="journal">Ekşioğlu-Demiralp E, Kardaş ER, Ozgül S, Yağcı T, Bilgin H, Sehirli O, Ercan F, Sener G. Betulinic acid protects against ischemia/reperfusion-induced renal damage and inhibits leukocyte apoptosis. Phytother Res 2010; 24:325-32.</mixed-citation>
                    </ref>
                                    <ref id="ref10">
                        <label>10</label>
                        <mixed-citation publication-type="journal">Wallace JL, Braquet P, Ibbotson GC, MacNaugton WK, Cirino G. Assessment of the role of platelet activating factor in an animal model of inflammatory bowel disease. J Lipid Med 1989;1: 13-23.</mixed-citation>
                    </ref>
                                    <ref id="ref11">
                        <label>11</label>
                        <mixed-citation publication-type="journal">Martinek RG. A rapid ultraviolent spectrophotomeetric lactic dehydrogenase assay. Clin Chem Acta 1972;40:91-9.</mixed-citation>
                    </ref>
                                    <ref id="ref12">
                        <label>12</label>
                        <mixed-citation publication-type="journal">Haklar G, Ulukaya-Durakbaşa C, Yüksel M, Daglı T, Yalcin AS. Oxygen radicals and nitric oxide in rat mesenteric ischemia-reperfusion: modulation by L-arginine and N-nitro-L-arginine methyl ester. Clin Exp Pharmacol Physiol 1998;25: 908-12.</mixed-citation>
                    </ref>
                                    <ref id="ref13">
                        <label>13</label>
                        <mixed-citation publication-type="journal">Beuge JA, Aust SD. Microsomal lipid peroxidation. Meth Enzymol 1978;52:302-11.</mixed-citation>
                    </ref>
                                    <ref id="ref14">
                        <label>14</label>
                        <mixed-citation publication-type="journal">Beutler E. Glutathione in red blood cell metabolism. A Manuel of Biochemical Methods, Grune&amp;Stratton, New York 1975,112-114.</mixed-citation>
                    </ref>
                                    <ref id="ref15">
                        <label>15</label>
                        <mixed-citation publication-type="journal">Hillegass LM, Griswold DE, Brickson B, AlbrightsonWinslow C. Assessment of myeloperoxidase activity in whole rat kidney. J Pharmacol Meth 1990; 24:285-295.</mixed-citation>
                    </ref>
                                    <ref id="ref16">
                        <label>16</label>
                        <mixed-citation publication-type="journal">Bradley PP, Priebat DA, Christersen RD, Rothstein G. Measurement of cutaneous inflammation. Estimation of neutrophil content with an enzyme marker. J Invest Dermatol 1982;78:206–9.</mixed-citation>
                    </ref>
                                    <ref id="ref17">
                        <label>17</label>
                        <mixed-citation publication-type="journal">Lopez De Leon A, Rojkind M. A simple micromethod for collagen and total protein determination in formalinfixed parraffin-embedded sections. J Histochem Cytochem 1985;33: 737-43.</mixed-citation>
                    </ref>
                                    <ref id="ref18">
                        <label>18</label>
                        <mixed-citation publication-type="journal">O’Shea JJ, Murray PJ. Cytokine signaling modules in inflammatory responses. Immunity 2008;28:477–87.</mixed-citation>
                    </ref>
                                    <ref id="ref19">
                        <label>19</label>
                        <mixed-citation publication-type="journal">Amini-Shirazi N, Hoseini A, Ranjbar A, Mohammadirad A, Khoshakhlagh P, Yasa N, Abdollahi M. Inhibition of tumor necrosis factor and nitrosative/oxidative stresses by Ziziphora clinopoides (Kahlioti); a molecular mechanism of protection against dextran sodium sulfate-induced colitis in mice. Toxicol Mech Methods 2009;19:183–9.</mixed-citation>
                    </ref>
                                    <ref id="ref20">
                        <label>20</label>
                        <mixed-citation publication-type="journal">Cetinel S, Hancioğlu S, Sener E, Uner C, Kiliç M, Sener G, Yeğen BC . Oxytocin treatment alleviates stress-aggravated colitis by a receptor-dependent mechanism. Regul Pept 2010;160:146-52.</mixed-citation>
                    </ref>
                                    <ref id="ref21">
                        <label>21</label>
                        <mixed-citation publication-type="journal">Emekli-Alturfan E, Yarat A, Tunali-Akbay T, Isik F, Yenidogan G, Sener G, Sehirli O, Pisiriciler R, Ak E, Altintas A. Effect of Black Cumin (Nigella Sativa) Seed Oil on Gastric Tissue in Experimental Colitis. Adv Environ Biol 2011;5:483-90.</mixed-citation>
                    </ref>
                                    <ref id="ref22">
                        <label>22</label>
                        <mixed-citation publication-type="journal">Şehirli AÖ, Tatlıdede E, Yüksel M, Çetinel Ş, Erzik C, Yeğen B, Şener G. Protective effects of alpha-lipoic acid against oxidative injury in TNBS-induced colitis. Erciyes Med J 2009;31:15-26.</mixed-citation>
                    </ref>
                                    <ref id="ref23">
                        <label>23</label>
                        <mixed-citation publication-type="journal">Ross D. Glutathione, free radicals and chemotherapeutic agents. Mechanisms of free-radical induced toxicity and glutathione-dependent protection. Pharmacol Ther 1988;37:231–49.</mixed-citation>
                    </ref>
                                    <ref id="ref24">
                        <label>24</label>
                        <mixed-citation publication-type="journal">Reiter RJ, Tan DX, Osuna C, Gitto E. Actions of melatonin in the reduction of oxidative stress. A review. J Biomed Sci 2000;7:444–58.</mixed-citation>
                    </ref>
                                    <ref id="ref25">
                        <label>25</label>
                        <mixed-citation publication-type="journal">Elson CO, Sartor RB, Tennyson GS, Riddell RH. Experimental models of inflammatory bowel disease. Gastroenterology 1995;109:1344–67.</mixed-citation>
                    </ref>
                                    <ref id="ref26">
                        <label>26</label>
                        <mixed-citation publication-type="journal">Işeri SO, Sener G, Sağlam B, Gedik N, Ercan F, Yeğen BC. Oxytocin ameliorates oxidative colonic inflammation by a neutrophil-dependent mechanism. Peptides. 2005;26:483-91.</mixed-citation>
                    </ref>
                                    <ref id="ref27">
                        <label>27</label>
                        <mixed-citation publication-type="journal">Jahovic N, Gedik N, Ercan F, Sirvanci S, Yüksel M, Sener G, Alican I.Effects of statins on experimental colitis in normocholesterolemic rats. Scand J Gastroenterol. 2006;41:954-62.</mixed-citation>
                    </ref>
                            </ref-list>
                    </back>
    </article>
