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            <front>

                <journal-meta>
                                                                <journal-id>harran univ vet fak derg</journal-id>
            <journal-title-group>
                                                                                    <journal-title>Harran University Journal of the Faculty of Veterinary Medicine</journal-title>
            </journal-title-group>
                                        <issn pub-type="epub">2146-7188</issn>
                                                                                            <publisher>
                    <publisher-name>Harran University</publisher-name>
                </publisher>
                    </journal-meta>
                <article-meta>
                                        <article-id pub-id-type="doi">10.31196/huvfd.508862</article-id>
                                                                <article-categories>
                                            <subj-group  xml:lang="en">
                                                            <subject>Zootechny (Other)</subject>
                                                    </subj-group>
                                            <subj-group  xml:lang="tr">
                                                            <subject>Hayvansal Üretim (Diğer)</subject>
                                                    </subj-group>
                                    </article-categories>
                                                                                                                                                        <title-group>
                                                                                                                        <article-title>Effects of Oleuropein on Hyperglycemia, Total Oxidant and Antioxidant Capacity in Streptozotosin-Diabetic Rats Treated with Metformin and Insulin</article-title>
                                                                                                                                                                                                <trans-title-group xml:lang="tr">
                                    <trans-title>Streptozotosin ile Diyabet Oluşturulmuş ve Metformin-İnsülin ile Diyabet Tedavisi Gören Ratlarda, Oleuropeinin Hiperglisemi, Total Oksidan ve Total Antioksidan Düzeyleri Üzerine Etkileri</trans-title>
                                </trans-title-group>
                                                                                                    </title-group>
            
                                                    <contrib-group content-type="authors">
                                                                        <contrib contrib-type="author">
                                                                <name>
                                    <surname>Kamiloğlu</surname>
                                    <given-names>Nadide Nabil</given-names>
                                </name>
                                                                    <aff>Department of Physiology, Faculty of Veterinary Medicine, Kafkas University, 36300, Kars, Turkey</aff>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                <name>
                                    <surname>Dağdelen Hastürk</surname>
                                    <given-names>Hülya</given-names>
                                </name>
                                                                    <aff>Department of Physiology, Health Sciences Institute, Kafkas University, 36300, Kars, Turkey</aff>
                                                            </contrib>
                                                                                </contrib-group>
                        
                                        <pub-date pub-type="pub" iso-8601-date="20181227">
                    <day>12</day>
                    <month>27</month>
                    <year>2018</year>
                </pub-date>
                                        <volume>7</volume>
                                        <issue>2</issue>
                                        <fpage>138</fpage>
                                        <lpage>143</lpage>
                        
                        <history>
                                    <date date-type="received" iso-8601-date="20180328">
                        <day>03</day>
                        <month>28</month>
                        <year>2018</year>
                    </date>
                                                    <date date-type="accepted" iso-8601-date="20181125">
                        <day>11</day>
                        <month>25</month>
                        <year>2018</year>
                    </date>
                            </history>
                                        <permissions>
                    <copyright-statement>Copyright © 2012, Harran University Journal of the Faculty of Veterinary Medicine</copyright-statement>
                    <copyright-year>2012</copyright-year>
                    <copyright-holder>Harran University Journal of the Faculty of Veterinary Medicine</copyright-holder>
                </permissions>
            
                                                                                                <abstract><p>In thisstudy, it was aimed to investigate the effects of oleuropein on hyperglycemiaand oxidant-antioxidant levels in metformin-insulin treatedstreptozotocin-diabetic rats. For this purpose, 40 Sprague-Dawley rats wereused. Animals were divided into 5 groups as 4 experimental and 1 Control each containing8 rats. 1 ml isotonic NaCl solution was injected intraperitoneally (ip) to the Controlgroup while 50 mg/kg STZ ip was given to the G1, 50 mg/kg STZ + 100 mg/kgMetformin + 4 IU/kg insulin ip was given to the G2, 50 mg/kg STZ + 100 mg/kgMetformin + 4 IU/kg insulin ip and 30 mg/kg orally oleuropein was given to the G3and 50 mg/kg STZ ip and 30 mg/kg oleuropein orally was given to the G4. Bloodglucose values were statistically higher in the experimental groups than thecontrol after streptozotocin administration (P&amp;lt;0.001, P&amp;lt;0.01, P&amp;lt;0.01respectively). Plasma Total Antioxidant Capacity (TAC) of G2 and G3 were statistically higher thanG1 (P&amp;lt;0.001). It was found that plasma TAC levels of G3 were statisticallyhigher than the control (P&amp;lt;0.05). It was determined that the G1(P&amp;lt;0.001), G2 (P&amp;lt;0.01) and G3 (P&amp;lt;0.05) group had significantly higherplasma Total Oxidant Capacity (TOC) than the control group. TAC levels in theliver of the experimental groups were determined to be statisticallyinsignificant according to the control group. The liver TOC levels of the G2and G4 group were significantly higher than the control group (P&amp;lt;0.01, P&amp;lt;0.001respectively). In conclusion, the use of oleuropein alone did not affect theblood glucose level, the live weight, the plasma and the liver TAC and TOClevels, but the use of metformin and insulin with oleuropein as an antioxidantand free radical scavenger following to the rising oxidation in diabetes weresupported and strengthen the system.</p></abstract>
                                                                                                                                    <trans-abstract xml:lang="tr">
                            <p>Bu çalışmada,streptozotosin ile diyabet oluşturulmuş ve metformin ve insülin ile diyabettedavisi gören ratlarda, oleuropeinin hiperglisemi, oksidan-antioksidandüzeyleri üzerine etkilerinin araştırılması amaçlandı. Bu maksatla, 40 adeterkek Sprague Dawley rat kullanıldı. Ratlar her grupta 8 hayvan bulunacakşekilde 4 deney ve 1 kontrol grubu olmak üzere 5 gruba ayrıldı. Kontrol grubuna%0.09 NaCl intraperitoneal (ip) uygulandı. G1’e 50 mg/kg STZ ip, G2’ye 50 mg/kgSTZ + 100 mg/kg metformin + 4 İU/kg insülin ip, G3’e 50 mg/kg STZ + 100 mg/kgmetformin + 4 İU/kg insülin ip ve 30 mg/kg oleuropein oral olarak ve G4’e 50mg/kg STZ ip olarak ve 30 mg/kg oleuropein oral olarak uygulandı. Streptozotosinuygulandıktan sonraki 3, 10 ve 21. günlerde deneme gruplarının kan glukozdeğerleri kontrol grubuna göre istatistiksel olarak önemli düzeyde yüksekbulunmuştur (sırasıyla P&amp;lt;0.001, P&amp;lt;0.01, P&amp;lt;0.01). Plazma totalantioksidan kapasiteleri gruplar arasında kıyaslandığında, G2 ve G3 grubunun TotalAntioksidan Kapasite (TAC) düzeyleri, G1 grubuna göre istatistiksel olarak dahayüksek belirlenmiştir (P&amp;lt;0.001). Kontrol grubu ile deneme gurupları arasındakıyaslama yapıldığında G3 grubunun TAC düzeylerinin, kontrol grubuna göreistatistiksel olarak yüksek olduğu belirlenmiştir (P&amp;lt;0.05). G1 (P&amp;lt;0.001),G2 (P&amp;lt;0.01) ve G3 (P&amp;lt;0.05) grubunun plazma Total Oksidan Kapasitelerinin(TOC) kontrol grubuna göre istatistiksel olarak yüksek olduğu belirlenmiştir.Deneme gruplarının karaciğer TAC düzeylerinin kontrol grubuna göreistatistiksel olarak önemsiz olduğu tespit edildi. Karaciğer total oksidankapasiteleri gruplar arasında kıyaslandığında G2 grubu ile G4 gurubunun TOCdüzeylerinin kontrol grubuna göre istatistiksel olarak yüksek olduğu (sırasıylaP&amp;lt;0.01, P&amp;lt;0.001) belirlenmiştir. Sonuç olarak oleuropeinin tek başınakullanımının kan glukoz düzeyini, canlı ağırlığı ve plazma ile karaciğer TAC veTOC kapasitelerini etkilemediği, ancak diyabette yükselen oksidasyona karşılık,metformin ve insülinle birlikte kullanımının antioksidan sisteme destek olduğuve serbest radikal tutucu etkiyi kuvvetlendirdiği düşünülmektedir.</p></trans-abstract>
                                                            
            
                                                            <kwd-group>
                                                    <kwd>Diabet</kwd>
                                                    <kwd>  Insulin</kwd>
                                                    <kwd>  Metformine</kwd>
                                                    <kwd>  Oleuropein</kwd>
                                                    <kwd>  TAC</kwd>
                                                    <kwd>  TOC</kwd>
                                            </kwd-group>
                                                        
                                                                            <kwd-group xml:lang="tr">
                                                    <kwd>Diabet</kwd>
                                                    <kwd>  İnsulin</kwd>
                                                    <kwd>  Metformine</kwd>
                                                    <kwd>  Oleuropein</kwd>
                                                    <kwd>  TAC</kwd>
                                                    <kwd>  TOC</kwd>
                                            </kwd-group>
                                                                                                            </article-meta>
    </front>
    <back>
                            <ref-list>
                                    <ref id="ref1">
                        <label>1</label>
                        <mixed-citation publication-type="journal">Abou-Seif MA, Youssef AA, 2004: Evaluation of some biochemical changes in diabetic patients. Clinica Chimica Acta, 346, 161–170.</mixed-citation>
                    </ref>
                                    <ref id="ref2">
                        <label>2</label>
                        <mixed-citation publication-type="journal">Al-Azzawie HF, Alhamdani MS, 2006: Hypoglycemic and antioxidant effect of oleuropein in alloxan-diabetic rabbits. Life Sci, 78, 1371-1377.</mixed-citation>
                    </ref>
                                    <ref id="ref3">
                        <label>3</label>
                        <mixed-citation publication-type="journal">American Diabetes Association (ADA) 2005: Standards of medical care in diabetes, Diabetes Care 28, 34-36.</mixed-citation>
                    </ref>
                                    <ref id="ref4">
                        <label>4</label>
                        <mixed-citation publication-type="journal">Asgary S, Naderi GA, Sarraf ZN, Vakili R, 2002: The inhibitory effects of pure flavonoids on in vitro protein glycosylation. J Herb Pharmacother, 2, 47–55.</mixed-citation>
                    </ref>
                                    <ref id="ref5">
                        <label>5</label>
                        <mixed-citation publication-type="journal">Aslan M, Orhan DD, Orhan N, Sezik E, Yeşilada E, 2007: In vivo antidiabetic and antioxidant potential of Helichrysum plicantaum ssp. Plicatum capitulums in streptozotocin-induced-diabetic rats. J Ethonopharmacol, 109, 54–59.</mixed-citation>
                    </ref>
                                    <ref id="ref6">
                        <label>6</label>
                        <mixed-citation publication-type="journal">Cusi K, DeFronzo RA, 1998: Metformin: a review of its metabolic effects. Diabetes Rev, 6, 89-131.</mixed-citation>
                    </ref>
                                    <ref id="ref7">
                        <label>7</label>
                        <mixed-citation publication-type="journal">Davie SJ, Gould BJ, Yudkin JS, 1992: Effect of vitamin C on glycosylation of proteins. Diabetes, 41, 167–173.</mixed-citation>
                    </ref>
                                    <ref id="ref8">
                        <label>8</label>
                        <mixed-citation publication-type="journal">Emanuelli B, Glondu M, Filloux C, Peraldi P, Obberghen EV, 2004:  The potential role of SOCS-3 in the interleukin-induced desensitization of insulin signaling in pancreatic-cells. Diabetes, 53, 97-103.</mixed-citation>
                    </ref>
                                    <ref id="ref9">
                        <label>9</label>
                        <mixed-citation publication-type="journal">Farah R, Shurtz-Swirski R, Lapin O, 2008: Intensification of oxidative stress and inflammation in Type 2 diabetes despite antihyperglycemic treatment. Cardiovasc Diabetol, 7, 20.</mixed-citation>
                    </ref>
                                    <ref id="ref10">
                        <label>10</label>
                        <mixed-citation publication-type="journal">Galli C, Visioli F, 1999: Antioxidant and other activities of phenolics in olives/olive oil, typical components of the mediterranean diet. Lipids, 34, 23-26.</mixed-citation>
                    </ref>
                                    <ref id="ref11">
                        <label>11</label>
                        <mixed-citation publication-type="journal">Garrido-Fernandez A, Fernandez-Diez MJ, Adams MR, 1997: Table Olives: Production and Processing. 1st ed., 495, Chapman &amp; Hall, London, UK.</mixed-citation>
                    </ref>
                                    <ref id="ref12">
                        <label>12</label>
                        <mixed-citation publication-type="journal">Kumar RS, Anthrayose CV, Iyer KV, Vimala B, Shashidhar S, 2001: Lipid peroxidation and diabetic retinopathy. Indian Med Sci, 55, 133-138.</mixed-citation>
                    </ref>
                                    <ref id="ref13">
                        <label>13</label>
                        <mixed-citation publication-type="journal">Lean ME, Noroozi M, Kelly I, Burns J, Talwar D, Sattar N, Crozier A, 1999: Dietary flavonols protect diabetic human lymphocytes against oxidative damage to DNA. Diabetes, 48, 176–181.</mixed-citation>
                    </ref>
                                    <ref id="ref14">
                        <label>14</label>
                        <mixed-citation publication-type="journal">Lee MS, Hsu CC, Wahlqvist ML, Tsai HN, Chang YH, Huang YC, 2011: Type 2 diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in Taiwanese: a representative population prospective cohort study of 800,000 individuals. BMC Cancer, 11, 20.</mixed-citation>
                    </ref>
                                    <ref id="ref15">
                        <label>15</label>
                        <mixed-citation publication-type="journal">Lee SH, Kwon KI, 2004: Pharmacokinetic-pharmacodynamic modeling for the relationship between glucose-lowering effect and plasma concentration of metformin in volunteers. Arch Pharm Res, 27, 806-810.</mixed-citation>
                    </ref>
                                    <ref id="ref16">
                        <label>16</label>
                        <mixed-citation publication-type="journal">Lhommeau I, Douillard S, Bigot E, Benoit I, Krempf M, Patrice T, 2011: Serum resistance to singlet oxygen in patients with diabetes mellitus in comparison to healthy donors. Metabolism, 60, 1340-1348,</mixed-citation>
                    </ref>
                                    <ref id="ref17">
                        <label>17</label>
                        <mixed-citation publication-type="journal">Li X, Zhang N, Li Y, Shi Y, Li D, Xie Y, Ming J, 2011: Effects of metformin and rosiglitazone on peripheral insulin resistance and β-cell function in obesity: a double-blind, randomized, controlled study. J Int Med Res, 39, 358-365.</mixed-citation>
                    </ref>
                                    <ref id="ref18">
                        <label>18</label>
                        <mixed-citation publication-type="journal">Montes-Cortes DH, Hicks JJ, Ceballos-Reyes GM, Garcia-Sanchez JR, Medina-Navarro R, Olivares-Corichi IM, 2010: Chemical and functional changes of human insulin by in vitro incubation with blood from diabetic patients in oxidative stres. Metabolism, 59, 935-942.</mixed-citation>
                    </ref>
                                    <ref id="ref19">
                        <label>19</label>
                        <mixed-citation publication-type="journal">Niwa A, Tajiri T, Higashino H, 2011: Ipomoea batatas and agarics blazei ameliorate diabetic disorders with therapeutic antioxidant potential in streptozotocininduced diabetic rats. J Clin Biochem Nutr, 48, 194-202.</mixed-citation>
                    </ref>
                                    <ref id="ref20">
                        <label>20</label>
                        <mixed-citation publication-type="journal">Novelli M, Fabregat ME, Fernandez-Alvarez J, Gomis R, Masiello P, 2001: Metabolic and functional studies on isolated islets in a new rat model of Type 2 diabetes. Molecular and Cell Endocrin, 175, 57-66.</mixed-citation>
                    </ref>
                                    <ref id="ref21">
                        <label>21</label>
                        <mixed-citation publication-type="journal">Novelli M, Pocai A, Lajoix AD, Beffy P, Bezi D, Marchetti P, Gross R, Masiello P, 2004: Alteration of β-cell constitutive NO synthase activity is involved in the abnormal insulin response to arginine in a new rat model of Type 2 diabetes. Mol Cell Endocrin, 219, 77-82.</mixed-citation>
                    </ref>
                                    <ref id="ref22">
                        <label>22</label>
                        <mixed-citation publication-type="journal">Özata M, Yönem A, 2006: Endokrinoloji Metabolizma ve Diyabet. 1st ed., 275-343, İstanbul Medikal Yayıncılık, İstanbul, Türkiye.</mixed-citation>
                    </ref>
                                    <ref id="ref23">
                        <label>23</label>
                        <mixed-citation publication-type="journal">Pan HZ, Zhang H, Chang D, Li H, Sui H, 2008: The change of oxidative stress products in diabetes mellitus and diabetic retinopathy. Br J Ophthalmol, 92, 548–551.</mixed-citation>
                    </ref>
                                    <ref id="ref24">
                        <label>24</label>
                        <mixed-citation publication-type="journal">Pirie FJ, Omar M, Motala AA, Amod A, 1996: The Genetics of non insulin dependent diabetes mellitus (NIDDM) in Africa. Int J Dia Dev Count, 16, 36-40.</mixed-citation>
                    </ref>
                                    <ref id="ref25">
                        <label>25</label>
                        <mixed-citation publication-type="journal">Schneider J, 1991: Effects of metformin on dyslipoproteinemia in non-insulindependent diabetes mellitus. Diabet Metab, 17, 185-190.</mixed-citation>
                    </ref>
                                    <ref id="ref26">
                        <label>26</label>
                        <mixed-citation publication-type="journal">Sheetz MJ, King GL, 2002: Molecular understanding of hyperglycemia&#039;s adverse effects for diabetic complications. JAMA, 288, 2579–2588.</mixed-citation>
                    </ref>
                                    <ref id="ref27">
                        <label>27</label>
                        <mixed-citation publication-type="journal">Sinclair AJ, Girling AJ, Gray L, Lunec J, Barnett AH, 1992: An investigatio of the relationship between free radical activity and vitamin C metabolism in elderly diabetic subjects with retinopathy. Gerontology, 38, 268–274.</mixed-citation>
                    </ref>
                                    <ref id="ref28">
                        <label>28</label>
                        <mixed-citation publication-type="journal">Singh I, Mok M, Christensen AM, Turner AH, Hawley JA, 2008: The effects of polyphenols in olive leaves on platelet function. Nutr Metab Cardiovasc Diseas, 18, 127-132.</mixed-citation>
                    </ref>
                                    <ref id="ref29">
                        <label>29</label>
                        <mixed-citation publication-type="journal">Sliwinska A, Blasiak J, Drzewoski J, 2006: Effect of gliclazide on DNA damage in human peripheral blood lymphocytes and insulinoma mouse cells. Chem-Bioll Interact, 162, 259-267.</mixed-citation>
                    </ref>
                                    <ref id="ref30">
                        <label>30</label>
                        <mixed-citation publication-type="journal">Stepensky D, Friedman M, Raz I, Hoffman A, 2002: Pharmacokinetic pharmacodynamic analysis of the glucose-lowering effect of metformin in diabetic rats reveals first-pass pharmacodynamic effect. Drug Metab Dispos, 30, 861-868.</mixed-citation>
                    </ref>
                                    <ref id="ref31">
                        <label>31</label>
                        <mixed-citation publication-type="journal">Tetik HD, 2005: Sofralık Zeytin İşleme Teknikleri. 5th ed., 136, Emre Basımevi, İzmir, Türkiye.</mixed-citation>
                    </ref>
                                    <ref id="ref32">
                        <label>32</label>
                        <mixed-citation publication-type="journal">Tripoli E, Giammanco M, Tabacchi G, Majo DD, Giammanco S, Guardia LM, 2005: The phenolic compounds of olive oil: structure, biological activity and beneficial effects on human health. NutrRes Rev, 18, 112.</mixed-citation>
                    </ref>
                                    <ref id="ref33">
                        <label>33</label>
                        <mixed-citation publication-type="journal">Tsimidou M, 1998: Polyphenols and quality of virgin olive oil in retrospect. Ital J Food Sci, 10, 99-116.</mixed-citation>
                    </ref>
                                    <ref id="ref34">
                        <label>34</label>
                        <mixed-citation publication-type="journal">Üstüner MC, 1999: The Effects of Acarbose and Rumex Patientia L. (Labada) in Experimental Animals with Type II Diabetes. Yüksek Lisans Tezi, OGÜ Sağlık Bilimleri Enstitüsü, Eskişehir.</mixed-citation>
                    </ref>
                                    <ref id="ref35">
                        <label>35</label>
                        <mixed-citation publication-type="journal">Visioli F, Galli C, 1994: Oleuropein protects LDL from oxidation. Life Sci, 55, 1965-971.</mixed-citation>
                    </ref>
                                    <ref id="ref36">
                        <label>36</label>
                        <mixed-citation publication-type="journal">Visioli F, Galli C, 1995: Natural antioxidants and prevention of coronary heart disease: the potential role of olive oil and its minor constituents. Nutr Metab Cardovasc Dis, 5, 306-331.</mixed-citation>
                    </ref>
                                    <ref id="ref37">
                        <label>37</label>
                        <mixed-citation publication-type="journal">Vlahov G, 1992: Flavonoids in three olive (Olea europaea) fruit varieties during maturation. J Sci Food Agric, 58, 157-159.</mixed-citation>
                    </ref>
                                    <ref id="ref38">
                        <label>38</label>
                        <mixed-citation publication-type="journal">Wolff SP, 1993: Diabetes mellitus and free radicals: Free radicals, transition metals and oxidative stress in the etiology of diabetes mellitus and complications. British Medical Bulletin, 49, 642-52.</mixed-citation>
                    </ref>
                                    <ref id="ref39">
                        <label>39</label>
                        <mixed-citation publication-type="journal">Xie Z, Zhang J, Wu J, Viollet B, Ming-Hui Z, 2008: Upregulation of mitochondrial uncoupling protein-2 by the AMP-activated protein kinase in endothelial cells attenuates oxidative stress in diabetes. Diabetes, 57, 3222–3230.</mixed-citation>
                    </ref>
                                    <ref id="ref40">
                        <label>40</label>
                        <mixed-citation publication-type="journal">Yenigün M, 2001: Her Yönü ile diabetes mellitus. 1st ed., 8-80, Nobel Tıp, İstanbul, Türkiye.</mixed-citation>
                    </ref>
                            </ref-list>
                    </back>
    </article>
