{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T23:11:14Z","timestamp":1765667474282,"version":"3.37.3"},"reference-count":67,"publisher":"Georg Thieme Verlag KG","issue":"06","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Res (Stuttg)"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Introduction Gastric ulcer is one of the most common and serious\n                    conditions in the gastrointestinal tract. One of the main causes of gastric\n                    ulcers is using of non-steroidal anti-inflammatory drugs (NSAIDs) which have\n                    limited their use in clinical practice. Several studies have revealed that\n                    metformin and Vitamin C (Vit C) exhibit protective effects against gastric\n                    mucosal damage in different animal models. However, no studies indicate their\n                    combination's effect on gastric ulcer models. Therefore, this study aims to\n                    investigate the protective effects of metformin and Vit C combination on\n                    indomethacin-induced gastric ulcers.<\/jats:p><jats:p>\n          Material and methods In total, thirty rats were divided into six groups,\n                    including the control group, rats received indomethacin (50\u2009mg\/kg, i.p.), rats\n                    received indomethacin and pretreated with ranitidine (100\u2009mg\/kg), metformin\n                    (100\u2009mg\/kg, i.p.), Vit C (100\u2009mg\/kg), or metformin combined with Vit C. Four\n                    hours after indomethacin administration, rats were euthanized, and gastric\n                    tissues were removed for macroscopic, histopathologic, and biochemical\n                    examinations.<\/jats:p><jats:p>\n          Results All therapeutics used in this study were found to alleviate\n                    gastric mucosal injury caused by indomethacin, as observed in histopathologic\n                    and macroscopic evaluations. Both Vit C and metformin were observed to\n                    significantly decrease lipid peroxidation and enhance the activity of\n                    anti-oxidative enzymes, SOD, GPx, and catalase. However, a more significant\n                    effectiveness was observed in catalase and GPx activities when Vit C was\n                    co-administered with metformin.<\/jats:p><jats:p>\n          Conclusions In conclusion, the present study revealed that metformin and\n                    Vit C combination therapy could potentially treat gastric ulcers associated with\n                    indomethacin.<\/jats:p>","DOI":"10.1055\/a-2317-7578","type":"journal-article","created":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T23:29:25Z","timestamp":1720222165000},"page":"280-289","source":"Crossref","is-referenced-by-count":2,"title":["Concomitant Effects of Metformin and Vitamin C on\n                    Indomethacin-Induced Gastric Ulcer in Rats: Biochemical and Histopathological\n                    Approach"],"prefix":"10.1055","volume":"74","author":[{"given":"Mohammad Rafi","family":"Khezri","sequence":"additional","affiliation":[{"name":"Student Research Committee, Urmia University of Medical Sciences,\n                    Urmia, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reza","family":"Varzandeh","sequence":"additional","affiliation":[{"name":"Student Research Committee, Urmia University of Medical Sciences,\n                    Urmia, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5672-9202","authenticated-orcid":false,"given":"Morteza","family":"Ghasemnejad-Berenji","sequence":"additional","affiliation":[{"name":"Experimental & Applied Pharmaceutical Sciences Research Center,\n                    Urmia University of Medical Sciences, Urmia, Iran"},{"name":"Department of Pharmacology and Toxicology, School of Pharmacy, Urmia\n                    University of Medical Sciences,Urmia, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2024,7,5]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"580","DOI":"10.3109\/1547691X.2016.1142488","article-title":"Nebivolol prevents indomethacin-induced gastric ulcer in rats","volume":"13","author":"N E El-Ashmawy","year":"2016","journal-title":"J Immunotoxicol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1163\/156856002321544765","article-title":"Mechanisms of peptic ulcer recurrence: role of inflammation","volume":"10","author":"T Watanabe","year":"2002","journal-title":"InflammoPharmacology"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"43","DOI":"10.2174\/1568010043483971","article-title":"Novel non-steroidal anti-inflammatory drugs: what we have learned from animal\n                    studies","volume":"3","author":"G Coruzzi","year":"2004","journal-title":"Curr Drug Targets Inflamm Allergy"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"131","DOI":"10.7861\/clinmed.2021-0039","article-title":"Non-steroidal anti-inflammatory drugs and the gastrointestinal tract","volume":"21","author":"FW D Tai","year":"2021","journal-title":"Clinical Medicine"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"3705","DOI":"10.3748\/wjg.v13.i27.3705","article-title":"Healing property of the Piper betel phenol, allylpyrocatechol against\n                    indomethacin-induced stomach ulceration and mechanism of action","volume":"13","author":"S Bhattacharya","year":"2007","journal-title":"World J Gastroenterol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1124\/pr.56.3.3","article-title":"Cyclooxygenase isozymes: the biology of prostaglandin synthesis and\n                    inhibition","volume":"56","author":"D L Simmons","year":"2004","journal-title":"Pharmacol Rev"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.lfs.2019.03.054","article-title":"Safranal, a constituent of saffron, exerts gastro-protective effects against\n                    indomethacin-induced gastric ulcer","volume":"224","author":"E Tamaddonfard","year":"2019","journal-title":"Life sciences"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"829","DOI":"10.3390\/biomedicines11030829","article-title":"Carnosic Acid Ameliorates Indomethacin-Induced Gastric Ulceration in Rats by\n                    Alleviating Oxidative Stress and Inflammation","volume":"11","author":"B Danisman","year":"2023","journal-title":"Biomedicines"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"114752","DOI":"10.1016\/j.jep.2021.114752","article-title":"Chinese sumac (Rhus chinensis Mill.) fruits alleviate indomethacin-induced\n                    gastric ulcer in mice by improving oxidative stress, inflammation and\n                    apoptosis","volume":"284","author":"N Ma","year":"2022","journal-title":"J Ethnopharmacol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"173812","DOI":"10.1016\/j.ejphar.2020.173812","article-title":"The effect of metformin on indomethacin-induced gastric ulcer: Involvement of\n                    nitric oxide\/Rho kinase pathway","volume":"892","author":"E Y AbdelAziz","year":"2021","journal-title":"Eur J Pharmacol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/j.1440-1681.2009.05250.x","article-title":"Gastroprotective effects of the insulin sensitizers rosiglitazone and metformin\n                    against indomethacin-induced gastric ulcers in Type 2 diabetic rats","volume":"37","author":"M A Morsy","year":"2010","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.metabol.2015.10.014","article-title":"Metformin-associated lactic acidosis: Current perspectives on causes and\n                    risk","volume":"65","author":"R DeFronzo","year":"2016","journal-title":"Metabolism"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1161\/01.ATV.0000203525.62147.28","article-title":"Oxidative stress and vascular disease: 2005 Duff lecture","volume":"26","author":"D D Heistad","year":"2006","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1293\/tox.26.111","article-title":"Antioxidant Activity of Tocotrienol Rich Fraction Prevents Fenitrothion-induced\n                    Renal Damage in Rats","volume":"26","author":"S B Budin","year":"2013","journal-title":"J Toxicol Pathol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"3290","DOI":"10.1016\/j.fct.2008.07.015","article-title":"Effects of dietary vitamin E, C and soybean oil supplementation on antioxidant\n                    enzyme activities in liver and muscles of rats","volume":"46","author":"K F Shireen","year":"2008","journal-title":"Food Chem Toxicol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1146\/annurev.nu.14.070194.002103","article-title":"Pharmacology of vitamin C","volume":"14","author":"H E Sauberlich","year":"1994","journal-title":"Annu Rev Nutr"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1475-2891-2-7","article-title":"Vitamin C in human health and disease is still a mystery? An overview","volume":"2","author":"K A Naidu","year":"2003","journal-title":"Nutr J"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1096\/fasebj.13.9.1007","article-title":"Does vitamin C act as a pro-oxidant under physiological conditions?","volume":"13","author":"A Carr","year":"1999","journal-title":"Faseb j"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1177\/0748233712468020","article-title":"Protective effects of vitamin C and selenium supplementation on methomyl-induced\n                    tissue oxidative stress in adult rats","volume":"31","author":"A Djeffal","year":"2015","journal-title":"Toxicol Ind Health"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"7514","DOI":"10.1021\/jf049243r","article-title":"Protective effects of quercetin and vitamin C against oxidative stress-induced\n                    neurodegeneration","volume":"52","author":"H J Heo","year":"2004","journal-title":"J Agric Food Chem"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1080\/08923973.2023.2181712","article-title":"The effect of vitamin C supplementation on favipiravir-induced oxidative stress\n                    and proinflammatory damage in livers and kidneys of rats","volume":"45","author":"M F Do\u011fan","year":"2023","journal-title":"Immunopharmacol Immunotoxicol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"135","DOI":"10.3177\/jnsv.51.135","article-title":"Effects of astaxanthin and vitamin C on the prevention of gastric ulcerations in\n                    stressed rats","volume":"51","author":"Y Nishikawa","year":"2005","journal-title":"J Nutr Sci Vitaminol (Tokyo)"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"76","DOI":"10.14715\/cmb\/2019.65.3.11","article-title":"The effects of antioxidant combination on indomethacin-induced gastric mucosal\n                    injury in rats","volume":"65","author":"I B Turkyilmaz","year":"2019","journal-title":"Cellular and Molecular Biology"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"767","DOI":"10.5152\/tjg.2022.21195","article-title":"The Effect of Metformin on Ethanol- and IndomethacinInduced Gastric Ulcers in\n                    Rats","volume":"33","author":"B E \u0130pek","year":"2022","journal-title":"Turk J Gastroenterol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/bcpt.13492","article-title":"BCPT policy for experimental and clinical studies","volume":"128","author":"P Tveden-Nyborg","year":"2021","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1139\/cjpp-2017-0730","article-title":"The gastroprotective effect of N-acetylcysteine and genistein in\n                    indomethacin-induced gastric injury in rats","volume":"96","author":"I I Hegab","year":"2018","journal-title":"Can J Physiol Pharmacol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1007\/s12011-008-8205-9","article-title":"Gastroprotective and anti-oxidative properties of ascorbic acid on\n                    indomethacin-induced gastric injuries in rats","volume":"126","author":"M Koc","year":"2008","journal-title":"Biological trace element research"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1111\/bcpt.13718","article-title":"Gastroprotective effect of topiramate on indomethacin-induced peptic ulcer in\n                    rats: Biochemical and histological analyses","volume":"130","author":"A Jafari","year":"2022","journal-title":"Basic & Clinical Pharmacology & Toxicology"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.intimp.2016.06.016","article-title":"Anti-ulcerogenic effect of cavidine against ethanol-induced acute gastric ulcer\n                    in mice and possible underlying mechanism","volume":"38","author":"W Li","year":"2016","journal-title":"International immunopharmacology"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"2618","DOI":"10.3390\/md10122618","article-title":"A sulfated-polysaccharide fraction from seaweed Gracilaria birdiae prevents\n                    naproxen-induced gastrointestinal damage in rats","volume":"10","author":"R O Silva","year":"2012","journal-title":"Marine drugs"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"112254","DOI":"10.1016\/j.biopha.2021.112254","article-title":"Yiqi Tongluo Fang could preventive and delayed development and formation of\n                    diabetic retinopathy through antioxidant and anti-inflammatory effects","volume":"148","author":"S Di","year":"2022","journal-title":"Biomedicine & Pharmacotherapy"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.ajem.2020.03.060","article-title":"Topiramate: A novel protective agent against ischemia reperfusion-induced\n                    oxidative injury after testicular torsion\/detorsion","volume":"44","author":"A Jafari","year":"2021","journal-title":"The American journal of emergency medicine"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.biopha.2018.06.012","article-title":"Synergistic effect of rapamycin and metformin against germ cell apoptosis and\n                    oxidative stress after testicular torsion\/detorsion-induced ischemia\/reperfusion\n                    in rats","volume":"105","author":"M Ghasemnejad-Berenji","year":"2018","journal-title":"Biomedicine & Pharmacotherapy"},{"key":"ref34","first-page":"427","volume-title":"Quercetin protects against lipopolysaccharide-induced acute lung injury in rats\n                    through suppression of inflammation and oxidative stress","author":"R Huang","year":"2015"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","article-title":"Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction","volume":"95","author":"H Ohkawa","year":"1979","journal-title":"Analytical biochemistry"},{"key":"ref36","first-page":"91","article-title":"Free radicals, antioxidants, diseases and phytomedicines: current status and\n                    future prospect","volume":"3","author":"S Sen","year":"2010","journal-title":"International journal of pharmaceutical sciences review and\n                    research"},{"key":"ref37","first-page":"39","article-title":"Effects of reactive oxygen species action on gastric mucosa in various models of\n                    mucosal injury","volume":"53","author":"S Kwiecien","year":"2002","journal-title":"Journal of physiology and pharmacology"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1023\/A:1005560104847","article-title":"Interaction between NSAIDs and steroid in rat stomach: safety of nimesulide as a\n                    preferential COX-2 inhibitor in the stomach","volume":"45","author":"H Kataoka","year":"2000","journal-title":"Dig Dis Sci"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1023\/A:1014764705864","article-title":"Melatonin prevents ethanol-induced gastric mucosal damage possibly due to its\n                    antioxidant effect","volume":"47","author":"D Bilici","year":"2002","journal-title":"Digestive Diseases and Sciences"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"114331","DOI":"10.1016\/j.biopha.2023.114331","article-title":"Apple (Malus domestica Borkh) leaves attenuate indomethacin-induced gastric\n                    ulcer in rats","volume":"160","author":"M F Mahmoud","year":"2023","journal-title":"Biomedicine & Pharmacotherapy"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.pestbp.2009.04.001","article-title":"Chlorpyrifos induced alterations in the levels of hydrogen peroxide, nitrate and\n                    nitrite in rat brain and liver","volume":"94","author":"A Mehta","year":"2009","journal-title":"Pesticide biochemistry and physiology"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1016\/j.ecoenv.2011.07.001","article-title":"Protective effects of vitamins C and E against hepatotoxicity induced by methyl\n                    parathion in rats","volume":"74","author":"M Uzunhisarcikli","year":"2011","journal-title":"Ecotoxicology and environmental safety"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.ecoenv.2008.04.007","article-title":"Effects of subacute exposure of dichlorvos at sublethal dosages on erythrocyte\n                    and tissue antioxidant defense systems and lipid peroxidation in rats","volume":"72","author":"I Celik","year":"2009","journal-title":"Ecotoxicology and environmental safety"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1007\/s11418-012-0670-y","article-title":"Protective effect of D-002, a mixture of beeswax alcohols, against\n                    indomethacin-induced gastric ulcers and mechanism of action","volume":"67","author":"Y P\u00e9rez","year":"2013","journal-title":"Journal of natural medicines"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.toxrep.2015.01.002","article-title":"Indomethacin-induced gastric ulceration in rats: Protective roles of Spondias\n                    mombin and Ficus exasperata","volume":"2","author":"S Sabiu","year":"2015","journal-title":"Toxicology reports"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/S0009-9120(99)00075-2","article-title":"Antioxidant enzymes and human diseases","volume":"32","author":"J M Mat\u00e9s","year":"1999","journal-title":"Clinical biochemistry"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"7282","DOI":"10.1080\/10408398.2021.1913400","article-title":"Superoxide dismutase: an updated review on its health benefits and industrial\n                    applications","volume":"62","author":"M N Islam","year":"2022","journal-title":"Critical Reviews in Food Science and Nutrition"},{"key":"ref48","first-page":"415","article-title":"Comparison of neuroprotective effects of Melissa officinalis total extract and\n                    its acidic and non-acidic fractions against a \u03b2-induced toxicity","volume":"12","author":"M R Sepand","year":"2013","journal-title":"Iranian journal of pharmaceutical research: IJPR"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.canlet.2004.09.041","article-title":"Chemopreventive and therapeutic effects of curcumin","volume":"223","author":"A Duvoix","year":"2005","journal-title":"Cancer letters"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1002\/(SICI)1099-1263(199607)16:4<305::AID-JAT353>3.0.CO;2-F","article-title":"Additive effect of alcohol and nicotine on lipid peroxidation and antioxidant\n                    defence mechanism in rats","volume":"16","author":"L Ashakumary","year":"1996","journal-title":"Journal of Applied Toxicology"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1081\/PFC-120019901","article-title":"Exposure to low doses of endosulfan and chlorpyrifos modifies endogenous\n                    antioxidants in tissues of rats","volume":"38","author":"F N Bebe","year":"2003","journal-title":"Journal of Environmental Science and Health, Part B"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s13105-013-0241-z","article-title":"Effect of selenium and grape seed extract on indomethacin-induced gastric ulcers\n                    in rats","volume":"69","author":"A M Abbas","year":"2013","journal-title":"Journal of physiology and biochemistry"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.jep.2005.06.043","article-title":"Gastroprotective and antioxidant effects of usnic acid on indomethacin-induced\n                    gastric ulcer in rats","volume":"103","author":"F Odabasoglu","year":"2006","journal-title":"Journal of ethnopharmacology"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.etap.2009.03.012","article-title":"Oral co-administration of \u03b1-lipoic acid, quercetin and captopril prevents\n                    gallium arsenide toxicity in rats","volume":"28","author":"K Bhatt","year":"2009","journal-title":"Environmental toxicology and pharmacology"},{"key":"ref55","first-page":"94","article-title":"Modulation of the tissue defense system by squalene in cyclophosphamide induced\n                    toxicity in rats","volume":"2","author":"S Senthilkumar","year":"2006","journal-title":"Archives of Medical Science"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.cbi.2009.11.004","article-title":"Expression of hepatic antioxidant genes in l-thyroxine-induced hyperthyroid\n                    rats: regulation by vitamin E and curcumin","volume":"183","author":"U Subudhi","year":"2010","journal-title":"Chemico-biological interactions"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"172410","DOI":"10.1016\/j.ejphar.2019.172410","article-title":"Alendronate-induced gastric damage in normoglycemic and hyperglycemic rats is\n                    reversed by metformin","volume":"856","author":"I R Nol\u00eato","year":"2019","journal-title":"European Journal of Pharmacology"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"933","DOI":"10.3389\/fendo.2021.718942","article-title":"A critical review of the evidence that metformin is a putative anti-aging drug\n                    that enhances healthspan and extends lifespan","volume":"12","author":"I Mohammed","year":"2021","journal-title":"Frontiers in endocrinology"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"105258","DOI":"10.1016\/j.pestbp.2022.105258","article-title":"Protective effects of metformin against aluminum phosphide-induced acute\n                    hepato-renal damage in rats: An experimental approach","volume":"188","author":"M R Khezri","year":"2022","journal-title":"Pestic Biochem Physiol"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.biopha.2017.08.020","article-title":"Metformin maintains mucosal integrity in experimental model of colitis by\n                    inhibiting oxidative stress and pro-inflammatory signaling","volume":"94","author":"A Pandey","year":"2017","journal-title":"Biomedicine & Pharmacotherapy"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"16895","DOI":"10.1074\/jbc.M201151200","article-title":"Vitamin C prevents DNA mutation induced by oxidative stress","volume":"277","author":"E A Lutsenko","year":"2002","journal-title":"Journal of Biological Chemistry"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1080\/10408690490464960","article-title":"Comprehensive study on vitamin C equivalent antioxidant capacity (VCEAC) of\n                    various polyphenolics in scavenging a free radical and its structural\n                    relationship","volume":"44","author":"D-O Kim","year":"2004","journal-title":"Critical reviews in food science and nutrition"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"109891","DOI":"10.1016\/j.intimp.2023.109891","article-title":"Combination of metformin and hesperidin mitigates cyclophosphamide-induced\n                    hepatotoxicity. Emerging role of PPAR-\u03b3\/Nrf-2\/NF-\u03baB signaling pathway","volume":"117","author":"K M El-Beheiry","year":"2023","journal-title":"International Immunopharmacology"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"109368","DOI":"10.1016\/j.cbi.2021.109368","article-title":"Activation of autophagy and suppression of apoptosis by dapagliflozin attenuates\n                    experimental inflammatory bowel disease in rats: Targeting AMPK\/mTOR, HMGB1\/RAGE\n                    and Nrf2\/HO-1 pathways","volume":"335","author":"H H Arab","year":"2021","journal-title":"Chemico-biological interactions"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"213","DOI":"10.2147\/vhrm.2006.2.3.213","article-title":"Angiogenesis in cancer","volume":"2","author":"N Nishida","year":"2006","journal-title":"Vascular health and risk management"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s12933-017-0584-9","article-title":"Combined effect of metformin with ascorbic acid versus acetyl salicylic acid on\n                    diabetes-related cardiovascular complication; a 12-month single blind\n                    multicenter randomized control trial","volume":"16","author":"S W Gillani","year":"2017","journal-title":"Cardiovascular Diabetology"},{"key":"ref69","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.brainres.2017.08.019","article-title":"Metformin and ascorbic acid combination therapy ameliorates type 2 diabetes\n                    mellitus and comorbid depression in rats","volume":"1674","author":"N Shivavedi","year":"2017","journal-title":"Brain Research"}],"container-title":["Drug Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2317-7578.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T12:31:57Z","timestamp":1730809917000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2317-7578"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7]]},"references-count":67,"journal-issue":{"issue":"06","published-online":{"date-parts":[[2024,7,5]]},"published-print":{"date-parts":[[2024,7]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2317-7578","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["2194-9379","2194-9387"],"issn-type":[{"type":"print","value":"2194-9379"},{"type":"electronic","value":"2194-9387"}],"subject":[],"published":{"date-parts":[[2024,7]]}}}