{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:15:24Z","timestamp":1780359324677,"version":"3.54.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2014,6,1]],"date-time":"2014-06-01T00:00:00Z","timestamp":1401580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>This study aimed to elucidate the effect of bupropion (BUP) on high-fat diet (HFD)-treated rats that is to say the action of BUP on diabetes and hyperlipidemia with its consequences on liver and endothelial function.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Male Wistar rats were fed HFD or normal chow for 15 weeks then given either BUP (50\u2009mg\/kg) or distilled water by gavage for 4 weeks. The effect of BUP on diabetes, hyperlipidemia, hepatic and vascular functions as well as tumour necrosis factor-alpha (TNF)-\u03b1 were assessed. The intima-media thickness of the aorta was evaluated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>BUP significantly decreased serum lipid, liver enzyme, homeostasis model assessment for insulin resistance (HOMA-IR), serum TNF-\u03b1 and the impaired glucose tolerance. Liver from rats with non-alcoholic steatohepatitis (NASH) demonstrated significant higher TNF-\u03b1 level, inflammatory cell infiltration, ballooning and steatosis which significantly ameliorated by BUP treatment. Neither intima\/media ratio nor vascular reactivity to acetylcholine is improved by BUP treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>NASH induced by a HFD was associated with hyperlipidemia, insulin resistance, endothelial dysfunction and increase in liver TNF-\u03b1. All of these may contribute to the pathogenesis of NASH. BUP has potential role in improving metabolic and hepatic function with negative vascular effect. Since BUP is a well-known antidepressant, it will be a candidate drug in treatment of depression in hepatic diseased or metabolic disturbed patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1111\/jphp.12213","type":"journal-article","created":{"date-parts":[[2014,1,29]],"date-time":"2014-01-29T09:55:59Z","timestamp":1390989359000},"page":"793-801","source":"Crossref","is-referenced-by-count":11,"title":["Bupropion effects on high-fat diet-induced steatohepatitis and endothelial dysfunction in rats: role of tumour necrosis factor-alpha"],"prefix":"10.1093","volume":"66","author":[{"given":"Mai","family":"Ahmed","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Ain Shams University , Cairo,","place":["Egypt"]},{"name":"Faculty of Medicine, Ain Shams University , Cairo,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesam M","family":"El-Bakly","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ain Shams University , Cairo,","place":["Egypt"]},{"name":"Faculty of Medicine, Ain Shams University , Cairo,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M","family":"Zaki","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Ain Shams University , Cairo,","place":["Egypt"]},{"name":"Department of Pathology, Ain Shams University , Cairo,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lobna F","family":"abd Alzez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ain Shams University , Cairo,","place":["Egypt"]},{"name":"Faculty of Medicine, Ain Shams University , Cairo,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osama","family":"El serafi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ain Shams University , Cairo,","place":["Egypt"]},{"name":"Faculty of Medicine, Ain Shams University , Cairo,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,6,1]]},"reference":[{"key":"2024103109163585000_jphp12213-cit-0001","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1111\/j.1440-1746.2004.03312.x","article-title":"Non-alcoholic steatohepatitis in type 2 diabetes mellitus","volume":"19","author":"Gupte","year":"2004","journal-title":"J Gastroenterol Hepatol"},{"key":"2024103109163585000_jphp12213-cit-0002","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1590\/S0004-28032012000100015","article-title":"Metabolic syndrome and risk factors for non-alcoholic fatty liver disease","volume":"49","author":"Souza","year":"2012","journal-title":"Arq Gastroenterol"},{"key":"2024103109163585000_jphp12213-cit-0003","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1053\/j.gastro.2005.04.014","article-title":"The natural history of nonalcoholic fatty liver disease: a population-based cohort study","volume":"129","author":"Adams","year":"2005","journal-title":"Gastroenterology"},{"key":"2024103109163585000_jphp12213-cit-0004","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1136\/gut.48.2.206","article-title":"The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxeamia, and tumor necrosis factor alpha in the pathogenesis of nonalcoholic steatohepatitis","volume":"48","author":"Wigg","year":"2001","journal-title":"Gut"},{"key":"2024103109163585000_jphp12213-cit-0005","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1056\/NEJM200011163432007","article-title":"Cytokines in alcoholic and nonalcoholic steatohepatitis","volume":"343","author":"Tilg","year":"2000","journal-title":"N Engl J Med"},{"key":"2024103109163585000_jphp12213-cit-0006","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1002\/hep.20280","article-title":"Beyond insulin resistance in NASH. TNF-\u03b1 or adiponectin?","volume":"40","author":"Hui","year":"2004","journal-title":"Hepatology"},{"key":"2024103109163585000_jphp12213-cit-0007","doi-asserted-by":"crossref","first-page":"S167","DOI":"10.1016\/S0013-7006(12)70095-7","article-title":"Bipolar disorders and somatic comorbidities: a focus on metabolic syndrome, diabetes and cardiovascular disease","volume":"38","author":"Chauvet-G\u00e9linier","year":"2012","journal-title":"Encephale"},{"key":"2024103109163585000_jphp12213-cit-0008","first-page":"395","article-title":"Bupropion: a review of its mechanism of antidepressant activity","volume":"56","author":"Ascher","year":"1995","journal-title":"J Clin Psychiatry"},{"key":"2024103109163585000_jphp12213-cit-0009","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1586\/14737175.6.9.1249","article-title":"Bupropion: pharmacology and therapeutic applications","volume":"6","author":"Foley","year":"2006","journal-title":"Expert Rev Neurother"},{"key":"2024103109163585000_jphp12213-cit-0010","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1586\/14737175.7.1.17","article-title":"Bupropion for weight reduction","volume":"7","author":"Gadde","year":"2007","journal-title":"Expert Rev Neurother"},{"key":"2024103109163585000_jphp12213-cit-0011","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1038\/sj.npp.1301526","article-title":"Catecholamine reuptake inhibition causes weight loss by increasing locomotor activity and thermogenesis","volume":"33","author":"Billes","year":"2008","journal-title":"Neuropsychopharmacology"},{"key":"2024103109163585000_jphp12213-cit-0012","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/j.intimp.2005.12.007","article-title":"A new chapter opens in anti-inflammatory treatments: the antidepressant bupropion lowers production of tumor necrosis factor-alpha and interferon-gamma in mice","volume":"6","author":"Brustolim","year":"2006","journal-title":"Int Immunopharmacol"},{"key":"2024103109163585000_jphp12213-cit-0013","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.ejphar.2012.11.010","article-title":"Effects of amylin and bupropion\/naltrexone on food intake and body weight are interactive in rodent models","volume":"698","author":"Clapper","year":"2013","journal-title":"Eur J Pharmacol"},{"key":"2024103109163585000_jphp12213-cit-0014","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1017\/S0954422409990187","article-title":"Functional foods for dyslipidaemia and cardiovascular risk prevention","volume":"22","author":"Sirtori","year":"2009","journal-title":"Nutr Res Rev"},{"key":"2024103109163585000_jphp12213-cit-0015","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1038\/oby.2011.18","article-title":"Cafeteria diet is a robust model of human metabolic syndrome with liver and adipose inflammation: comparison to high-fat diet","volume":"19","author":"Sampey","year":"2011","journal-title":"Obesity (Silver Spring)"},{"key":"2024103109163585000_jphp12213-cit-0016","first-page":"357","article-title":"Effect of pectin and cellulose on content of minerals in the femur of rats","volume":"59","author":"Krzysik","year":"2009","journal-title":"Pol J Food Nutr Sci"},{"key":"2024103109163585000_jphp12213-cit-0017","doi-asserted-by":"crossref","first-page":"E545","DOI":"10.1152\/ajpendo.00120.2002","article-title":"Diets enriched in sucrose or fat increase gluconeogenesis and G-6-Pase but not basal glucose production in rats","volume":"283","author":"Commerford","year":"2002","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2024103109163585000_jphp12213-cit-0018","first-page":"354","article-title":"Fatty acid composition of beef, pork, and poultry fresh cuts, and some of their processed products","volume":"48","author":"Araujo de Vizcarrondo","year":"1998","journal-title":"Arch Latinoam Nutr"},{"key":"2024103109163585000_jphp12213-cit-0019","first-page":"74","article-title":"Metabolic parameters of rats prone to display wild-running of the audiogenic crisis and fights induced by REM-sleep deprivation","volume":"3","author":"Moraes","year":"2010","journal-title":"Sleep Sci"},{"key":"2024103109163585000_jphp12213-cit-0020","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"2024103109163585000_jphp12213-cit-0021","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1124\/jpet.105.100149","article-title":"Sesamin metabolites induce an endothelial nitric oxide-dependent vasorelaxation through their antioxidative property-independent mechanisms: possible involvement of the metabolites in the antihypertensive effect of sesamin","volume":"318","author":"Nakano","year":"2006","journal-title":"J Pharmacol Exp Ther"},{"key":"2024103109163585000_jphp12213-cit-0022","first-page":"139","article-title":"Comparative histopathology of radial artery versus internal thoracic artery and risk factors of developments of internal hyperplasia and atherosclerosis","volume":"100","author":"Ruengsakulrac","year":"1999","journal-title":"Circulation"},{"key":"2024103109163585000_jphp12213-cit-0023","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1677\/jme.1.01909","article-title":"Defining high-fat-diet rat models: metabolic and molecular effects of different fat types","volume":"36","author":"Buettner","year":"2006","journal-title":"J Mol Endocrinol"},{"key":"2024103109163585000_jphp12213-cit-0024","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1016\/j.lfs.2006.03.021","article-title":"High-fat emulsion-induced rat model of non alcoholic steatohepatitis","volume":"79","author":"Zou","year":"2006","journal-title":"Life Sci"},{"key":"2024103109163585000_jphp12213-cit-0025","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1743-7075-4-4","article-title":"Long term highly saturated fat diet does not induce NASH in Wistar rats","volume":"4","author":"Romestaing","year":"2007","journal-title":"Nutr Metab"},{"key":"2024103109163585000_jphp12213-cit-0026","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1093\/ajcn\/79.3.502","article-title":"Model of nonalcoholic steatohepatitis","volume":"79","author":"Lieber","year":"2004","journal-title":"Am J Clin Nutr"},{"key":"2024103109163585000_jphp12213-cit-0027","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1007\/s10620-009-0815-3","article-title":"Characterization of high fat diet induced non-alcoholic steatohepatitis with fibrosis in rats","volume":"55","author":"Xu","year":"2010","journal-title":"Dig Dis Sci"},{"key":"2024103109163585000_jphp12213-cit-0028","first-page":"57","article-title":"Oxidative stress and enzymatic antioxidant status in patients with nonalcoholic steatohepatitis","volume":"34","author":"Koruk","year":"2004","journal-title":"Ann Clin Lab Sci"},{"key":"2024103109163585000_jphp12213-cit-0029","first-page":"614","article-title":"TNF-alpha induces hepatic steatosis in mice by enhancing gene expression of sterol regulatory element binding protein-1c (SREBP-1c)","volume":"232","author":"Endo","year":"2007","journal-title":"Exp Biol Med"},{"key":"2024103109163585000_jphp12213-cit-0030","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1053\/j.gastro.2005.09.004","article-title":"NF-kappaB activation, rather than TNF mediates hepatic inflammation in a murine dietary model of steatohepatitis","volume":"129","author":"Dela Pena","year":"2005","journal-title":"Gastroenterology"},{"key":"2024103109163585000_jphp12213-cit-0031","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.biochi.2004.10.019","article-title":"Positive and negative regulation of insulin signaling through IRS-1 phosphorylation","volume":"87","author":"Gual","year":"2005","journal-title":"Biochimie"},{"key":"2024103109163585000_jphp12213-cit-0032","doi-asserted-by":"crossref","first-page":"831","DOI":"10.2337\/diacare.23.6.831","article-title":"Polymorphism of the tumor necrosis factor-receptor 2 gene is associated with obesity, leptin levels, and insulin resistance in young subjects and diet\u2013treated type 2 diabetic patients","volume":"23","author":"Fernandez-Real","year":"2000","journal-title":"Diabetes Care"},{"key":"2024103109163585000_jphp12213-cit-0033","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.3109\/00365521.2010.497938","article-title":"A novel non-alcoholic steatohepatitis animal model featured with insulin resistance, hepatic inflammation and fibrosis","volume":"45","author":"Zhao","year":"2010","journal-title":"Scand J Gastroenterol"},{"key":"2024103109163585000_jphp12213-cit-0034","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/0891-5849(94)90040-X","article-title":"Free radical in diabetic endothelial cell dysfunction","volume":"16","author":"Tesfamariam","year":"1994","journal-title":"Free Radic Biol Med"},{"key":"2024103109163585000_jphp12213-cit-0035","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.2337\/diab.41.9.1076","article-title":"Impaired insulin-mediated skeletal muscle blood flow in patients with NIDDM","volume":"41","author":"Laakso","year":"1992","journal-title":"Diabetes"},{"key":"2024103109163585000_jphp12213-cit-0036","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1002\/dmrr.634","article-title":"Insulin resistance and endothelial dysfunc tion: the road map to cardiovascular diseases","volume":"22","author":"Cersosimo","year":"2006","journal-title":"Diabetes Metab Res Rev"},{"key":"2024103109163585000_jphp12213-cit-0037","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.jhep.2010.04.030","article-title":"Prevalence of non-alcoholic fatty liver disease and its association with cardiovascular disease in patients with type 1 diabetes","volume":"53","author":"Targher","year":"2010","journal-title":"Hepatology"},{"key":"2024103109163585000_jphp12213-cit-0038","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1161\/ATVBAHA.107.142521","article-title":"TNF-alpha contributes to endothelial dysfunction by upregulating arginase in ischemia\/reperfusion injury","volume":"27","author":"Gao","year":"2007","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2024103109163585000_jphp12213-cit-0039","first-page":"667","article-title":"Different effects of the antidepressant drugs imipramine, maprotiline and bupropion on insulin secretion from mouse pancreatic islets","volume":"46","author":"El-Dakhakhny","year":"1996","journal-title":"Arzneimittelforschung"},{"key":"2024103109163585000_jphp12213-cit-0040","first-page":"295","article-title":"Bupropion is a nicotinic antagonist","volume":"7","author":"Slemmer","year":"2000","journal-title":"J Pharmacol Exp Ther"}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjphp.12213","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjphp.12213","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/66\/6\/793\/60252751\/jphp12213.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/66\/6\/793\/60252751\/jphp12213.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T09:24:20Z","timestamp":1730366660000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/66\/6\/793\/6128116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,6,1]]},"references-count":40,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2014,6,1]]},"published-print":{"date-parts":[[2014,6,1]]}},"URL":"https:\/\/doi.org\/10.1111\/jphp.12213","relation":{},"ISSN":["0022-3573","2042-7158"],"issn-type":[{"value":"0022-3573","type":"print"},{"value":"2042-7158","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2014,6]]},"published":{"date-parts":[[2014,6,1]]}}}