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However, cisplatin\u2010induced dyspepsia syndromes, including delayed gastric emptying, gastric distension, early satiety, nausea, and vomiting, often force patients to take doses lower than those prescribed or even refuse treatment. D\u2010methionine has an appetite\u2010enhancing effect and alleviates weight loss during cisplatin treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This work established a model of anorexia and dyspepsia symptoms with intraperitoneal injection of cisplatin (5\u00a0mg\/kg) once a week for three cycles. Presupplementation with or without D\u2010methionine (300\u00a0mg\/kg) was performed. Orexigenic and anorexigenic hormones (ghrelin, leptin, and glucagon\u2010like peptide\u20101), tryptophan hydroxylase 1 (TPH1), 5\u2010hydroxytryptamine receptors (5\u2010HT<jats:sub>2C<\/jats:sub> and 5\u2010HT<jats:sub>3<\/jats:sub>), and hypothalamic feeding\u2010related peptides were measured by immunohistochemistry staining, enzyme\u2010linked immunosorbent assay, and real\u2010time PCR assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results<\/jats:title><jats:p>Cisplatin administration caused marked decrease in appetite and body weight, promoted adipose and fat tissue atrophy, and delayed gastric emptying and gastric distension, and D\u2010methionine preadministration prior to cisplatin administration significantly ameliorated these side effects. Besides, cisplatin induced an evident increase in serum ghrelin level, TPH1 activity, and 5\u2010HT<jats:sub>3<\/jats:sub> receptor expression in the intestine and decreased plasma leptin levels and gastric ghrelin mRNA gene expression levels. D\u2010methionine supplementation recovered these changes. The expression of orexigenic neuropeptide Y\/agouti\u2010related peptide and anorexigenic cocaine\u2010 and amphetamine\u2010regulated transcript proopiomelanocortin neurons were altered by D\u2010methionine supplementation in cisplatin\u2010induced anorexia rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and inferences<\/jats:title><jats:p>D\u2010methionine supplementation prevents cisplatin\u2010induced anorexia and dyspepsia syndrome possibly by attenuating intestinal tryptophan hydroxylase 1 activity and increasing plasma leptin concentration. Therefore, D\u2010methionine can be used as an adjuvant therapy for treating cisplatin\u2010induced adverse effects.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13803","type":"journal-article","created":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T07:23:18Z","timestamp":1580196198000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["D\u2010methionine improves cisplatin\u2010induced anorexia and dyspepsia syndrome by attenuating intestinal tryptophan hydroxylase 1 activity and increasing plasma leptin concentration"],"prefix":"10.1111","volume":"32","author":[{"given":"Yi\u2010Sin","family":"Wong","sequence":"first","affiliation":[{"name":"Department of Family Medicine Ditmanson Medical Foundation Chia\u2010Yi Christian Hospital Chiayi City Taiwan"},{"name":"Department of Food Science and Technology Chia Nan University of Pharmacy and Science Tainan 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