D-methionine improves cisplatin-induced anorexia and dyspepsia syndrome by attenuating intestinal tryptophan hydroxylase 1 activity and increasing plasma leptin concentration

doi:10.1111/nmo.13803

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標題:	D-methionine improves cisplatin-induced anorexia and dyspepsia syndrome by attenuating intestinal tryptophan hydroxylase 1 activity and increasing plasma leptin concentration
作者:	Wong, Yi-Sin Lin, Meei-Yn Liu, Pei-Fen Ko, Jiunn-Liang Huang, Guan-Ting Tu, Dom-Gene Ou, Chu-Chyn
貢獻者:	Chia Yi Christian Hosp, Ditmanson Med Fdn, Dept Family Med Chia Nan Univ Pharm & Sci, Dept Food Sci & Technol Natl Chung Hsing Univ, Dept Food Sci & Biotechnol Chung Shan Med Univ Hosp, Dept Med Oncol & Chest Med Chung Shan Med Univ, Inst Med Chung Shan Med Univ Hosp, Dept Nutr Chia Yi Christian Hosp, Ditmanson Med Fdn, Dept Nucl Med Natl Chung Cheng Univ, Dept Biomed Sci Chung Shan Med Univ, Sch Nutr
關鍵字:	5-HT3 receptor anorexia cisplatin D-methionine dyspepsia syndrome
日期:	2020
上傳時間:	2022-11-18 11:25:21 (UTC+8)
出版者:	Wiley
摘要:	Background Cisplatin is a widely used antineoplastic drug. However, cisplatin-induced 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-methionine has an appetite-enhancing effect and alleviates weight loss during cisplatin treatment. Methods This work established a model of anorexia and dyspepsia symptoms with intraperitoneal injection of cisplatin (5 mg/kg) once a week for three cycles. Presupplementation with or without D-methionine (300 mg/kg) was performed. Orexigenic and anorexigenic hormones (ghrelin, leptin, and glucagon-like peptide-1), tryptophan hydroxylase 1 (TPH1), 5-hydroxytryptamine receptors (5-HT2C and 5-HT3), and hypothalamic feeding-related peptides were measured by immunohistochemistry staining, enzyme-linked immunosorbent assay, and real-time PCR assay. Key results 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-methionine preadministration prior to cisplatin administration significantly ameliorated these side effects. Besides, cisplatin induced an evident increase in serum ghrelin level, TPH1 activity, and 5-HT3 receptor expression in the intestine and decreased plasma leptin levels and gastric ghrelin mRNA gene expression levels. D-methionine supplementation recovered these changes. The expression of orexigenic neuropeptide Y/agouti-related peptide and anorexigenic cocaine- and amphetamine-regulated transcript proopiomelanocortin neurons were altered by D-methionine supplementation in cisplatin-induced anorexia rats. Conclusions and inferences D-methionine supplementation prevents cisplatin-induced anorexia and dyspepsia syndrome possibly by attenuating intestinal tryptophan hydroxylase 1 activity and increasing plasma leptin concentration. Therefore, D-methionine can be used as an adjuvant therapy for treating cisplatin-induced adverse effects.
關聯:	Neurogastroenterology and Motility, v.32, n.6, pp.13
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