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

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/24682

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/24682

Title:	D-methionine improves cisplatin-induced anorexia and dyspepsia syndrome by attenuating intestinal tryptophan hydroxylase 1 activity and increasing plasma leptin concentration
Authors:	Wong, YS;Lin, MY;Liu, PF;Ko, JL;Huang, GT;Tu, DG;Ou, CC
Keywords:	5-HT3 receptor;anorexia;cisplatin;D-methionine;dyspepsia syndrome
Date:	2020
Issue Date:	2022-08-09T08:06:19Z (UTC)
Publisher:	WILEY
ISSN:	1350-1925
Abstract:	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.
URI:	http://dx.doi.org/10.1111/nmo.13803 https://www.webofscience.com/wos/woscc/full-record/WOS:000509513900001 https://ir.csmu.edu.tw:8080/handle/310902500/24682
Relation:	NEUROGASTROENTEROLOGY AND MOTILITY ,2020 ,v32 ,issue 6
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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