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

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-HT 2C and 5-HT 3 ), 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-HT 3 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 cisplatininduced anorexia rats. Conclusions and inferences: D-methionine supplementation prevents cisplatin-in-duced 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.

Administration of Lactobacillus reuteri Combined with Clostridium butyricum Attenuates Cisplatin-Induced Renal Damage by Gut Microbiota Reconstitution, Increasing Butyric Acid Production, and Suppressing Renal Inflammation

“…Patients with hepatic fibrosis had a higher abundance of the Escherichia-Shigella and Enterobacteriaceae families [ 58 ]. Additionally, CKD patients showed higher levels of Enterobacteriaceae but lower levels of Ruminococcaceae compared with the healthy individuals [ 59 ]. Consistent with previous research, our results showed that cisplatin disturbed the intestinal microbiota that exacerbated mucosal damage [ 1 ] and kidney damage [ 2 , 19 ] and induced Escherichia-Shigella as the dominant genera [ 60 ].…”

Effects of Ginger Intake on Chemotherapy-Induced Nausea and Vomiting: A Systematic Review of Randomized Clinical Trials

“…Chemotherapy may affect gastrointestinal motility, as well as that of neurotransmitters. It was reported that the delayed gastric emptying caused by chemotherapy may also be an important factor in explaining CINV [ 48 , 49 , 50 ]. The gingerols in ginger markedly improved delayed gastric emptying induced by cisplatin in a dose-dependent manner [ 42 ].…”

Meclizine and Metabotropic Glutamate Receptor Agonists Attenuate Severe Pain and Ca2+ Activity of Primary Sensory Neurons in Chemotherapy-Induced Peripheral Neuropathy

“…One of the most common side effects of platinum-based chemotherapeutic drugs is weight loss (44)(45)(46). There have been many mechanisms proposed for how cisplatin and other platinum-based chemotherapeutic drugs cause weight loss (69)(70)(71)(72)(73)(74)(75)(76). Meclizine reduced both cisplatin-induced hypersensitivity to mechanical pain and attenuated cisplatin-induced weight loss.…”