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Exploring the role of ghrelin and des-acyl ghrelin in chemotherapy-induced nausea and vomiting.
Yang, Lingqing; Kung, Charmaine J S; Lu, Zengbing; Liu, Julia Y H; Ngan, Man Piu; Sakai, Takafumi; Sakata, Ichiro; Chan, Sze Wa; Tu, Longlong; Rudd, John A.
Afiliación
  • Yang L; Emesis Research Group, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
  • Kung CJS; Emesis Research Group, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
  • Lu Z; Emesis Research Group, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
  • Liu JYH; Emesis Research Group, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
  • Ngan MP; Emesis Research Group, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
  • Sakai T; Faculty of Science, Graduate School of Science and Engineering, Saitama University, Shimo-Okubo 255, Sakura-ku, Saitama-shi, 338-8570, Japan.
  • Sakata I; Faculty of Science, Graduate School of Science and Engineering, Saitama University, Shimo-Okubo 255, Sakura-ku, Saitama-shi, 338-8570, Japan.
  • Chan SW; School of Health Sciences, Saint Francis University, Tseung Kwan O, New Territories, Hong Kong.
  • Tu L; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, USA.
  • Rudd JA; Emesis Research Group, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong. Electronic address: jar@cuhk.edu.hk.
Neuropharmacology ; 251: 109919, 2024 Jun 15.
Article en En | MEDLINE | ID: mdl-38548221
ABSTRACT
Ghrelin and its mimetics have been shown to reduce cisplatin-induced emesis in preclinical studies using ferrets and shrews. This study investigated the effectiveness of ghrelin and des-acyl ghrelin (DAG) in antagonizing cisplatin-induced emesis and physiological changes indicative of nausea in Suncus murinus. Animals implanted with radiotelemetry devices were administered ghrelin (0.2, 1.0, and 5.0 µg/day), DAG (0.2, 1.0, and 5.0 µg/day), or saline (14 µL/day) intracerebroventricularly 4 days before and 3 days after treatment with cisplatin (30 mg/kg). At the end, the anti-apoptotic potentials of ghrelin and DAG were assessed by measuring Bax expression and cytochrome C activity. Neurotransmitter changes in the brain were evaluated using liquid chromatography-mass spectrometry analysis. Ghrelin and DAG reduced cisplatin-induced emesis in the delayed (24-72 h) but not the acute phase (0-24 h) of emesis. Ghrelin also partially reversed the inhibitory effects of cisplatin on food intake without affecting gastrointestinal myoelectrical activity or causing hypothermia; however, ghrelin or DAG did not prevent these effects. Ghrelin and DAG could attenuate the cisplatin-induced upregulation of Bax and cytochrome C in the ileum. Cisplatin dysregulated neurotransmitter levels in the frontal cortex, amygdala, thalamus, hypothalamus, and brainstem, and this was partially restored by low doses of ghrelin and DAG. Our findings suggest that ghrelin and DAG exhibit protective effects against cisplatin-induced delayed emesis. The underlying antiemetic mechanism may involve GHSR and/or unspecified pathways that modulate the neurotransmitters involved in emesis control in the brain and an action to attenuate apoptosis in the gastrointestinal tract.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antieméticos / Antineoplásicos Límite: Animals Idioma: En Revista: Neuropharmacology Año: 2024 Tipo del documento: Article País de afiliación: Hong Kong Pais de publicación: Reino Unido
Texto completo
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Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antieméticos / Antineoplásicos Límite: Animals Idioma: En Revista: Neuropharmacology Año: 2024 Tipo del documento: Article País de afiliación: Hong Kong Pais de publicación: Reino Unido