Screening study of anti-emetics to improve GDF15-induced malaise and anorexia: Implications for emesis control.

Autor: Borner T; Department of Biobehavioral Health Sciences, University of Pennsylvania, School of Nursing, Philadelphia, PA 19104, United States; Department of Psychiatry, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, United States. Electronic address: titob@nursing.upenn.edu., Doebley SA; Department of Biobehavioral Health Sciences, University of Pennsylvania, School of Nursing, Philadelphia, PA 19104, United States., Furst CD; Department of Biobehavioral Health Sciences, University of Pennsylvania, School of Nursing, Philadelphia, PA 19104, United States., Pataro AM; Department of Biobehavioral Health Sciences, University of Pennsylvania, School of Nursing, Philadelphia, PA 19104, United States., Halas JG; Department of Biobehavioral Health Sciences, University of Pennsylvania, School of Nursing, Philadelphia, PA 19104, United States., Gao X; Department of Biobehavioral Health Sciences, University of Pennsylvania, School of Nursing, Philadelphia, PA 19104, United States., Choi GK; Department of Biobehavioral Health Sciences, University of Pennsylvania, School of Nursing, Philadelphia, PA 19104, United States., Ramadan SA; Department of Biobehavioral Health Sciences, University of Pennsylvania, School of Nursing, Philadelphia, PA 19104, United States., Chow A; Department of Biobehavioral Health Sciences, University of Pennsylvania, School of Nursing, Philadelphia, PA 19104, United States., De Jonghe BC; Department of Biobehavioral Health Sciences, University of Pennsylvania, School of Nursing, Philadelphia, PA 19104, United States; Department of Psychiatry, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, United States.
Jazyk: angličtina
Zdroj: Physiology & behavior [Physiol Behav] 2023 Aug 01; Vol. 267, pp. 114229. Date of Electronic Publication: 2023 May 08.
DOI: 10.1016/j.physbeh.2023.114229
Abstrakt: Considerable preclinical and clinical attention has focused on the food intake and body weight suppressive effects of growth differentiation factor 15 (GDF15) and its elevated blood levels as a consequence of disease states and disease treatment therapeutics. We have previously reported that exogenous administration of GDF15 induces anorexia through nausea and emesis in multiple species. Importantly, GDF15 signaling as a meditator of chemotherapy-induced anorexia and emesis has recently been demonstrated in both murine and nonhuman primate models. The mechanism, however, by which GDF15 induces malaise and the utility of existing therapeutic targets to counteract its effects remain largely unknown. Using a dose of GDF15 that mimics stimulated levels following chemotherapy administration and reliably induces malaise, we sought to screen anti-emetics that represent distinct pharmacotherapeutic classes hypothesized to reduce GDF15-induced effects in rats. Strikingly, our results showed that none of the tested compounds were effective at preventing GDF15-induced malaise. These results illustrate the complexity of GDF15 signaling mechanism and may have important implications for medical conditions characterized by elevated GDF15 levels and incomplete symptom control, such as chemotherapy-induced nausea and vomiting.
Competing Interests: Declaration of Competing Interest BCDJ receives research funding from Eli Lilly that was not used in support of these studies. BCDJ are TB are owners of Cantius Therapeutics, LLC that pursues biological work related to the GDF15/GFRAL system. All other authors declare no competing interests.
(Copyright © 2023. Published by Elsevier Inc.)
Databáze: MEDLINE
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