title: JMV2894, a novel growth hormone secretagogue, accelerates body mass recovery in an experimental model of cachexia.
abstract: Oncologic patients subjected to chemotherapy frequently present aphagia, malnutrition, and cachexia. The purpose of this study was to investigate whether selected growth hormone secretagogues including hexarelin, JMV2894 and JMV2951 could antagonize body weight loss and wasting induced by cisplatin administration in rats. The three growth hormone secretagogues behaved as full agonists of the growth hormone secretagogues receptor both in terms of ability to stimulate calcium mobilization in Chinese hamster ovary cells and stimulation of growth hormone release in neonatal rats. Adult rats were (i) treated with vehicle throughout (controls), or (ii) treated with cisplatin (days 1-3) and a growth hormone secretagogues or vehicle, (days 1-12). Body weight and food consumption were measured daily. Although all growth hormone secretagogues caused initial transient acute increases in food intake, the total amount of food eaten by controls and growth hormone secretagogues treated groups over the 12 experimental days was not significantly different. All groups pre-treated with cisplatin lost up to 5-10 % body weight in the first 4 days; they subsequently gained weight at a rate comparable with controls. Interestingly, rats which received JMV2894 demonstrated a faster gain in body weight than any other growth hormone secretagogues treated group and at the end of the protocol reached a weight similar to that of controls. JMV2894 did not stimulate perirenal and epididymal fat accumulation but reduced MuRF mRNA levels in skeletal muscles. In conclusion, our findings demonstrate that JMV2894 antagonizes cisplatin induced weight loss in rats and may prove useful in antagonizing cachexia associated with cancer and chemotherapy in humans.
authors.affiliation: Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Bresciani
authors.affiliation: Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Rizzi
authors.affiliation: Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Molteni
authors.affiliation: Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Ravelli
authors.affiliation: Department of Pharmacy - Drug Sciences, University of Bari, Bari, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Liantonio
authors.affiliation: Max Mousseron Institute of Biomolecules UMR5247, CNRS, University of Montpellier, ENSCM, Montpellier, France.
authors.forename: Khoubaib
authors.initials: K
authors.lastname: Ben Haj Salah
authors.affiliation: Max Mousseron Institute of Biomolecules UMR5247, CNRS, University of Montpellier, ENSCM, Montpellier, France.
authors.forename: Jean-Alain
authors.initials: JA
authors.lastname: Fehrentz
authors.affiliation: Max Mousseron Institute of Biomolecules UMR5247, CNRS, University of Montpellier, ENSCM, Montpellier, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Martinez
authors.affiliation: Department of Biology, Lakehead University, Thunder Bay, ON, P7B 5E1, Canada.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Omeljaniuk
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, Laboratory of Experimental Epileptology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Biagini
authors.affiliation: Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Locatelli
authors.affiliation: Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy. antonio.torsello@unimib.it.
authors.forename: Antonio
authors.identifier: http://orcid.org/0000-0003-4557-676X
authors.initials: A
authors.lastname: Torsello
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000970:Antineoplastic Agents; D001835:Body Weight / Q000187:drug effects; D016466:CHO Cells; D002100:Cachexia / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002945:Cisplatin; D006224:Cricetinae; D003412:Cricetulus; D004435:Eating / Q000187:drug effects; D013006:Growth Hormone / Q000097:blood*; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D054440:Receptors, Ghrelin / Q000819:agonists*; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use; D034081:Wasting Disease, Chronic / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; C000627874:JMV2894; D010880:Piperidines; D054440:Receptors, Ghrelin; D014230:Triazoles; D013006:Growth Hormone; D002945:Cisplatin; D002118:Calcium
keywords: Cachexia; Cisplatin; GHS; Hexarelin; JMV2984