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.

JMV2894, a novel growth hormone secretagogue, accelerates body mass recovery in an experimental model of cachexia / Bresciani, Elena; Rizzi, Laura; Molteni, Laura; Ravelli, Monica; Liantonio, Antonella; Ben Haj Salah, Khoubaib; Fehrentz, Jean Alain; Martinez, Jean; Omeljaniuk, Robert J.; Biagini, Giuseppe; Locatelli, Vittorio; Torsello, Antonio. - In: ENDOCRINE. - ISSN 1355-008X. - ELETTRONICO. - 58:1(2017), pp. 106-114. [10.1007/s12020-016-1184-2]

JMV2894, a novel growth hormone secretagogue, accelerates body mass recovery in an experimental model of cachexia

BIAGINI, Giuseppe;
2017

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.
2017
28-nov-2016
58
1
106
114
JMV2894, a novel growth hormone secretagogue, accelerates body mass recovery in an experimental model of cachexia / Bresciani, Elena; Rizzi, Laura; Molteni, Laura; Ravelli, Monica; Liantonio, Antonella; Ben Haj Salah, Khoubaib; Fehrentz, Jean Alain; Martinez, Jean; Omeljaniuk, Robert J.; Biagini, Giuseppe; Locatelli, Vittorio; Torsello, Antonio. - In: ENDOCRINE. - ISSN 1355-008X. - ELETTRONICO. - 58:1(2017), pp. 106-114. [10.1007/s12020-016-1184-2]
Bresciani, Elena; Rizzi, Laura; Molteni, Laura; Ravelli, Monica; Liantonio, Antonella; Ben Haj Salah, Khoubaib; Fehrentz, Jean Alain; Martinez, Jean; ...espandi
File in questo prodotto:
File Dimensione Formato  
bresciani2016.pdf

Accesso riservato

Tipologia: Versione pubblicata dall'editore
Dimensione 1.05 MB
Formato Adobe PDF
1.05 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1145314
Citazioni
  • ???jsp.display-item.citation.pmc??? 11
  • Scopus 12
  • ???jsp.display-item.citation.isi??? 11
social impact