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

Endocrine, 2016, Pages: Ahead of Print

E. Bresciani, L. Rizzi, L. Molteni, M. Ravelli, A. Liantonio, K. Ben Haj Salah, J. A. Fehrentz, J. Martinez, R. J. Omeljaniuk, G. Biagini, V. Locatelli, A. Torsello

Abstract

Oncol. 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 wt. 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 wt. and food consumption were measured daily. Although all growth hormone secretagogues caused initial transient acute increases in food intake, the total amt. of food eaten by controls and growth hormone secretagogues treated groups over the 12 exptl. days was not significantly different. All groups pre-treated with cisplatin lost up to 5-10 % body wt. in the first 4 days; they subsequently gained wt. at a rate comparable with controls. Interestingly, rats which received JMV2894 demonstrated a faster gain in body wt. than any other growth hormone secretagogues treated group and at the end of the protocol reached a wt. 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 wt. loss in rats and may prove useful in antagonizing cachexia assocd. with cancer and chemotherapy in humans.

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