Despite the great clinical significance of radiation-induced cardiac damage, experimental
investigation of its mechanisms is an unmet need in medicine. Beneficial effects of
growth hormone-releasing hormone (GHRH) agonists in regeneration of the heart have
been demonstrated. The aim of this study was the evaluation of the potential of modern
GHRH agonistic analogs in prevention of radiation damage in an in vitro cardiac myocyte-based
model. Cultures of cardiac myocytes isolated from newborn rats (NRVM) were exposed
to a radiation dose of 10Gy. The effects of the agonistic analogs, JI-34 and MR-356,
of human GHRH on cell viability, proliferation, their mechanism of action and the
protein expression of the GHRH/SV1 receptors were studied. JI-34 and MR-356, had no
effect on cell viability or proliferation in unirradiated cultures. However, in irradiated
cells JI-34 showed protective effects on cell viability at concentrations of 10 and
100nM, and MR-356 at 500nM; but no such protective effect was detected on cell proliferation.
Both agonistic analogs decreased radiation-induced ROS level and JI-34 interfered
with the activation of SAFE/RISK pathways. Using Western blot analysis, a 52kDa protein
isoform of GHRHR was detected in the samples in both irradiated and unirradiated cells.
Since GHRH agonistic analogs, JI-34 and MR-356 alleviated radiation-induced damage
of cardiac myocytes, they should be tested in vivo as potential protective agents
against radiogenic heart damage.