Ghrelin Peptide Boosts Survival and Vascular Health After Radiation Exposure

Exposure to Total Body Irradiation (TBI), whether from accidental events or medical treatments like bone marrow transplantation, causes severe damage to multiple organ systems. A critical component of this damage is the disruption of vascular integrity, leading to increased permeability, hemorrhage, and systemic inflammation, which significantly contributes to morbidity and mortality. Despite the severe consequences, there are currently limited effective therapeutic strategies to mitigate the acute vascular injury induced by TBI. This study addresses the urgent need for novel interventions to protect the vasculature and improve outcomes following TBI, specifically by investigating the potential of human ghrelin.

Treatment with human ghrelin significantly improved survival and preserved vascular integrity in irradiated mice. The 30-day survival rate in the ghrelin-treated group was 60%, a substantial increase compared to the 15% survival rate observed in the saline-treated control group (p<0.001). Vascular permeability, a key indicator of damage, was markedly reduced; Evans Blue extravasation in the lungs and small intestine was decreased by 55% and 48%, respectively, in ghrelin-treated animals compared to controls (p<0.01). Furthermore, ghrelin treatment maintained endothelial barrier function, evidenced by a 2.8-fold increase in tight junction protein ZO-1 expression and a 2.1-fold increase in VE-cadherin in endothelial cells. Systemic inflammation was also attenuated, with plasma levels of IL-6 and TNF-α being 70% and 65% lower, respectively, in the ghrelin group at 72 hours post-irradiation. The most critical finding was that human ghrelin treatment led to a 4-fold increase in 30-day survival following lethal total body irradiation, demonstrating its potent radioprotective effects.