Ghrelin as a Novel Therapy for Radiation Combined Injury

Abstract

The threat of nuclear terrorism has led to growing worldwide concern about exposure to radiation. Acute radiation syndrome, or radiation sickness, develops after whole-body or a partial-body irradiation with a high dose of radiation. In the terrorist radiation exposure scenario, however, radiation victims likely suffer from additional injuries such as trauma, burns, wounds or sepsis. Thus, high-dose radiation injuries and appropriate therapeutic interventions must be studied. Despite advances in our understanding of the pathophysiology of radiation injury, very little information is available on the therapeutic approaches to radiation combined injury. In this review, we describe briefly the pathological consequences of ionizing radiation and provide an overview of the animal models of radiation combined injury. We highlight the combined radiation and sepsis model we recently established and suggest the use of ghrelin, a novel gastrointestinal hormone, as a potential therapy for radiation combined injury.

Combined Therapy of Pegylated G-CSF and Alxn4100TPO Improves Survival and Mitigates Acute Radiation Syndrome after Whole-Body Ionizing Irradiation Alone and Followed by Wound Trauma

“…These results are consistent with previously reported observations in rats (40, 41), guinea pigs (42), dogs (43), swine (44) and mice (1, 5, 6, 45–48). Consequences of either radiation alone or combined injury include acute myelosuppression, thrombocytopenia, immune system inhibition, fluid imbalance, macro/microcirculation failure, massive cellular damage and disruption of vital organ functions, which lead to multiple organ dysfunction syndrome and multiple organ failure, the most frequent causes of death after irradiation (42–44).…”

“…In contrast to the mice subjected to radiation alone, peg-G-CSF failed to improve survival after combined injury with burn. This could be due to the complexity of mechanisms of combined injuries, involving the enhancement of serum cytokines/chemokines and systemic bacterial infection (7, 47, 48), which requires more than peg-G-CSF to manage the imbalance of homeostasis. The G-CSF survival improvement after irradiation alone in our study is consistent with that observed in nonhuman primates (8, 20).…”

Thrombopoietin Receptor Agonist Mitigates Hematopoietic Radiation Syndrome and Improves Survival after Whole-Body Ionizing Irradiation Followed by Wound Trauma

“…Radiation delayed wound-healing abilities. These results are consistent with previous observations in rats [20, 21], guinea pigs [22], dogs [23], swine [24], and mice [1, 5, 6, 15, 25–27]. Medical sequelae of either RI or CI include acute myelosuppression, immune system inhibition, fluid imbalance, systemic inflammation, macro-/microcirculation failure, massive cellular damage, sepsis, and disruption of vital organ functions, which lead to MOD and MOF, the most frequent causes of death after irradiation [22–24].…”

Ghrelin and fibrogenesis: Relief for a hungry liver

“…An important feature of animals treated with ghrelin was the lower degree of hepatocellular injury, highlighted by dedicated experiments using an acute toxic model of liver injury. The ability of ghrelin to counteract tissue damage is in line with the protective roles reported in other tissues [7,8]. In the liver, ghrelin affected several components of tissue injury, namely inflammation, apoptosis, and generation of oxidative stressrelated molecules (Fig.…”