Mild hypothermia protects against radiation-induced intestinal injury in mice via upregulation of heme oxygenase-1

Abstract

Radiation can cause life-threatening intestinal damage, whether intentional or unintentional. The present study investigated the effects of mild hypothermia on radiation-induced intestinal injury and survival. For 1 h before and after a lethal dose of whole-body irradiation (13 Gy), mice were either maintained at normothermia (37 °C) or exposed to mild hypothermia (32 °C). The survival of the mice was monitored for 30 days, and the morphological changes in the intestine and the cytokine levels in the serum of the irradiated mice at normothermia or hypothermia were assessed by histological examination at 12 h, 3.5 days, and 5 days after irradiation. Hypothermia delayed the death of the mice and attenuated the damage to the intestine. Hypothermia reduced apoptosis in the jejunum 12 h after irradiation exposure and restored crypt number, villi length, and epithelial length of the jejunum after 3.5 days. Mild hypothermia also reduced serum levels of proinflammatory cytokines after radiation exposure. Furthermore, heme oxygenase-1 (HO-1) was specifically upregulated in the mouse intestine by hypothermia. The HO-1 inhibitor Sn(IV) protoporphyrin IX dichloride partially reversed the effect mild hypothermia had on HO-1. These results suggest that hypothermia is a protective factor against radiation-induced intestinal damage and can, therefore, be effectively used as a radioprotective condition. In summary, mild hypothermia reduced cell death and inflammation in radiation-induced intestinal injury, partly through the regulation of HO-1.