Heme Oxygenase-1 is involved in the protective effect of 17-DMAG in heat stroke rats
Ching-Wen Kunga Yi-Li Wangb Yen-Mei Leec
Abstract
Heat stroke is a life-threatening illness characterized by an elevated core body temperature that rises above 40℃ and central nervous system dysfunction that results in delirium, convulsions, or coma. Despite adequate lowering of the body temperature and aggressive support treatment, the mortality of heat stroke is still high. Thus, the aim of the present study is to evaluate whether 17-dimethylaminoethylamino-17- demethoxygeldanamycin (17-DMAG), a heat shock protein (HSP) 90 inhibitor, improves hemodynamic changes, and hepatic dysfunctions in heat stroke. Male Sprague-Dawley rats (280-350 g) exposed to heat as a model of heat stroke. The right femoral artery and vein of rats, under urethane (1.4 g/kg, ip) anesthesia, were cannulated with polyethylene tubing (PE 50). Two groups of animals were studied; (1) Vehicle-treated heat stroke group (HS group): heat stroke was induced by putting the rats into a chamber at 42℃. It is characterized when mean arterial blood pressure (MAP) dropped to a value of 25 mmHg from the peak level and Tco (core body temperature) elevated to about 42℃; (2) 17-DMAG + HS group: rats were pretreated with 17-DMAG (5 mg/kg, ip) 20 h before heat stroke. The values of MAP and heart rate of rats in HS group were significantly lower than those of 17-DMAG + HS group. 17-DMAG significantly prevented hypotension, and elevated plasma level of GPT induced by heat stroke. The expression of HO-1 in liver of 17-DMAG + HS group was significantly higher than that of HS group. In conclusion, 17-DMAG improves hemodynamics and hepatic function of heat stroke rats, which may be mediated by the increase of HO-1 induction.
Key Words: heat stroke; heat shock protein 90 inhibitor; 17-DMAG; HO-1
