Flutamide,  an androgen receptor antagonist, improves heatstroke outcomes in mice

doi:10.1016/j.ejphar.2012.05.002

Chia Nan University of Pharmacy & Science Institutional Repository > 環境永續暨休閒學院 > 休閒保健管理系(所) > 期刊論文 > Item 310902800/27590

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標題:	Flutamide, an androgen receptor antagonist, improves heatstroke outcomes in mice
作者:	Lin, Chian-Yuh Hsu, Chuan-Chih Lin, Mao-Tsun Chen, Sheng-Hsien
貢獻者:	休閒保健管理系
日期:	2012-08-05
上傳時間:	2014-03-21 16:14:31 (UTC+8)
摘要:	Flutamide has been used as an adjunct for decreasing the mortality from subsequent sepsis. Heatstroke resembles septic shock in many aspects. We hypothesized that heat-induced multiple organ dysfunction syndromes and lethality could be reduced by flutamide therapy. In heatstroke groups, mice were exposed to whole body heating (41.2 degrees C, for 1 h) in a controlled-environment chamber. The heat-stressed mice were returned to normal room temperature (24 degrees C) after whole body heating. Mice still alive on day 4 of WBH treatment were considered survivors. Physiological and biochemical parameters were monitored for 2.5 h post-WBH. Heatstroke mice were subcutaneously treated with flutamide (12.5-50 mg/kg body weight in 0.05 ml) or vehicle solution (0.05 ml/kg body weight) once daily for 3 consecutive days post-WBH. We evaluated the effect of flutamide in heatstroke mice and showed that flutamide significantly (i) attenuated hypothermia, (ii) reduced the number of apoptotic cells in the hypothalamus, the spleen, the liver, and the kidney, (iii) attenuated the plasma index of toxic oxidizing radicals (e.g., nitric oxide metabolites and hydroxyl radicals), (iv) diminished the plasma index of the organ injury index (e.g., lactate dehydrogenase), (v) attenuated plasma systemic inflammation response molecules (e.g., tumor necrosis factor-a and interleukin-6), (vi) reduced the index of infiltration of polymorphonuclear neutrophils in the lung (e.g., myeloperoxidase activity), and (vii) allowed three times the fractional survival compared with vehicle. Thus, flutamide appears to be a novel agent for the treatment of mice with heatstroke or patients in the early stage of heatstroke. (C) 2012 Elsevier B.V. All rights reserved.
關聯:	European Journal of Pharmacology v.688 n.1-3 pp.62-67
显示于类别:	[休閒保健管理系(所)] 期刊論文

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