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

Chian Yuh Lin, Chuan Chih Hsu, Mao Tsun Lin, Sheng Hsien Chen

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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°C, for 1 h) in a controlled-environment chamber. The heat-stressed mice were returned to normal room temperature (24 °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-α 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.

Original languageEnglish
Pages (from-to)62-67
Number of pages6
JournalEuropean Journal of Pharmacology
Volume688
Issue number1-3
DOIs
Publication statusPublished - Aug 5 2012

Fingerprint

Androgen Receptor Antagonists
Heat Stroke
Flutamide
Heating
Hot Temperature
Body Weight
Controlled Environment
Multiple Organ Failure
Neutrophil Infiltration
Poisons
Septic Shock
Hypothermia
L-Lactate Dehydrogenase
Hydroxyl Radical
Peroxidase
Hypothalamus
Survivors
Interleukin-6
Sepsis
Nitric Oxide

Keywords

  • Cytokines
  • Flutamide
  • Heat stroke
  • Multiple organ injury

ASJC Scopus subject areas

  • Pharmacology

Cite this

Flutamide, an androgen receptor antagonist, improves heatstroke outcomes in mice. / Lin, Chian Yuh; Hsu, Chuan Chih; Lin, Mao Tsun; Chen, Sheng Hsien.

In: European Journal of Pharmacology, Vol. 688, No. 1-3, 05.08.2012, p. 62-67.

Research output: Contribution to journalArticle

Lin, Chian Yuh ; Hsu, Chuan Chih ; Lin, Mao Tsun ; Chen, Sheng Hsien. / Flutamide, an androgen receptor antagonist, improves heatstroke outcomes in mice. In: European Journal of Pharmacology. 2012 ; Vol. 688, No. 1-3. pp. 62-67.
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