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 1h) 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 2.5h post-WBH.
Heatstroke mice were subcutaneously treated with
flutamide (12.5-50mg/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.