The present study was performed to assess the prophylactic effect of
platonin, a cyanine photosensitizing
dye and an inhibitor of proinflammatory
cytokines, in an animal model of
heatstroke. Anesthetized rats were immediately divided into 2 major groups after the start of heat stress and administered either isotonic
sodium chloride solution (dose, 1 mL/kg of
body weight i.v.) or
platonin (dose, 12.5-50 microg/mL per kilogram of
body weight i.v.). They were exposed to ambient temperature of 43 degrees C to induce
heatstroke. Another group of rats were exposed to room temperature (26 degrees C) and used as normothermic controls. Their physiological and biochemical parameters were continuously monitored. When the isotonic
sodium chloride solution-pretreated rats underwent heat stress, their survival time values were found to be from 20 to 24 min. Pretreatment with intravenous doses of
platonin (12.5-50 microg/mL per kilogram of
body weight) immediately after the start of heat exposure significantly improved survival time during
heatstroke (duration, 63-185 min). As compared with normothermic controls, all vehicle-pretreated
heatstroke animals displayed higher levels of
creatinine, serum
urea nitrogen,
alkaline phosphatase,
aspartate aminotransferase,
alanine aminotransferase,
tumor necrosis factor alpha, prothrombin time, activated partial thromboplastin time and
D-dimer in the plasma, cellular
ischemia and injury markers in striatum, and intracranial pressure. In contrast, all vehicle-pretreated
heatstroke animals had lower levels of mean arterial pressure, cerebral perfusion pressure, cerebral blood flow, brain Po2, and platelet count and
protein C in the plasma. Immediately after the start of heat exposure, the previous administration of
platonin significantly improved survival time by reducing the systemic
inflammation, hypercoagulable state, and tissue
ischemia and damage during
heatstroke. The results demonstrate that
platonin is effective for attenuation of
heatstroke reactions.