The present study was performed to assess the prophylactic effect of
baicalin, a
flavonoid compound, in an animal model of
heatstroke. Anesthetized rats, immediately before the start of heat stress, were divided into two major groups and given the following: vehicle
solution (1mL per kg
body weight) or
baicalin (10-40mg per kg
body weight) intravenously. They were exposed to ambient temperature of 43 degrees C to induce
heatstroke. Another group of rats was exposed to room temperature (24 degrees C) and used as normothermic controls. Their physiologic and biochemical parameters were continuously monitored. When the vehicle-pretreated rats underwent heat stress, their survival time values were found to be 20-28min. Pretreatment with intravenous doses of
baicalin significantly improved survival during
heatstroke (65-248min). As compared to those of normothermic controls, all vehicle-pretreated
heatstroke animals displayed higher levels of core temperature, intracranial pressure, and
nitric oxide metabolite (NO(2)(-)),
glutamate,
glycerol,
lactate/
pyruvate ratio, and
dihydroxybenzoic acid (DHBA) in hypothalamus. In addition, both serum and hypothalamic levels of
interleukin-1beta (IL-1beta) and
tumor necrosis factor-alpha (
TNF-alpha) as well as plasma levels of
creatinine, serum
urea nitrogen,
glutamic oxaloacetic transaminase,
glutamic pyruvic transaminase and
alkaline phosphatase were elevated after
heatstroke onset. In contrast, all vehicle-pretreated
heatstroke animals had lower levels of mean arterial pressure, cerebral perfusion pressure, cerebral blood flow, and brain PO(2). Administration of
baicalin before the start of heat exposure significantly reduced the
hyperthermia,
intracranial hypertension, and the increased levels of NO(2)(-),
glutamate,
glycerol,
lactate/
pyruvate ratio, and DHBA in the hypothalamus that occurred during
heatstroke. The
heatstroke-induced increased levels of IL-1beta and
TNF-alpha in both the serum and hypothalamus, and renal and hepatic dysfunction were suppressed by
baicalin pretreatment. In contrast, both the serum and hypothalamic levels of
IL-10 were significantly elevated by
baicalin during
heatstroke. We successfully demonstrated that
baicalin can be used as a prophylactic agent for
heatstroke. In particular,
baicalin may protect against cerebrovascular dysfunction and
brain inflammation in
heatstroke.