The flavonoid baicalin protects against cerebrovascular dysfunction and brain inflammation in experimental heatstroke.
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.
Chang
Ching-Ping
CP
Department of Biotechnology, Southern Taiwan University of Technology, Tainan Hsien, Taiwan 710.
Huang
Wu-Tein
WT
Cheng
Bor-Chih
BC
Hsu
Chuan-Chih
CC
Lin
Mao-Tsun
MT
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002396:Catechols / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005419:Flavonoids / Q000627:therapeutic use*; D018698:Glutamic Acid / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D018883:Heat Stroke / Q000150:complications; D062385:Hydroxybenzoates; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D019586:Intracranial Hypertension / Q000209:etiology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002396:Catechols; D016207:Cytokines; D005419:Flavonoids; D062385:Hydroxybenzoates; C038044:baicalin; D018698:Glutamic Acid; C009135:2,3-dihydroxybenzoic acid; D005990:Glycerol