title: Therapeutic treatment with ascorbate rescues mice from heat stroke-induced death by attenuating systemic inflammatory response and hypothalamic neuronal damage.
abstract: The impact of ascorbate on oxidative stress-related diseases is moderate because of its limited oral bioavailability and rapid clearance. However, recent evidence of the clinical benefit of parenteral vitamin C administration has emerged, especially in critical care. Heatstroke is defined as a form of excessive hyperthermia associated with a systemic inflammatory response that results in multiple organ dysfunctions in which central nervous system disorders such as delirium, convulsions, and coma are predominant. The thermoregulatory, immune, coagulation and tissue injury responses of heatstroke closely resemble those observed during sepsis and are likely mediated by similar cellular mechanisms. This study was performed by using the characteristic high lethality rate and sepsis-mimic systemic inflammatory response of a murine model of heat stroke to test our hypothesis that supra-physiological doses of ascorbate may have therapeutic use in critical care. We demonstrated that parenteral administration of ascorbate abrogated the lethality and thermoregulatory dysfunction in murine model of heat stroke by attenuating heat stroke-induced accelerated systemic inflammatory, coagulation responses and the resultant multiple organ injury, especially in hypothalamus. Overall, our findings support the hypothesis and notion that supra-physiological doses of ascorbate may have therapeutic use in critical care.
authors.affiliation: Department of Neurology, Chi Mei Medical Center, 901 Chung-Hwa Road, Yong kang, Tainan, Taiwan; Department of Food Science and Applied Biotechnology, National Chung-Hsing University, 250 Kuo-Kuang Road, Taichung 402, Taiwan; Center for General Education, Southern Taiwan University of Science and Technology, 1 Nan-Tai Street, Yong kang, Tainan, Taiwan.
authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Chang
authors.affiliation: Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan.
authors.forename: Jen-Yin
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Da-An Women and Children Hospital, Tainan, Taiwan.
authors.forename: Sheng-Hsien
authors.initials: SH
authors.lastname: Chen
authors.affiliation: Department of Neurology, Chi Mei Medical Center, 901 Chung-Hwa Road, Yong kang, Tainan, Taiwan; Department of the Senior Citizen Service Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
authors.forename: Tain-Junn
authors.initials: TJ
authors.lastname: Cheng
authors.affiliation: Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan.
authors.forename: Mao-Tsun
authors.initials: MT
authors.lastname: Lin
authors.affiliation: Department of Food Science and Applied Biotechnology, National Chung-Hsing University, 250 Kuo-Kuang Road, Taichung 402, Taiwan. Electronic address: mlhuhu@nchu.edu.tw.
authors.forename: Miao-Lin
authors.initials: ML
authors.lastname: Hu
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage*; D003643:Death; D018883:Heat Stroke / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018805:Sepsis / Q000188:drug therapy* / Q000473:pathology
chemical_list: D001205:Ascorbic Acid
keywords: Ascorbate; Heat stroke; Systemic inflammatory response