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: Chia-Yu Chang, Jen-Yin Chen, Sheng-Hsien Chen, Tain-Junn Cheng, Mao-Tsun Lin, Miao-Lin Hu
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 93 Pg. 84-93 (Apr 2016) ISSN: 1873-4596 [Electronic] United States
• PMID: 26703968 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016. Published by Elsevier Inc.

Chemical References

• Ascorbic Acid

Topics

• Animals
• Ascorbic Acid (administration & dosage)
• Death
• Heat Stroke (drug therapy, pathology)
• Humans
• Hypothalamus (drug effects, pathology)
• Inflammation (drug therapy, pathology)
• Mice
• Neurons (drug effects, pathology)
• Sepsis (drug therapy, pathology)