A potential for granulocyte-colony stimulating factor for use as a prophylactic agent for heatstroke in rats

• Published in: European journal of pharmacology 2011-07, Vol.661 (1), p.109-117
• Main Authors: Yung, Ming-Chi, Hsu, Chuan-Chih, Kang, Chieh-Yi, Lin, Chia-Li, Chang, Shu-Ling, Wang, Jhi-Joung, Lin, Mao-Tsun, Chen, Pei-Jarn, Chen, Sheng-Hsien
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Biological and medical sciences; Bone Marrow Cells - pathology; Cell Count; Cytokine; Endothelial Cells - pathology; Fever - complications; Fever - drug therapy; Granulocyte Colony-Stimulating Factor - pharmacology; Granulocyte Colony-Stimulating Factor - therapeutic use; Granulocyte-colony stimulating factor; Heat stroke; Heat Stroke - complications; Heat Stroke - metabolism; Heat Stroke - pathology; Heat Stroke - prevention & control; Hepatocytes - drug effects; Hepatocytes - pathology; Humans; Hypotension - complications; Hypotension - drug therapy; Hypothalamus; Hypothalamus - pathology; Inflammation - metabolism; Kidney - drug effects; Kidney - pathology; Male; Medical sciences; Nerve Growth Factors - metabolism; Neurons - drug effects; Neurons - pathology; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Stem Cells - drug effects; Stem Cells - pathology; Survival Analysis; Time Factors; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2011.04.018

Heatstroke is a form of excessive hyperthermia associated with a systemic inflammatory response that leads to multi-organ dysfunction in which central nervous system disorders predominate. Herein we determined to ascertain whether heat-induced multi-organ dysfunction in rats could be attenuated by granulocyte-colony stimulating factor (G-CSF) preconditioning. Anesthetized rats were divided into 2 major groups and given vehicle solution (isotonic saline, 0.3 ml, subcutaneously) or G-CSF (50–200 μg/kg body weight in 0.3 ml normal saline, subcutaneously) daily and consecutively for 5 days before the start of thermal experiments. They were exposed to an ambient temperature of 43 °C for 68 min to induce heatstroke. G-CSF preconditioning significantly prolonged the survival time in heatstroke rats in a dose-related way (82–98 min vs 127–243 min). The non-preconditioning heatstroke animals showed hyperthermia, arterial hypotension, increased serum levels of systemic inflammatory response molecules, increased hypothalamic apoptotic cell numbers as well as neuronal damage scores, and increased serum levels of renal and hepatic dysfunction indicators. These heatstroke syndromes could be significantly reduced by G-CSF preconditioning. Thus our results revealed a potential for G-CSF used as a prophylactic agent for heatstroke in rats.