Gordon Christopher J
Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, B105-04, US Environmental Protection Agency, 109 S.T.W. Alexander Drive, Research Triangle Park, NC 27711, USA.
Prog Brain Res. 2007;162:63-79. doi: 10.1016/S0079-6123(06)62005-0.
This chapter focuses on the effects of hyperthermia on drug and chemical toxicity. In general, hyperthermia exacerbates the toxicity of many types of drugs and environmental toxicants. Using rodents to model the potential responses of humans to hyperthermic drugs is hampered by the unique differences in thermoregulatory ability and body mass. Because of their relatively large surface area:mass ratio, ambient temperature has a more profound influence on the potential hyperthermic effect of a drug in rodents. The relative increase in heat production (i.e., as a percentage of their basal metabolic rate) required to raise core temperature by 1 degrees C will increase with a decrease in body mass. The thermoregulatory response to methylenedioxymethamphetamine (MDMA) is used to illustrate the differences in thermoregulatory responses of rats and humans to a hyperthermic drug. Overall, the interaction between ambient temperature and drug-induced changes in body temperature is critical in the evaluation of hyperthermic-induced toxicity in rodent models.
本章重点关注高温对药物和化学物质毒性的影响。一般来说，高温会加剧多种药物和环境毒物的毒性。利用啮齿动物来模拟人类对高温药物的潜在反应，受到体温调节能力和体重的独特差异的阻碍。由于它们相对较大的表面积与质量比，环境温度对啮齿动物体内药物的潜在高温效应有更深远的影响。将核心体温升高1摄氏度所需的产热相对增加量（即占其基础代谢率的百分比）会随着体重的降低而增加。以对亚甲基二氧甲基苯丙胺（摇头丸）的体温调节反应为例，说明大鼠和人类对高温药物的体温调节反应差异。总体而言，在评估啮齿动物模型中高温诱导的毒性时，环境温度与药物引起的体温变化之间的相互作用至关重要。
