Department of Brain Protection and Plasticity, Institute of Basic Medical Sciences, Beijing, 100850, China.
J Pharm Pharmacol. 2010 Jan;62(1):99-105. doi: 10.1211/jpp.62.01.0011.
Geranylgeranylacetone, an acyclic isoprenoid, is a non-toxic inducer of heat shock protein (HSP)70. HSP70 overproduction is associated with heat tolerance in rats. This study aimed to investigate whether geranylgeranylacetone preconditioning of rats reduced heat-induced inflammation and multiple organ dysfunction.
Anaesthetised rats were given vehicle or geranylgeranylacetone (800 mg/kg) orally. After 48 h they were exposed to ambient temperature of 43 degrees C for 70 min to induce heatstroke. Another group of rats kept at room temperature were used as normothermic controls.
Vehicle-treated rats all succumbed to heat stress; their survival time was 25 +/- 4 min. Pretreatment with geranylgeranylacetone significantly increased survival time to 92 +/- 15 min. Compared with normothermic controls, all vehicle-treated heatstroke rats displayed hepatic and renal dysfunction (e.g. increased plasma levels of serum urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase) and active inflammation (e.g. increased plasma and brain levels of interleukin-1 beta, tumour necrosis factor-alpha and interleukin-6). These heat-stress response indicators were all significantly suppressed by geranylgeranylacetone pretreatment. In addition, the plasma and brain levels of interleukin-10 (an anti-inflammatory cytokine) and brain levels of HSP70 were significantly increased after geranylgeranylacetone preconditioning during heatstroke.
Geranylgeranylacetone preconditioning attenuates heat-induced inflammation and multiorgan dysfunction in rats.
香叶基丙酮是一种无环异戊二烯，是热休克蛋白（HSP）70 的无毒诱导剂。HSP70 的过度产生与大鼠的耐热性有关。本研究旨在探讨香叶基丙酮预处理大鼠是否能减轻热诱导的炎症和多器官功能障碍。
麻醉大鼠给予载体或香叶基丙酮（800mg/kg）口服。48 小时后，它们暴露于环境温度为 43°C 的环境中 70 分钟，以诱导中暑。另一组在室温下保持的大鼠作为正常体温对照。
载体处理的大鼠均死于热应激；它们的存活时间为 25 +/- 4 分钟。香叶基丙酮预处理显著增加了存活时间至 92 +/- 15 分钟。与正常体温对照相比，所有载体处理的中暑大鼠均显示肝功能和肾功能障碍（如血清尿素氮、肌酐、天门冬氨酸转氨酶、丙氨酸转氨酶和碱性磷酸酶的血浆水平升高）和活跃的炎症（如白细胞介素-1β、肿瘤坏死因子-α和白细胞介素-6 的血浆和脑水平升高）。这些热应激反应指标均被香叶基丙酮预处理显著抑制。此外，在中暑期间，香叶基丙酮预处理后，血浆和脑内白细胞介素-10（抗炎细胞因子）的水平和脑内 HSP70 的水平显著增加。
香叶基丙酮预处理可减轻大鼠热诱导的炎症和多器官功能障碍。
