Geranylgeranylacetone preconditioning may attenuate heat-induced inflammation and multiorgan dysfunction in rats

Abstract

OBJECTIVES: 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. METHODS: 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. KEY FINDINGS: 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. CONCLUSIONS: Geranylgeranylacetone preconditioning attenuates heat-induced inflammation and multiorgan dysfunction in rats.