Abstract

Thermal injury initiates a systemic inflammatory response resulting (among others) in the formation of reactive oxygen species (ROS), which may contribute to DNA injury [1]. One possible way of ROS-induced injury involves the excessive activation of poly-(ADP-ribose) polymerase (PARP). The aim of this study was to investigate the effect of the water-soluble inhibitor of PARP, 5-aminoisoquinoline (5-AIQ) on the circulatory and multiple organ failure in rats with thermal injury.Male Wistar rats (300–350 g) were divided in three groups: Control, burn (B) and burn-treated (BT) with 5-AIQ (3 mg/kg i.p., 1 minute after burn and every 2 h). The rats in groups B and BT received a 60% total body surface area scald burn (70°C during 30 seconds) under general anaesthesia, which was maintained until the end of the experiment. Rats were sacrificed 6 h after the injury and blood samples were collected immediately before sacrifice. Determination of serum biochemical markers of liver injury (AST and ALT) and renal dysfunction (urea and creatinine) was done. Mean arterial blood pressure (MAP) was determined every 30 min. Burned animals shown a significant and progressive decrease in MAP towards the end of 6 h experiment, and this hypotension was unaffected by 5-AIQ. Burn induced a significant increase on the serum levels of AST, ALT, urea and creatinine. This multiple organ injury/dysfunction was significantly attenuated by 5-AIQ. Thus, administration of 5-AIQ immediately after a 60% scald burn attenuated the dysfunction and liver injury, but not the circulatory failure associated with severe burn injury.References: 1.Martin D, Lewington A, Hammerman M, Padanilam B: Inhibition of poly (ADP-ribose) polymerase attenuates ischemic renal injury in rats. Am J Physiol Regulatiry Integrative Comp Physiol, 2000; 279: 1834-40

Keywords: thermal injury, Burn, PARP, 5-aminoisoquinoline, Rat