EFFECT OF PROPENTOFYLLINE ON FREE-RADICAL GENERATION DURING CEREBRAL HYPOXIA IN THE NEWBORN PIGLET

The present study tests the hypothesis that propentofylline, an adenos ine re-uptake inhibitor, will reduce free radical generation during ce rebral hypoxia. Ten newborn piglets were pretreated with propentofylli ne (10 mg/kg), five of which were subjected to hypoxia, while the othe r five were maintained at normoxia. Five untreated control piglets und erwent the same conditions. Hypoxia was induced through a decrease in FiO(2) to 0.11 and documented biochemically by a decrease in ATP and p hosphocreatine levels. Free radical formation in the cortex was detect ed directly using electron spin resonance spectroscopy with a spin tra p technique. Results demonstrate that free radicals, corresponding to the alkoxyl radical, increased significantly following hypoxia, and th at this increase was inhibited by pretreatment with propentofylline. C onjugated dienes, a lipid peroxidation product, also increased followi ng hypoxia and were subsequently inhibited by propentofylline. The adm inistration of propentofylline also significantly limited the hypoxia- induced decrease in tissue levels of ATP and phosphocreatine. These da ta demonstrate that pretreatment with propentofylline decreased free r adical generation and lipid peroxidation as well as preserved high ene rgy phosphates during cerebral hypoxia. (C) 1998 IBRO. Published by El sevier Science Ltd.