INTRAHIPPOCAMPAL INJECTION OF PARAQUAT PRODUCES APOPTOTIC CELL-DEATH WHICH IS PREVENTED BY THE LAZAROID U74389G, IN RATS

Injection of paraquat, a redox-cycling compound, into the rat hippocam pus produces limbic seizures and hippocampal damage. Here we report th at a proportion of the neuronal cell death caused by the herbicide occ urs via an apoptotic mechanism which appears to be mediated by oxygen free radicals. Adult male Wistar rats (n=12) received a single dose of paraquat (25nmol/0.5 mu l; 0.5 mu l/min rate) and were sacrificed 24 h later. Paraquat caused DNA fragmentation, nuclear chromatin marginal ization and compaction in all hippocampal subsectors, 24 h after its i njection, as revealed by both the TUNEL procedure and hematoxylin eosi n staining of coronal brain tissue sections. Pre-treatment with the fr ee radical scavenger lazaroid U74389G (30 mg/kg given ip 30 min before hand) significantly reduced paraquat-induced apoptosis, but did not pr otect against non apoptotic neuronal cell loss caused by the herbicide .