On the neurotoxicity of systemically administered putrescine: influence of kinetic factors

Putrescine (PUT) given ip to male rats produced a dose-dependent behavioural response. The observed signs were mainly shaking behaviour and motor disorders. The severity of the motor signs closely correlated with cortical PUT levels. After [14C]-PUT, the levels of related radioactivity ([14C]-PUTrr) in frontal cortex paralleled the levels of tracer in blood. Furthermore, the levels of tracer in blood and in frontal cortex were higher in the animals with toxicity signs than in non-affected ones. The frontal cortex levels of polyamines determined by HPLC revealed that only PUT paralleled the severity of the clinical status of the rats. No modifications of spermidine (SD) or spermine (SM) content were detected. Two hours after [14C]-PUT administration, only about 30% of the cortical [14C]-PUTrr was analyzed as PUT itself and no radioactivity was detected as SD and SM. Our results suggest that the radioactivity not associated to PUT could be related to more polar metabolites than SD or SM as acetylated derivatives.