Nitric oxide synthase inhibitor aminoguanidine potentiates iminodipropionitrile-induced neurotoxicity in rats

This investigation was undertaken to study the effect of nitric oxide synthase inhibitor, aminoguanidine on iminodipropionitrile (IDPN)-induced neurobehavioral and vestibular toxicity in rats. The dyskinetic syndrome was produced in male Wistar rats by i.p. injections of IDPN (100 mg/kg) for 6 days. Aminoguanidine was administered orally in the doses of 50, 150 and 300 mg/kg, 60 min before IDPN in three different groups. Control rats received vehicle only, whereas another group was treated with 300 mg/kg of aminoguanidine alone (without IDPN). Our results showed that aminoguanidine significantly and dose dependently exacerbated the incidence and intensity of IDPN-induced dyskinetic head movements. Aminoguanidine potentiated IDPN-induced loss of air righting reflex. The histopathological examination of inner ear showed aggravation of IDPN-induced degeneration of sensory hair cells in the crista ampullaris by aminoguanidine. These results suggest the role of nitric oxide in IDPN-induced neurobehavioral and vestibular toxicity. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved.