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.
Tariq
M
M
Neuroscience Research Group, Armed Forces Hospital, Riyadh, Saudi Arabia.
Khan
H A
HA
Al Deeb
S
S
Al Moutaery
K
K
D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004409:Dyskinesia, Drug-Induced; D020820:Dyskinesias / Q000453:epidemiology / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000473:pathology; D006257:Head / Q000503:physiopathology; D015994:Incidence; D008297:Male; D009068:Movement / Q000187:drug effects; D009498:Neurotoxins / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009570:Nitriles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects
D004791:Enzyme Inhibitors; D006146:Guanidines; D009498:Neurotoxins; D009570:Nitriles; C008110:3,3'-iminodipropionitrile; D019001:Nitric Oxide Synthase; C004479:pimagedine