The toxicity of IDPN on the vestibular system of the rat: new insights on its effects on behavior and neurofilament transport.
3,3'-Iminodipropionitrile (IDPN) causes a permanent syndrome of abnormalities in spontaneous behavior and a deficit in the axonal transport of neurofilaments (NF). Male Long-Evans rats were given IDPN (0, 200, 400, 600, or 1000 mg/kg, ip, in saline) and assessed for behaviors indicative of vestibular function at 1 week post-dosing. The morphology of the peripheral vestibular system in animals dosed with 0, 200, 400, 600, 800, or 1000 mg/kg of IDPN was assessed at 4 days post-dosing by light microscopy on semithin sections. Animals receiving 1000, 1500, or 2000 mg/kg of IDPN were assessed for morphological alterations in the vestibular ganglion at 8 days post-dosing. Behavioral data indicated a dose-dependent loss of vestibular function after IDPN, the vestibular deficits first appearing at the 400 mg/kg dose level. IDPN exposure was also observed to result in degeneration of the vestibular sensory hair cells. Degenerative changes were already found at the 400 mg/kg dose level, and were extensive after 1000 mg/kg. In the ganglion neurons, no effects were observed after 1000 mg/kg of IDPN, but perikaryal accumulations of NF were found after 1500 or 2000 mg/kg. In conclusion, the data showed that low doses of IDPN are toxic to the vestibular hair cells, and suggest a link between this action and the effects of the chemical on spontaneous behavior. In addition, doses of IDPN larger than those required for toxicity to the vestibular sensory cells, induced accumulations of NF in the myelinated cell bodies of the vestibular ganglion neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
Departament de Farmacologia i Toxicologia, CSIC, Barcelona, Spain.
J
J
Llorens
D
D
Demêmes
A
A
Sans
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001692:Biological Transport / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005724:Ganglia / Q000187:drug effects; D008297:Male; D016900:Neurofilament Proteins / Q000378:metabolism*; D009570:Nitriles / Q000633:toxicity*; D051381:Rats; D014722:Vestibule, Labyrinth / Q000187:drug effects* / Q000473:pathology / Q000502:physiology
D016900:Neurofilament Proteins; D009570:Nitriles; C008110:3,3'-iminodipropionitrile