THE BEHAVIORAL SYNDROME CAUSED BY 3,3'-IMINODIPROPIONITRILE AND RELATED NITRILES IN THE RAT IS ASSOCIATED WITH DEGENERATION OF THE VESTIBULAR SENSORY HAIR-CELLS

被引：114

作者：

LLORENS, J ^{[1
]}

DEMEMES, D ^{[1
]}

SANS, A ^{[1
]}

机构：

[1] UNIV MONTPELLIER 2,NEUROPHYSIOL SENSORIELLE LAB,INSERM,U 254,F-34095 MONTPELLIER 5,FRANCE

来源：

TOXICOLOGY AND APPLIED PHARMACOLOGY | 1993年 / 123卷 / 02期

关键词：

D O I：

10.1006/taap.1993.1238

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Animals exposed to 3,3’-iminodipropionitrile (IDPN) or to several similar nitriles develop a permanent syndrome of behavioral abnormalities. The present work addressed the hypothesis that this syndrome is caused by a toxic effect of these nitriles on the peripheral vestibular system. Male Long-Evans rats were given acute doses of IDPN (0, 200, 400, 600, or 1000 mg/kg, ip) and assessed for a number of behaviors indicative of vestibular function at postdosing times ranging from 1 day to 9 weeks. The pathological effects of IDPN on the morphology of the vestibular sensory epithelia were studied by scanning electron microscopy at 1, 2, 4, and 21 days after exposure. The behavioral study revealed dose-dependent deficits in vestibular function after IDPN. Alterations in vestibular morphology occurred at the same doses of IDPN that induced behavioral changes (400-1000 mg/kg). The pathological alterations after IDPN consisted of degeneration of the vestibular sensory hair cells, and no hair cells remained in the vestibular receptors 3 weeks after the 1000 mg/kg dose. A good correlation was also found for the time-course characteristics of the behavioral and the morphopathological effects of IDPN. The vestibular sensory epithelia displayed a regional pattern of differential sensitivity to the toxic effect of IDPN. Both intraepithelial and interepithelial differences in sensitivity were found. Crotonitrile (250 mg/kg, ip), which induces the same behavioral syndrome, was found to induce also degeneration of the vestibular hair cells. We conclude that IDPN and the similar nitriles that cause the same behavioral abnormalities are toxic to the peripheral vestibular system. © 1994 Academic Press. All rights reserved.

引用

页码：199 / 210

页数：12

共 57 条

[1] Ahmed A.E., Trieff N.M., Aliphatic nitriles: Metabolism and toxicity, Progress in Drug Metabolism, 7, pp. 229-294, (1983)
[2] Aran J.M., Erre J.P., Guilhaume A., Aurousseau C., The comparative ototoxicities of gentamicin, tobramycin and dibekacin in the guinea pig, Acta Oto-Laryngol. Suppi, 390, pp. 1-30, (1982)
[3] Anniko M., Wersall J., Experimentally (Atoxil) induced ampullar degeneration and damage to the maculae utriculi, Acta Otolaryngol, 83, pp. 429-440, (1977)
[4] Baird R.A., Desmadryl G., Fernandez C., Goldberg J.M., The vestibular nerve of the chinchilla. II. Relation between afferent response properties and peripheral innervation patterns in the semicircular canals, J. Neurophysiol, 60, pp. 182-203, (1988)
[5] Cadet J.L., The iminodipropionitrile (IDPN)-induced dyskinetic syndrome: Behavioral and biochemical pharmacology, Neurosci. Biobehav. Rev, 13, pp. 39-45, (1989)
[6] Chou S.M., Hartmann H.A., Axonal lesions and waltzing syndrome after IDPN administration in rats. With a concept - “Axostasis, Acta Neuropathol, 3, pp. 428-450, (1964)
[7] Crofton K.M., Knight T., Auditory deficits and motor dysfunction following iminodipropionitrile administration in the rat, Neurotoxicol. Teratol, 13, pp. 575-581, (1991)
[8] Dechesne C., Mbiene J.P., Sans A., Postnatal development of vestibular receptor surfaces in the rat, Ada Otolaryngol, 101, pp. 11-18, (1986)
[9] Dechesne C.J., Thomasset M., Brehier A., Sans A., Calbin-din (CaBP 28 kDa) localization in the peripheral vestibular system of various vertebrates, Hear. Res, 33, pp. 273-278, (1988)
[10] Defanti D.R., Carrier R.N., Defeo J.J., Relative uniformity of locomotor activity of mice treated with J3, J3-iminodipropionitrile (IDPN), J Pharmacol. Sci, 54, pp. 1371-1372, (1965)

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