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Strain and Sex Differences in the Vestibular and Systemic Toxicity of 3,3’ -Iminodipropionitrile in Mice

The nitrile 3,3′-iminodipropionitrile (IDPN) causes a loss of hair cells in the vestibular epithelium of the inner ear in several species of both mammals and nonmammals. It is of interest as a model compound in ototoxicity and vestibular regeneration research, but its effects on the mouse, including the potential relevance of strain and sex differences for susceptibility, have not yet been thoroughly characterized. In this study, we compared the vestibular toxicity of IDPN in dose–response studies (0, 8, 12, 16, and 24 mmol/kg IDPN p.o.) in males and females of 2 different mouse strains (RjOrl:Swiss/CD-1 and 129S1/SvImJ). 3,3′-Iminodipropionitrile caused a dose-dependent loss of vestibular function in all sex and strain groups, as assessed by a specific battery of behavioral tests. However, large differences in systemic toxicity were recorded, with high systemic toxicity in 129S1 mice of both sexes compared to limited effects on the Swiss mice. Both male and female Swiss mice showed a marked increase of hindlimb stride width after exposure. The Swiss, but not the 129S1, mice treated with IDPN showed hyperactivity in the open field. The dose–response relationships in the behavioral effects were matched by the extent of hair cell loss assessed by scanning electron microscopy. Altogether, the data demonstrated prominent strain-dependent differences in the systemic toxicity of IDPN between 129S1 and Swiss mice, in contrast to no differences between the strains and small differences between the sexes in its vestibular toxicity. These results support the use of Swiss mice exposed to IDPN as a mouse lesion model for research in vestibular therapy and regeneration

This work was supported by the Spanish Ministry of Economy and Competitiveness (MINECO)—FEDER (grant numbers BFU2012-31164 and BFU2015-66109-R) and the Generalitat of Catalonia (grant number 2014 SGR 943)

info:eu-repo/grantAgreement/MINECO//BFU2012-31164/ES/DAÑO Y REPARACION VESTIBULAR EN LA OTOTOXICIDAD CRONICA: ETAPAS CELULARES, DEFICITS FISIOLOGICOS Y MECANISMOS MOLECULARES/

Oxford University Press (OUP)

Director: Ministerio de Economía y Competitividad (Espanya)
Autor: Boadas i Vaello, Pere
Sedó Cabezón, Lara
Verdú Navarro, Enrique
Llorens Baucells, Jordi
Data: 24 desembre 2016
Resum: The nitrile 3,3′-iminodipropionitrile (IDPN) causes a loss of hair cells in the vestibular epithelium of the inner ear in several species of both mammals and nonmammals. It is of interest as a model compound in ototoxicity and vestibular regeneration research, but its effects on the mouse, including the potential relevance of strain and sex differences for susceptibility, have not yet been thoroughly characterized. In this study, we compared the vestibular toxicity of IDPN in dose–response studies (0, 8, 12, 16, and 24 mmol/kg IDPN p.o.) in males and females of 2 different mouse strains (RjOrl:Swiss/CD-1 and 129S1/SvImJ). 3,3′-Iminodipropionitrile caused a dose-dependent loss of vestibular function in all sex and strain groups, as assessed by a specific battery of behavioral tests. However, large differences in systemic toxicity were recorded, with high systemic toxicity in 129S1 mice of both sexes compared to limited effects on the Swiss mice. Both male and female Swiss mice showed a marked increase of hindlimb stride width after exposure. The Swiss, but not the 129S1, mice treated with IDPN showed hyperactivity in the open field. The dose–response relationships in the behavioral effects were matched by the extent of hair cell loss assessed by scanning electron microscopy. Altogether, the data demonstrated prominent strain-dependent differences in the systemic toxicity of IDPN between 129S1 and Swiss mice, in contrast to no differences between the strains and small differences between the sexes in its vestibular toxicity. These results support the use of Swiss mice exposed to IDPN as a mouse lesion model for research in vestibular therapy and regeneration
This work was supported by the Spanish Ministry of Economy and Competitiveness (MINECO)—FEDER (grant numbers BFU2012-31164 and BFU2015-66109-R) and the Generalitat of Catalonia (grant number 2014 SGR 943)
Format: application/pdf
Accés al document: http://hdl.handle.net/10256/14067
Llenguatge: eng
Editor: Oxford University Press (OUP)
Col·lecció: info:eu-repo/semantics/altIdentifier/doi/10.1093/toxsci/kfw238
info:eu-repo/semantics/altIdentifier/issn/1096-6080
info:eu-repo/semantics/altIdentifier/eissn/1096-0929
És part de: info:eu-repo/grantAgreement/MINECO//BFU2012-31164/ES/DAÑO Y REPARACION VESTIBULAR EN LA OTOTOXICIDAD CRONICA: ETAPAS CELULARES, DEFICITS FISIOLOGICOS Y MECANISMOS MOLECULARES/
Drets: Tots els drets reservats
Matèria: Aparell vestibular
Vestibular apparatus
Toxicologia
Toxicology
Efectes secundaris dels medicaments
Drugs -- Side effects
Títol: Strain and Sex Differences in the Vestibular and Systemic Toxicity of 3,3’ -Iminodipropionitrile in Mice
Tipus: info:eu-repo/semantics/article
Repositori: DUGiDocs

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