Pattern of neurobehavioral and organ-specific toxicities of β, β'-iminodipropionitrile in mice

Abstract

Introduction: β, β'-iminodipropionitrile (IDPN) is a synthetic nitrile that produces a permanent movement disorder in rodents. Although IDPN-induced vestibular pathology is well documented, the mode of IDPN interaction with other organ systems is poorly understood. We examined the behavioral signs and histopathological changes in the vestibular labyrinth, brain, liver and kidneys of mice exposed to IDPN. Material and methods: Adult male SWR/J mice were divided into 2 groups of 6 animals each. One group of mice received normal saline (control group) and the other group was treated with IDPN (400 mg/kg, i.p.) daily for 7 days. Dyskinetic movements including vertical and horizontal head weaving, circling and backward walking were quantified on days 7, 8 and 9. Results: We observed a direct correlation between the severity of IDPN-induced behavioral deficits and the degeneration of vestibular hair cells in the crista ampullaris of mice. The brain cortex of both groups appeared similar, whereas the kidney histopathology revealed mild nephrotoxicity in some of the IDPN-treated mice. Administration of IDPN caused severe hepatotoxicity, but the intensity of hepatic damage was not correlated with the severity of behavioral deficits. Conclusions: Degeneration of vestibular sensory hair cells plays an important role in the development of IDPN-induced behavioral deficits in mice. Exposure to IDPN also caused severe hepatotoxicity which was independent of the behavioral symptoms. These findings could be of potential relevance to human health, particularly after the observation that IDPN not only causes a movement disorder but also produces acute liver injury.