Histological insights in iminodipropionitrile-induced toxicity in rats

Iminodipropionitrile (IDPN) is a prototype nitrile compound that produces excitation, chorea and circling (ECC) syndrome in rodents. Previous studies have implicated vestibular hair cell degeneration in IDPN-induced behavioral abnormalities. Although the pathological changes in vestibular labyrinth of IDPN-treated rats are well documented, the effects of IDPN on other organ systems are not clearly understood. We therefore examined the histopathological alterations in inner ear, brain, liver and kidneys of rats exposed to IDPN. Adult male Wistar rats were divided into two groups of six animals each. Control rats received normal saline whereas the IDPN group was treated with IDPN (100 mg/kg, i.p.) daily for 7 days. All the animals were carefully observed for any behavioral abnormality and the dyskinetic movements including the vertical and horizontal head weaving, circling and backward walking were quantified. The animals were sacrificed on day 9 and the samples of cochlea, brain, liver and kidney were collected for histopathology. The results showed a direct correlation between the severity of behavioral deficits and the cellular damage in crista ampullaris in IDPN-treated rats. Histopathology of liver was severely influenced by IDPN treatment, leading to vacuolization of cytoplasm, distorted sinusoids, infiltration of mononuclear cells and necrotic zones. However, the severity of hepatic damage in IDPN-treated rats was independent of the magnitude of vestibular hair cell degeneration as well as the severity of behavioral deficits. Administration of IDPN in the vestibulotoxic doses did not produce any histological changes in the brain cortex and kidneys of rats.