Tolerance to beta,beta'-iminodipropionitrile (IDPN)-induced neurobehavioural and vestibular toxicity in diabetic rats.

Abstract

The present investigation was undertaken to study the neurotoxic effects of beta,beta'-iminodipropionitrile (IDPN) in normal, diabetic and insulin-treated diabetic rats. Sprague-Dawley male rats were divided into five groups: control, IDPN, diabetes, diabetes plus IDPN and diabetes plus insulin plus IDPN. The diabetes was induced with a single i.p. injection of streptozotocin (50 mg kg(-1)). One month after the induction of diabetes, the rats were treated with IDPN (100 mg kg(-1), i.p.) daily for 11 days. One of the diabetic groups treated with IDPN also received daily injection of insulin (25 U kg(-1), s.c.), 1 h before IDPN. The rats were observed daily for abnormal head movements and circling. The grip strength of the forelimbs was also measured. In the IDPN group the dyskinetic symptoms appeared on the 8th day, whereas the onset of dyskinesia was on the 12th day in IDPN-treated diabetic rats. The incidence and severity of dyskinesia were significantly higher in IDPN-treated normal (non-diabetic) rats as compared to IDPN-treated diabetic rats. The treatment of diabetic rats with insulin normalized striatal dopamine (DA) turnover but partially reversed diabetes-induced protection against IDPN dyskinesia. There was severe degeneration of sensory hair cells in crista ampullaris of IDPN-treated normal rats, whereas the diabetic rats showed significant protection against IDPN-induced vestibular hair cell degeneration. In conclusion, our study clearly demonstrates that diabetic rats are resistant to IDPN-induced neurobehavioural and vestibular toxicity. The results also show that diabetes-induced protection against IDPN-induced dyskinesia can be partially reversed by insulin. The mechanism behind the decreased vulnerability of diabetic animals to IDPN remains to be resolved. Further studies are warranted to investigate this paradoxical phenomenon.