Modification of acrylamide neuropathy in rats by selected factors

A modified rotarod technique was used to determine whether dietary deficiencies in pyridoxine or thiamine, bilateral adrenalectomy or cortisol treatment and pretreatment with microsomal enzyme inducers (DDT or phenobarbital) would modify the course of onset and recovery from functional acrylamide neuropathy in rats. Neither pyridoxine or thiamine deficiency nor daily injections of cortisol had any measurable effect on the cumulative dose of acrylamide required to produce functional impairment. Although adrenalectomized animals were more susceptible to acrylamide, the effect seemed nonspecific. The total cumulative doses of acrylamide required to produce neurologic deficit in DDT- and phenobarbital-pretreated rats were 520 and 600 mg/kg, respectively, compared to 360 mg/kg for the controls. Hepatic in vitro metabolism of acrylamide was studied to determine whether the observed delay could be explained by an increased capacity of the liver to detoxify acrylamide. There was a greater loss of acrylamide from incubation mixtures containing 9000 g supernatants from phenobarbital-pretreated rat livers than from control livers. Histologic studies of peripheral nerves from acrylamide-treated rats revealed that at the time of onset of functional impairment young and phenobarbital-pretreated adult rats had severe peripheral nerve damage, while no discernible peripheral nerve injury was seen in unpretreated adult rats.