The mechanism of the neuroprotective effect of zinc against cadmium-induced behavioral impairments in male Wister rats: Focus on tryptophan degradation pathway, oxidative-inflammatory stress, and histologic evidence.

The present study investigated the attenuating effects of Zn following Cd-exposure in the activities/expression of indoleamine 2, 3-dioxygenase (IDO), tryptophan 2, 3-dioxygenase (TDO), oxidative-inflammatory response, behavioral indices and histologic architecture in cerebral cortex and hippocampus of male rats. Adult male Wistar rats were exposed to 200 μg/L and 100 μg/L of Cd and/or Zn in drinking water for 42 days. Cd exposure significantly increased IDO and TDO activities, IDO 1 protein expression, inflammatory response, with attendant disruption in antioxidant systems and concomitant elevation in malondialdehyde (MDA) levels in the cerebral cortex and hippocampus. Following Zn co-treatment, Cd-mediated increase in IDO 1 protein expression, IDO, and TDO activities, and decrease in antioxidant enzymes, and an increase in markers of inflammatory response and MDA production were significantly (p < 0.05) reversed compared with control. Moreover, altered behavioral indices and histological architecture of brain sections following Cd exposure was evidently (p < 0.05) prevented by Zn co-treatment relative to control. Overall, Cd-induced alterations in IDO 1 expression, IDO and TDO activities, oxidative-inflammatory response, behavioral indices, and histological architecture in the cerebral cortex and hippocampus of rats within the time course of the investigation were prevented by Zn co-treatment.