Zinc Ameliorates Cadmium-Induced Immunotoxicity by Modulating Splenic Immunosuppressive Indoleamine 2,3-Dioxygenase Activity, Hematological Indices, and CD4+ T Cells via Inhibition of Cadmium Uptake in Male Wistar Rats.

Cadmium (Cd)-induced immunotoxicity has become a matter of public health concern owing to its prevalence in the environment consequently, great potential for human exposure. Zinc (Zn) has been known to possess antioxidant, anti-inflammatory, and immune-boosting properties. However, the ameliorating influence of Zn against Cd-induced immunotoxicity connecting the IDO pathway is lacking. Adult male Wistar rats were exposed to normal drinking water with no metal contaminants (group 1), group 2 received drinking water containing 200 µg/L of Cd, group 3 received drinking water containing 200 µg/L of Zn, and group 4 received Cd and Zn as above in drinking water for 42 days. Cd exposure alone significantly triggered the splenic oxidative-inflammatory stress, increased activities of immunosuppressive tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenases (IDO) activities/protein expression, and decreased CD4+ T cell count, and a corresponding increase in the serum kynurenine concentration, as well as alterations in the hematological parameters and histologic structure when compared with the control (p < 0.05). Zn alone did not have any effect relative to the control group while co-exposure significantly (p < 0.05) assuaged the Cd-induced alterations in the studied parameters relative to the control. Cd-induced modifications in IDO 1 protein expression, IDO/TDO activities, oxidative-inflammatory stress, hematological parameters/CD4+ T cell, and histological structure in the spleen of rats within the time course of the investigation were prevented by Zn co-exposure via inhibition of Cd uptake.

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.