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

Biol Trace Elem Res. 2024 Mar;202(3):1140-1149. doi: 10.1007/s12011-023-03752-7. Epub 2023 Jul 1.

Abstract

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.

Keywords: Immunotoxicity; Indoleamine 2,3-dioxygenase; Oxido-inflammatory stress; Spleen.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes
  • Cadmium / pharmacology
  • Drinking Water*
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / pharmacology
  • Male
  • Oxidative Stress
  • Rats
  • Rats, Wistar
  • Spleen / metabolism
  • T-Lymphocytes / metabolism
  • Zinc* / metabolism
  • Zinc* / pharmacology

Substances

  • Zinc
  • Cadmium
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Drinking Water