Mitigation of Cadmium Toxicity through Modulation of the Frontline Cellular Stress Response

Cadmium (Cd) is an environmental toxicant of public health significance worldwide. Diet the main Cd exposure source in non-occupationally exposed and non-smoking populations. Metal transporters for iron (Fe), zinc (Zn), calcium (Ca), manganese (Mn) are involved assimilation distribution to cells throughout body. Due extremely slow elimination rate, most retained by cells, where it exerts toxicity through its interaction with sulfur-containing ligands, notably thiol (-SH) functional group cysteine, glutathione, many Zn-dependent enzymes transcription factors. The simultaneous induction heme oxygenase-1 metal-binding protein metallothionein adversely affected cellular redox state caused dysregulation Fe, Zn, copper. Experimental data indicate that causes mitochondrial dysfunction via disrupting metal homeostasis this organelle. present review focuses on adverse metabolic outcomes chronic low-dose Cd. Current epidemiologic raises risk type 2 diabetes several mechanisms, such as increased oxidative stress, inflammation, adipose tissue dysfunction, insulin resistance, dysregulated intermediary metabolism. stress response mechanisms involving catabolism heme, mediated -2 (HO-1 HO-2), may mitigate cytotoxicity products their physiologic degradation, bilirubin carbon monoxide, have antioxidative, anti-inflammatory, anti-apoptotic properties.