Effects of arsenic and heavy metals on metabolic pathways in cells of human origin: Similarities and differences

Toxicol Rep. 2021 May 31:8:1109-1120. doi: 10.1016/j.toxrep.2021.05.015. eCollection 2021.


Various anthropogenic and natural events over the years have gradually increased human exposure to various heavy metals. Several of these heavy metals including cadmium, mercury, nickel, chromium, and the metalloid arsenic among others, have created major public health concerns for their high level of toxicities. Identification of the general as well as the differentially affected cellular metabolic pathways will help understanding the molecular mechanism of different heavy metal-induced toxicities. In this study, we analyzed 25 paired (control vs. treated) transcriptomic datasets derived following treatment of various human cells with different heavy metals and metalloid (arsenic, cadmium, chromium, iron, mercury, nickel and vanadium) to identify the affected metabolic pathways. The effects of these metals on metabolic pathways depend not only on the metals per se, but also on the nature of the treated cells. Tissue of origin, therefore, must be considered while assessing the effects of any particular heavy metal or metalloid. Among the metals and metalloid, arsenic appears to have relatively more pleiotropic influences on cellular metabolic pathways including those known to have association with diabetes. Although only two stem cell derived datasets are included in the current study, effects of heavy metals on these cells appear to be different from other mature cells of similar tissue origin. This study provides useful information about different heavy metal affected pathways, which may be useful in further exploration using wet-lab based techniques.

Keywords: Arsenic; Cadmium; Cell line; Chromium; Heavy metal; Human; Metabolic pathway.