In vitro and in vivo approaches to assess atherosclerosis following exposure to low-dose mixtures of arsenic and cadmium

Toxicol Appl Pharmacol. 2023 Nov 18;481:116763. doi: 10.1016/j.taap.2023.116763. Online ahead of print.ABSTRACTWorldwide, millions of people are co-exposed to arsenic and cadmium. Environmental exposure to both metals is linked with a higher risk of atherosclerosis. While studies have characterized the pro-atherosclerotic effects of arsenic and cadmium as single agents, little is known about the potential effects of metal mixtures, particularly at low doses. Here, we used a combination of in vitro and in vivo models to assess the effects of low-dose metals individually and as mixtures on early events and plaque development associated with atherosclerosis. In vitro, we investigated early pro-atherogenic changes in macrophages and endothelial cells with metal treatments. The combined cytotoxic effects of both metals at low concentrations were dose interactive, specifically, synergistic in macrophages, but antagonistic in endothelial cells. Despite this differential behavior across cell types, the mixtures did not initiate early pro-atherogenic events: neither reactive oxygen species generation in macrophages nor adhesion molecule expression on endothelial cells. In vivo, we utilized the well-characterized hyperlipidemic apolipoprotein E knock-out (ApoE-/-) mouse model. Previously, we have shown that low concentrations of arsenic (down to 10 ppb) enhance atherosclerosis in ApoE-/- mice. This model has also been used with cadmium to demonstrate pro-atherogenic effects, although a...
Source: Toxicology and Applied Pharmacology - Category: Toxicology Authors: Source Type: research