Enhanced Uptake of Arsenic Induces Increased Toxicity with Cadmium at Non-Toxic Concentrations on Caenorhabditis elegans

Abstract

Cadmium (Cd) and arsenic (As) are widely distributed pollutants that co-exist in the environment; however, their joint toxicity on living organisms is still largely unknown. In this study, we explored the joint toxicity of concurrent exposure to Cd and different As species at low concentrations on Caenorhabditis elegans (C. elegans) in comparison to single exposures. Endpoints such as germ cell apoptosis, the number of oocytes, brood size, and the life span were employed to evaluate the combined effects of Cd and As on exposed C. elegans from L3 or L4 stages. Our results showed that concurrent exposure to non-toxic concentrations of Cd and As caused the synergy of reproductive and developmental toxicity. The presence of Cd promoted the accumulation of As in both germline and intestine detected by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Although a conversion of As(III) to As(V) was detected as dependent on pH according to the microenvironment of the intestine in the worm, there was no significant difference of toxicity in C. elegans concurrently exposed to Cd and different As species. Using loss-of-function mutant strains, As was deemed responsible for the enhanced joint toxicity, and in which gcs-1 played a key protective role. These data help to better evaluate the comprehensive adverse effects of concurrent exposure of heavy metals at low concentrations on living organisms in the environment.

Juggling cadmium detoxification and zinc homeostasis: A division of labour between the two C. elegans metallothioneins

“…6 D); therefore it would be misleading to deem MTL-1 to be “zinc-specific”. However, we have also demonstrated that when both proteins are simultaneously present in vitro , Cd 2+ partitions overwhelmingly into MTL-2, leaving MTL-1 largely populated with Zn 2+ ( Pei et al, 2022 ), in full accordance with measured affinity constants: As previously stated, the average stability constant for Cd 7 MTL-1 (log K = 13.1) is almost two orders of magnitude lower than that of Cd 6 MTL-2 (log K = 15.0) (Hall et al). These considerations emphasise the important concept of relative affinities ( Foster and Robinson, 2011 ).…”

“…In contrast, LA-ICP-MS returned negligible background signal for the cadmium isotope 111 Cd and thus was applied to measure the accumulation of cadmium in individual worms. The zinc (150 μM) and cadmium (30 μM) doses chosen for this study are based on a previous publication ( Anderson et al, 2001 ) and reflect equi-toxicity, at least in terms of reproductive performance, a key lifecycle endpoint and sensitive indicator of metal toxicity ( Pei et al, 2022 ) and are within the concentrations found in natural environments. It should be noted that, prior to any quantification, the intestinal lumen was allowed to clear to ensure the removal of free-floating metals.…”

“…S13 ), and their Zn 2+ and Cd 2+ affinities were determined by competition with 5F-BAPTA and compared to the corresponding wild-type data ( Fig. 6 D (Hall et al; Pei et al, 2022 );).…”

Associations of Heavy Metals with Activities of Daily Living Disability: An Epigenome-Wide View of DNA Methylation and Mediation Analysis

“…found that cadmium and arsenic can synergistically lead to reproductive and developmental toxicity of C. elegans . 48 The interaction between cadmium and arsenic is related to physicochemical properties and toxic mechanisms. It was found that both cadmium and arsenic are positively charged ions, which have high affinity for electron-rich thiol and selenol residues in proteins, and can stably bind to them, affecting protein and enzyme activities.…”

Research trends in Caenorhabditis elegans and aging from 2004 to 2023: a bibliometric analysis.

“…For instance, mutant SJ4058 [hsp-60::GFP + lin-15(+)] and CF1553 [(pAD76) sod-3p::GFP + rol-6(su1006)] provide valuable tools for investigating protein dynamics in vivo [40][41] . The Stress Resistance model of C. elegans can also be applied in the realm of environmental protection research, encompassing investigations on excessive heavy metal contamination, plastic pollution, soil and water pollution, among other elds [42][43][44] .…”