Programmed Effects in Neurobehavior and Antioxidative Physiology in Zebrafish Embryonically Exposed to Cadmium: Observations and Hypothesized Adverse Outcome Pathway Framework

Abstract

Non-communicable diseases (NCDs) are a major cause of premature mortality. Recent studies show that predispositions for NCDs may arise from early-life exposure to low concentrations of environmental contaminants. This developmental origins of health and disease (DOHaD) paradigm suggests that programming of an embryo can be disrupted, changing the homeostatic set point of biological functions. Epigenetic alterations are a possible underlying mechanism. Here, we investigated the DOHaD paradigm by exposing zebrafish to subtoxic concentrations of the ubiquitous contaminant cadmium during embryogenesis, followed by growth under normal conditions. Prolonged behavioral responses to physical stress and altered antioxidative physiology were observed approximately ten weeks after termination of embryonal exposure, at concentrations that were 50–3200-fold below the direct embryotoxic concentration, and interpreted as altered developmental programming. Literature was explored for possible mechanistic pathways that link embryonic subtoxic cadmium to the observed apical phenotypes, more specifically, the probability of molecular mechanisms induced by cadmium exposure leading to altered DNA methylation and subsequently to the observed apical phenotypes. This was done using the adverse outcome pathway model framework, and assessing key event relationship plausibility by tailored Bradford-Hill analysis. Thus, cadmium interaction with thiols appeared to be the major contributor to late-life effects. Cadmium-thiol interactions may lead to depletion of the methyl donor S-adenosyl-methionine, resulting in methylome alterations, and may, additionally, result in oxidative stress, which may lead to DNA oxidation, and subsequently altered DNA methyltransferase activity. In this way, DNA methylation may be affected at a critical developmental stage, causing the observed apical phenotypes.

Investigating the Predictive Power of Three Potential Sublethal Endpoints for the Fathead Minnow Fish Embryo Toxicity Test: Snout-Vent Length, Eye Size, and Pericardial Edema

“…The general lack of alteration in C-start behaviors was unexpected as previous evidence suggests that Cd, PFOS, and DCA can all alter neurodevelopment. For example, Cd has been shown to impact behaviors such as place preference and hyperactivity . Likewise, PFOS has been shown to negatively impact the average number of neuromast cells present along the lateral line of zebrafish embryos, which likely impacts C-start behavior, and is known to alter C-start responses of juvenile qingbo (Spinibarbus sinensis) .…”

Protection Against Cadmium-Induced Abnormalities and Hepatotoxicity in ovo by Allium sativum

“…Mechanism of toxicity of cadmium , like other metals is oxidative stress, DNA damage, ER stress lipoperoxidation, mitochondrial fragmentation, and cell death (Xu et al, 2013;Chen et al, 2015;Nair et al, 2013;Wei et al, 2014;Jamakala and Rani, 2015;Kim et al, 2015;Veeriah et al, 2015;Ruiter et al, 2016;Xu et al, 2017) through either MAPK pathways (Yiran et al, 2013), or by decreasing expression and activity of SIRT3 protein and promotes the acetylation of superoxide dismutase 2 (Guo et al, 2014;Pi et al, 2015).…”

Applicability of disulfide-polymer particles surface embedded on alginate beads for cadmium removal from airport derived stormwater

“…De-icing Fluid Ethylene glycol based fluid 240 [6] Propylene glycol based fluid 6.7 [6] Aircraft de-icing/anti-icing fluids with 80% glycols 1500 [3]…”

“…The presence of heavy metal ions in water has several adverse effects on living organisms. It has been established that among the heavy metal pollutants, cadmium has carcinogenic potential to humans and experimental animals [5], [6]. Various cadmium concentrations in airport runoff occur in a range of 1 -450 µg/L in different international airports, despite that the accepted flow limit for airports regulations is 0.2 µg/L ( Table 1).…”