Microplastics pollution is a global paradigm that raises concern in relation to environmental and human health. This study investigated toxic effects of microplastics and mercury in the European seabass (Dicentrarchus labrax), a marine fish widely used as food for humans. A short-term (96 h) laboratory bioassay was done by exposing juvenile fish to microplastics (0.26 and 0.69 mg/L), mercury (0.010 and 0.016 mg/L) and binary mixtures of the two substances using the same concentrations, through test media. Microplastics alone and mercury alone caused neurotoxicity through acetylcholinesterase (AChE) inhibition, increased lipid oxidation (LPO) in brain and muscle, and changed the activities of the energy-related enzymes lactate dehydrogenase (LDH) and isocitrate dehydrogenase (IDH). All the mixtures caused significant inhibition of brain AChE activity (64-76%), and significant increase of LPO levels in brain (2.9-3.4 fold) and muscle (2.2-2.9 fold) but not in a concentration-dependent manner; mixtures containing low and high concentrations of microplastics caused different effects on IDH and LDH activity. Mercury was found to accumulate in the brain and muscle, with bioaccumulation factors of 4-7 and 25-40, respectively. Moreover, in the analysis of mercury concentrations in both tissues, a significant interaction between mercury and microplastics was found. The decay of mercury in the water increased with microplastics concentration, and was higher in the presence of fish than in their absence. Overall, these results indicate that: microplastics influence the bioaccumulation of mercury by D. labrax juveniles; microplastics, mercury and their mixtures (ppb range concentrations) cause neurotoxicity, oxidative stress and damage, and changes in the activities of energy-related enzymes in juveniles of this species; mixtures with the lowest and highest concentrations of their components induced different effects on some biomarkers. These findings and other published in the literature raise concern regarding high level predators and humans consuming fish being exposed to microplastics and heavy metals, and highlight the need of more research on the topic.

Mercury toxicity mediated by different forms of mercury is a major health problem; however, the molecular mechanisms underlying toxicity remain elusive. We analyzed the effects of mercuric chloride (HgCl₂) and monomethylmercury (MeHg) on the proteins of the mammalian thioredoxin system, thioredoxin reductase (TrxR) and thioredoxin (Trx), and of the glutaredoxin system, glutathione reductase (GR) and glutaredoxin (Grx). HgCl₂ and MeHg inhibited recombinant rat TrxR with IC₅₀ values of 7.2 and 19.7 nm, respectively. Fully reduced human Trx1 bound mercury and lost all five free thiols and activity after incubation with HgCl₂ or MeHg, but only HgCl₂ generated dimers. Mass spectra analysis demonstrated binding of 2.5 mol of Hg²⁺ and 5 mol of MeHg⁺/mol of Trx1 with the very strong Hg²⁺ complexes involving active site and structural disulfides. Inhibition of both TrxR and Trx activity was observed in HeLa and HEK 293 cells treated with HgCl₂ or MeHg. GR was inhibited by HgCl₂ and MeHg in vitro, but no decrease in GR activity was detected in cell extracts treated with mercurials. Human Grx1 showed similar reactivity as Trx1 with both mercurial compounds, with the loss of all free thiols and Grx dimerization in the presence of HgCl₂, but no inhibition of Grx activity was observed in lysates of HeLa cells exposed to mercury. Overall, mercury inhibition was selective toward the thioredoxin system. In particular, the remarkable potency of the mercury compounds to bind to the selenol-thiol in the active site of TrxR should be a major molecular mechanism of mercury toxicity.

Significance: The thioredoxin (Trx) and glutathione (GSH) systems play important roles in maintaining the redox balance in the brain, a tissue that is prone to oxidative stress due to its high-energy demand. These two disulfide reductase systems are active in various areas of the brain and are considered to be critical antioxidant systems in the central nervous system (CNS). Various neuronal disorders have been characterized to have imbalanced redox homeostasis. Recent Advances: In addition to their detrimental effects, recent studies have highlighted that reactive oxygen species/reactive nitrogen species (ROS/RNS) act as critical signaling molecules by modifying thiols in proteins. The Trx and GSH systems, which reversibly regulate thiol modifications, regulate redox signaling involved in various biological events in the CNS. Critical Issues: In this review, we focus on the following: (i) how ROS/RNS are produced and mediate signaling in CNS; (ii) how Trx and GSH systems regulate redox signaling by catalyzing reversible thiol modifications; (iii) how dysfunction of the Trx and GSH systems causes alterations of cellular redox signaling in human neuronal diseases; and (iv) the effects of certain small molecules that target thiol-based signaling pathways in the CNS. Future Directions: Further study on the roles of thiol-dependent redox systems in the CNS will improve our understanding of the pathogenesis of many human neuronal disorders and also help to develop novel protective and therapeutic strategies against neuronal diseases. Antioxid. Redox Signal . 27, 989–1010.

The presence of microplastics and several other pollutants in the marine environment is of growing concern. However, the knowledge on the toxicity of mixtures containing microplastics and other contaminants to marine species is still scarce. The main goals of this study were to investigate the oxidative stress and lipid oxidative damage potentially induced by 96 h of exposure to mercury (0.010 and 0.016 mg/L), microplastics (0.26 and 0.69 mg/L), and mixtures of the two substances (same concentrations, full factorial) in the gills and liver of D. labrax juveniles, and the possible influence of microplastics on mercury bioconcentration (gills) and bioaccumulation (liver). The results indicate that the presence of microplastics in the water increased the concentration of mercury in gills and liver of D. labrax juveniles. Microplastics and mercury, alone and in mixtures, caused oxidative stress in both organs. Based on the total induction of antioxidant enzymatic activity, the type of toxicological interaction in fish exposed to the mixture containing the lowest concentration of the two substances was addition in gills, and addition or synergism in the liver. These results stress the need to further address the role of microplastics in the bioconcentration, bioaccumulation, and toxicity of other environmental contaminants in different species.

The main objectives of this study were to investigate the effects of a mixture of microplastics and mercury on Corbicula fluminea, the post-exposure recovery, and the potential of microplastics to influence the bioconcentration of mercury by this species. Bivalves were collected in the field and acclimated to laboratory conditions for 14 days. Then, a 14-day bioassay was carried out. Bivalves were exposed for 8 days to clean medium (control), microplastics (0.13 mg/L), mercury (30 µg/L) and to a mixture (same concentrations) of both substances. The post-exposure recovery was investigated through 6 additional days in clean medium. After 8 and 14 days, the following endpoints were analysed: the post-exposure filtration rate (FR); the activity of cholinesterase enzymes (ChE), NADP-dependent isocitrate dehydrogenase (IDH), octopine dehydrogenase, catalase, glutathione reductase, glutathione peroxidase and glutathione S-transferases (GST), and the levels of lipid peroxidation (LPO). After 8 days of exposure to mercury, the bioconcentration factors (BCF) were 55 in bivalves exposed to the metal alone and 25 in bivalves exposed to the mixture. Thus, microplastics reduced the bioconcentration of mercury by C. fluminea. Bivalves exposed to microplastics, mercury or to the mixture had significantly (p ≤ 0.05) decreased FR and increased LPO levels, indicating fitness reduction and lipid oxidative damage. In addition, bivalves exposed to microplastics alone had significant (p ≤ 0.05) reduction of adductor muscle ChE activity, indicating neurotoxicity. Moreover, bivalves exposed to mercury alone had significantly (p ≤ 0.05) inhibited IDH activity, suggesting alterations in cellular energy production. Antagonism between microplastics and mercury in FR, ChE activity, GST activity and LPO levels was found. Six days of post-exposure recovery in clean medium was not enough to totally reverse the toxic effects induced by the substances nor to eliminate completely the mercury from the bivalve's body. These findings have implications to animal, ecosystem and human health.