Environmental Pollution

Volume 253, October 2019, Pages 741-748
Environmental Pollution

The cardiotoxicity of the common carp (Cyprinus carpio) exposed to environmentally relevant concentrations of arsenic and subsequently relieved by zinc supplementation

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Arsenic cardiac accumulation induces ROS burst and collapse of antioxidant system.

Apoptosis and autophagy are induced under arsenic stress.

Zinc antagonizes cardiotoxicity of arsenic via MAPK and PI3K/Akt/mTOR pathways.


Waterborne exposure to arsenic trioxide (As2O3) is inevitable due to its widespread industrial and agricultural applications. Oxidative stress and cascaded programmed cell death is now hypothesized to be the dominant mechanisms of arseniasis evidenced in vivo and in vitro. This study aimed to explore the interaction of divalent zinc ion (Zn2+), an efficient reactive oxygen species (ROS) scavenger with arsenite in the heart of common carp, and extensively investigated the exact signaling molecules involved. Significant induction of cardiotoxicity including oxidative stress, apoptosis and autophagy was evident in heart tissues following arsenite exposure (P < 0.05). The dissipation of antioxidant enzymes (SOD and CAT) was induced by ROS burst, leading to oxidative damage and lipid peroxidation (MDA). Arsenite induced classic apoptotic hallmarks, characterized by chromatin degradation and subsequent formation of clumps adjacent, and elevated expression of Bax/Bcl-2 and Caspase family, and also increased autophagic flux evidenced by accelerated formation (LC3) and degradation (p62) of autophagosomes. PI3K/Akt/mTOR pathway was phosphorylated inhibited, while MAPK signaling (p38, ERK and JNK) displayed elevated phosphorylation levels in arsenite-exposed heart tissues. In contrast, above phenomena were effectively inhibited by Zn2+, which supplement attenuated arsenite-induced myocardial toxicity through inhibition of apoptosis and autophagy via PI3K/Akt/mTOR pathway, as well as suppressing intracellular ROS cluster via activating antioxidative system via MAPK pathway. Our results provided experimental explanation and evidences for cardiotoxicity of arsenite. Furthermore, our findings hint that the application of zinc preparations may provide a candidate for the prevention and treatment for arsenic poisoning.


Environmental pollution
Aquatic animal

This paper has been recommended for acceptance by Dr. Jörg Rinklebe.


Hongjing Zhao and Yu Wang contributed equally to this article.