Zinc alleviates arsenic-induced muscle injury in common carp through modulation of oxidative stress and related signaling pathways.

Arsenic (As) pollution in aquatic ecosystems presents a significant risk to fish health and to the viability of aquaculture. Although extensive documentation of the effects of arsenic poisoning has been made in several fish organs, its effects on the most important edible portion, skeletal muscle, remain relatively poorly understood. The purpose of this study was to evaluate the protective effect of zinc (Zn) and to determine how arsenic (As) causes muscle injury in common carp (Cyprinus carpio). Common carp were exposed to arsenic alone and in combination with zinc for 30 days. To explore the underlying mechanisms, histopathological investigation, reverse transcription quantitative polymerase chain reaction (RT-qPCR), Western blotting, and network toxicology were used. At the same time, arsenic exposure induced significant structural damage in the muscle of carp along with several other effects such as oxidative stress, inflammatory responses, endoplasmic reticulum (ER) stress, autophagy, and apoptosis. Arsenic particularly affected the antioxidant defense by the down-regulation of genes related to antioxidant defense, and by affecting the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. In addition, arsenic enhanced the inflammatory responses through nuclear factor kappa B (NF-κB) and promoted autophagy and apoptotic signaling. Zinc supplementation proved to be of great value and significantly reduced these pathogenic changes by restoring antioxidant capacity, blocking inflammatory signaling, and regulating autophagy and apoptosis-related pathways. A network toxicology analysis revealed that networks associated with oxidative stress, such as the phosphoinositide 3-kinase-protein kinase B (PI3K-Akt) signaling pathway and forkhead box O (FoxO) signaling pathway, were affected by arsenic and that zinc alleviated arsenic-induced muscle toxicity. These data together suggest that zinc is effective in protecting the muscle of carp against the damage caused by arsenic by regulating redox-related signaling pathways. These results contribute to the understanding of the mechanism of action of the toxicity of heavy metals in fish muscle and the potential of zinc as a protective agent against arsenic toxicity in aquaculture fish.