Zinc-Mediated Endoplasmic Reticulum Stress and Metallothionein Alleviate Arsenic-Induced Cardiotoxicity in Cyprinus Carpio.

Abstract

Arsenic (As) is a natural component of the Earth's crust, and its inorganic form is highly toxic. The problem of As pollution in water is extremely urgent, and its impact on aquatic organisms should be widely considered. Here, 120 common carp were selected as the test subjects and were exposed to environmentally relevant concentrations of As (2.83 mg L^- 1) for 30 days. Histomorphological observations showed the adverse effects of As on the heart: irregular arrangement of myocardial fibers, rupture of muscle fiber bundles, inflammatory infiltration, and hemorrhages. Mechanistically, abnormal expression of factors related to As-induced inflammation (TLR4/MYD88/NF-κB pathway), endoplasmic reticulum stress (CHOP, GRP78, ATF6, PERK, IRE1) and oxidative stress (SOD, CAT, Nrf2, HO-1) was observed. Then, we tried to find a protective agent against As-induced myocardial injury. As one of the important metal elements for maintaining cell growth and immunity, zinc (Zn, 1 mg L^- 1) significantly alleviated the pathological abnormalities induced by As, and the changes in physiological and biochemical indices in response to As exposure were significantly alleviated by Zn administration, which was accompanied by the restoration of metallothionein (ZIP8, Znt1, Znt5, Znt7) and heat shock protein (HSP60, HSP70, HSP90) expression. These results suggest for the possibilty of developing Zn as a candidate therapeutic agent for As induced aquatic toxicology.