Chronic exposure of hydrogen peroxide alters redox state, apoptosis and endoplasmic reticulum stress in common carp (Cyprinus carpio)

Hydrogen peroxide (H2O2) appears to be ubiquitous in natural water. Higher level of H2O2 can cause physiological stress, immunosuppression and even death in aquatic animals, but the physiological and molecular mechanisms of H2O2 toxicity are not well studied. Thus, the aim of the present study was to exposure potential toxic mechanisms of H2O2 via assessing the effects on redox state, apoptosis and endoplasmic reticulum (ER) stress in common carp. The fish were subjected to four concentrations of H2O2 (0, 0.25, 0.5 and 1 mM) for 14 days. And then, the tissues including blood, liver, muscle, gills, intestines, heart, kidney and spleen were collected to measure biochemical parameter and gene expression. The results showed that H2O2 exposure suppressed the majority antioxidative parameters in serum, liver, muscle and intestines, but enhanced T-SOD, CAT and T-AOC levels in gills. In all tested tissues, the MDA content was significantly promoted by H2O2 exposure. The oxidative stress-related genes including nrf2, gst alpha, sod, cat and/or gpx1 were upregulated in liver, gills, muscle, intestines, and/or kidney, but downregulated in heart after H2O2 exposure. Moreover, the ho-1 mRNA level was inhibited by H2O2 exposure in all tissues except intestines and spleen. After 14 days of exposure, H2O2 induced ER stress and initiated IRE1 and PERK pathways, which activated downstream genes, including chop, grp78 and/or xbp1s, to regulate UPR in liver, gills, muscle and/or heart. Meanwhile, H2O2 exposure activated MAPK pathway to regulate mitochondria-related genes including bcl-2, bax and cytc, which further triggered cas8, cas-9 and cas-3, and accelerated apoptosis in liver, gills, muscle and heart. Importantly, in different tissues, the genes associated with oxidative stress, ER stress and apoptosis showed a different influence, and more significant influence was observed in the muscle, gills and liver. Overall results suggested that long-term H2O2 exposure induced oxidative stress, ER stress and apoptosis in the majority of tested tissues of common carp. The Nrf2, IRE1, PERK and MAPK pathways played important roles in H2O2-induced toxicity in fish. These data enriched the toxicity mechanism of H2O2 in fish, which might contribute to the risk assessment of H2O2 in aquatic environment.