Antioxidative, inflammatory and immune responses in hydrogen peroxide-induced liver injury of tilapia (GIFT, Oreochromis niloticus).

Oxidative stress has been implicated in the pathogenesis of many liver diseases in fish, but the molecular mechanism is still obscure. Here, we used hydrogen peroxide (H2 O2 ) as a reactive oxygen species (ROS) to induce liver injury and assess underlying molecular mechanism linking oxidative stress and liver injury in fish. Tilapia were injected with various concentrations of H2 O2 (0, 40, 120, 200, 300 and 400 mM) for 72 h. The blood and liver were collected to assay biochemical parameters and genes expression after 24, 48 and 72 h of injection. The results showed that treatments with higher H2 O2 levels (300 and/or 400 mM) significantly increased the levels of GPT, GOT, AKP and MDA, and apparently decreased the levels of TP, ALB, SOD, GSH, CAT, GST and T-AOC throughout of the 72 h. The gene expression data showed that treatments with 200, 300 and/or 400 H2 O2 suppressed Nrf2/keap1 pathway and its downstream genes including ho-1, nqo1 and gsta, activated inflammatory response via enhancing the mRNA levels of nf-κb, tnf-α, il-1β and il-8, and attenuating il-10 mRNA level, and caused immunotoxicity through downregulating the genes expression of c3, hep, lzm and Igm for 24, 48 and/or 72 h. Additionally, there was a mild or strong increase in levels of nrf2 and its subsequent antioxidant genes or enzymes such as ho-1, nqo1, gst, CAT and SOD in treatments with lower concentrations of H2 O2 (40 or 120 mM) for 24 and/or 48 h. Overall results suggested that H2 O2 hepatotoxicity was mainly concerned with lipid peroxidation, impairment antioxidant defense systems, inflammatory response and immunotoxicity, and Nrf2/Keap1 and NF-κB signaling pathways played important roles in oxidative stress-induced liver injury in fish.