Mitigation mechanism of α-LA on AFB1-induced hepatocyte injury in snakehead fish (Channa argus): A potential substance

Abstract

In order to explore the mechanisms of α-Lipoic acid (α-LA) in mitigating aflatoxin B1 (AFB1)-induced hepatocyte injury in snakehead fish (Channa argus), a hepatocyte injury model induced by AFB1 (tested concentration: 0.12 μM; incubation duration: 24 h) was established in this study. Subsequently, the α-LA (100, 200, and 400 μM) and ML385 (2 μM) were further selected for 24 h and 4 h intervention, respectively. The results found that the α-LA intervention significantly enhanced the proliferation rate and the levels of GST, GSH, and GSH-Px of the hepatocytes (P < 0.05), significantly reduced the biochemical parameters (ALP, AST, LDH, and ALT), and the contents of MDA, ROS, and 8-OHdG of the hepatocytes (P < 0.05). At gene and protein levels, α-LA significantly ameliorated the AFB1-induced down-regulation of mRNA levels of cyp1a, cyp1b, and cyp3a, and significantly ameliorated the AFB1-induced up-regulation of mRNA levels of perk, grp78, chop, ire1, il-1β, nf-κb, bax, cas-3 and cyt-c, and the protein expressions of Grp78 (cytosolic) and Cyt-c (cytoplasmic) (P < 0.05). Also, α-LA significantly ameliorated the AFB1-induced down-regulation of mRNA levels of nrf2, nqo-1, gst, gsh-px, and ho-1 in hepatocytes (P < 0.05), and significantly ameliorated the AFB1-induced down-regulation of Nrf2 in hepatocytes, cytoplasm, and nucleus, and of Ho-1 protein expression in hepatocytes (P < 0.05). On this basis, the effects of α-LA on AFB1-induced metabolic inhibition, oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis were significantly attenuated by inhibition of Nrf2 protein using a specific inhibitor, ML385. In summary, α-LA alleviated hepatocyte injury in snakehead fish caused by AFB1 via activating the Nrf2 signaling pathway, and the optimal concentration was 200 μM. This study provides a new perspective and direction for the prevention and control of AFB1-induced liver injury in fish, and provides a theoretical basis for the solution of liver injury in fish in actual production.