The molecular mechanisms of alpha-lipoic acid on ameliorating aflatoxin B1-induced liver toxicity and physiological dysfunction in northern snakehead (Channa argus)

This research aimed to evaluate the protective mechanism of alpha-lipoic acid (alpha-LA) on the food-borne aflatoxin B1 (AFB1) exposure-induced liver toxicity and physiological dysfunction in the northern snakehead (Channa argus). 480 fish (9.24 +/- 0.01 g) were randomly assigned to four treatment groups and fed with four experimental diets for 56 d including the control group (CON), AFB1 group (200 ppb AFB1), 600 alpha-LA group (600 ppm alpha-LA+200 ppb AFB1), and 900 alpha-LA group (900 ppm alpha-LA+200 ppb AFB1). The results revealed that 600 and 900 ppm alpha-LA attenuated AFB1-induced growth inhibition and immunosuppression in northern snakehead. 600 ppm alpha-LA significantly decreased the serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase levels, and AFB1 bioaccumulation, and attenuated the changes of hepatic histopathological and ultrastructure induced by AFB1. Moreover, 600 and 900 ppm alpha-LA significantly up -regulated phase I metabolism genes (cytochrome P450-1a, 1b, and 3a) mRNA expression, inhibited the levels of malondialdehyde, 8-hydroxy-2 deoxyguanosine and reactive oxygen species in the liver. Notably, 600 ppm alpha-LA significantly up-regulated the expression levels of nuclear factor E2 related factor 2 and its related downstream antioxidant molecules (heme oxygenase 1 and NAD(P)H: quinone oxidoreductase 1, etc.), increased the phase II detoxification enzyme-related molecules (glutathione-S-transferase and glutathione), antioxidant parameters (catalase and superoxide dismutase, etc.), and the expressions of Nrf2 and Ho-1 protein in the presence of AFB1 exposure. Furthermore, 600 and 900 ppm alpha-LA significantly reduced the characteristic indices of AFB1-induced endoplasmic reticulum stress (glucose-regulated protein 78 and inositol requiring enzyme 1, etc.), apoptosis (caspase-3 and cytochrome c, etc.) and inflammation (nuclear factor kappa B and tumor necrosis factor alpha, etc.), while increased the B-cell lymphoma-2 and inhibitor of kappa B alpha in the liver after being exposed to AFB1. To summarize, the above results indicate that dietary alpha-LA could modulate the Nrf2 signaling pathway to ameliorate AFB1-induced growth inhibition, liver toxicity, and physiological dysfunction in northern snakehead. Although the concentration of alpha-LA increased to 900 ppm from 600 ppm, the protective effects of the 900 ppm alpha-LA do not show an advantage over the 600 ppm alpha-LA, and even show inferiority in some respects. So that the recommended concentration of alpha-LA is 600 ppm. The present study provides the theoretical foundation for developing alpha-LA as the prevention and treatment of AFB1-induced liver toxicity in aquatic animals.