Astaxanthin attenuates AFB1-induced hepatotoxicity by activating Nrf2 and inhibiting the NF-κB signaling pathway
Kai Kang, Yueying Zhang, Xie WeiTian, Wanyun Ma, Jinjun Chen, Zhibao Chen
Abstract
Aflatoxin B1 (AFB1)-induced hepatotoxicity is a common toxic disease in poultry farming. However, there is currently a lack of effective pharmaceutical interventions for treating AFB1. Astaxanthin (AST), a natural carotenoid, exhibits potent antioxidant and immune-enhancing properties. In this study, the effect of AST on AFB1-induced hepatotoxicity was determined using chick embryo liver cells (CELs). The CCK-8 assay results showed that AST significantly attenuated the decrease in viability of CEL cells induced by AFB1, and reduced the activity of the enzymes GOT, GPT, and ALP (P < 0.01). Moreover, AST significantly reduced the AFB1-induced ROS, attenuated the increase in malondialdehyde (MDA), and attenuated the decrease in superoxide dismutase (SOD) and glutathione (GSH) (P < 0.01). Further, the western blot results showed that AST activated the nuclear factor erythroid-2 related factor 2 (Nrf2) signaling pathway, decreased the expression of kelch-1ike ECH-associated protein l (Keap-1), and increased the expression of Nrf2 and its downstream proteins glutamate-cysteine ligase catalytic subunit(GCLC), glutamate-cysteine ligase modifier subunit (GCLM), heme oxygenase-1(HO-1) and NAD(P)H: quinone oxidoreductase (NQO1)(P < 0.01). Furthermore, AST inhibited the expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) induced by AFB1 (P < 0.01). Western blot results showed that AST inhibited the nuclear factor-κB (NF-κB) pathway induced by AFB1 by reducing the phosphorylation of the P65 and IκB proteins (P < 0.01). In summary, these findings suggested that AST can be used as a candidate pharmaceutical to protect against AFB1-induced hepatotoxicity. AST protected the liver cells by effectively attenuating AFB1-induced oxidative stress and the inflammatory response.