The ameliorative role of phlorotannin on aflatoxin B1-induced liver oxidative stress and mitochondrial injury is related to the activation of Nrf2 and Nrf1 signaling pathways in broilers

Abstract Background Aflatoxin B 1 (AFB 1 ) risks animal and human health, and the liver is considered the most crucial detoxification organ. Phlorotannin (PT) is a polyhydroxy phenol that has a wide range of biological activities, including anti-oxidation and hepatoprotection, which can promote the ability of liver detoxification. This study aimed to elucidate the protective effect of PT on AFB 1 -induced liver damage in broilers. Results In vivo experiment showed that the PT reduced AFB 1 content and AFB 1 -exo-8,9-epoxide DNA (AFBO-DNA) concentration in serum and liver ( P < 0.05), improved the histomorphology of liver and hepatic mitochondria, and activated nuclear factor erythroid 2-related factor 2 (Nrf2)-related antioxidant and detoxification pathway by upregulating the activities of antioxidant enzymes (catalase [CAT], glutathione S-transferase [GST]) and total antioxidant capacity (T-AOC) level ( P < 0.05), and inhibited the mRNA expression of CYP1A1 (cytochrome P450 family 1 subfamily A member 1) and phase II detoxification enzyme related genes ( GPX1 , GSTT1 , and NQO1 ) of broilers exposed to AFB 1 ( P < 0.05). Meanwhile, PT upregulated the Nrf1 pathway-related mitochondrial biosynthetic genes ( Nrf1 , mitochondrial transcription factor A [ TFAM ], mitofusin 1 [ MFN1 ]) in broilers fed AFB 1 contaminated diet ( P < 0.05). In vitro verification study suggested that the use of Nrf2/Nrf1 inhibitors suppressed the ameliorative role of PT on AFB 1 -induced liver injury of broilers, which was manifested in the mRNA expression of Nrf2 , NQO1 , GSTT3 , Nrf1 , TFAM , and other genes decreasing ( P < 0.05), and down-regulation of the protein expression of Nrf2, total and nucleus p-Nrf2, and total and nucleus p-Nrf1 ( P < 0.05). Conclusion The PT ameliorates oxidative stress and hepatotoxicity by activating the Nrf2-mediated phase II detoxification enzymes pathway and maintains mitochondrial homeostasis by activating the Nrf1 signaling pathway in broilers exposed to AFB 1 . Graphical Abstract