AUTHOR=Wu Fengyang , Wang Fengxia , Tang Zhaohong , Yang Xinyu , Liu Yanhua , Zhao Man , Liu Shudong , Han Shuaijuan , Zhang Zhisheng , Chen Baojiang 

TITLE=Quercetagetin alleviates zearalenone-induced liver injury in rabbits through Keap1/Nrf2/ARE signaling pathway

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1271384

DOI=10.3389/fphar.2023.1271384

ISSN=1663-9812

ABSTRACT=<p><bold>Introduction:</bold> This study aimed to assess the alleviative effect of quercetagetin (QG) on zearalenone (ZEN)-induced liver injury in rabbits.</p><p><bold>Methods:</bold> Ninety 41-day-old healthy Hyla rabbits were randomly assigned into three groups, including a control (fed with basic diet), ZEN addition group (fed with basic diet + 600 μg/kg ZEN), and ZEN + QG addition group (fed with basic diet + 600 μg/kg ZEN + 100 mg/kg QG), with 30 rabbits per group. The duration of the experiment was 28 days.</p><p><bold>Results:</bold> The results revealed no significant differences in the average daily gain, average daily feed intake, the gain to feed ratio and the liver, kidney and spleen organ indexes (<italic>p</italic> &gt; 0.05) between the rabbits across the three groups. However, the sacculus rotundus index of the rabbits in the control group was significantly higher than that in the ZEN + QG group (<italic>p</italic> &lt; 0.05). The intake of ZEN-contaminated diet also significantly increased the activities or levels of alanine transaminase, alkaline phosphatase, total bile acid (TBA), total bilirubin, malondialdehyde, and interleukin-4 (IL-4) and enhanced the abundance of kelch-like ECH-associated protein 1 <italic>(Keap1)</italic>, heat shock protein 70 <italic>(HSP70)</italic> and cysteine-aspartic acid protease-3 <italic>(Caspase-3)</italic> mRNA in the blood or liver tissue in ZEN group, compared to the control group (<italic>p</italic> &lt; 0.05). On the contrary, the activities or levels of immunoglobulin A, complement 3, total antioxidant capacity, glutathione peroxidase (GSH-Px), superoxide dismutase, interleukin-10, and the abundance of nuclear factor E2-related factor 2 <italic>(Nrf2)</italic> and heme oxygenase-1 <italic>(HO-1)</italic> mRNA were significantly decreased (<italic>p</italic> &lt; 0.05). Supplementing the diet with QG still maintained significantly higher levels of TBA and IL-4, and the abundance of <italic>GSH-Px, HSP70, IL-4,</italic> and <italic>Caspase-3</italic> mRNA in the blood and liver of rabbits in the ZEN + QG group than in the control group (<italic>p</italic> &lt; 0.05). At the same time, the other indicators were restored to levels in the control group (<italic>p</italic> &gt; 0.05).</p><p><bold>Discussion:</bold> In conclusion, QG alleviated the ZEN-induced oxidative damage and liver injury caused by inflammatory reaction through the Keap1-Nrf2-antioxidant response element (ARE) signal pathway, which protected the liver. This study revealed the alleviative effect of QG on the hepatotoxicity of ZEN in rabbits for the first time, providing a new perspective for applying QG and developing a ZEN antidote.</p>