Wang Xinghe, He Yang, Tian Jinlong, Muhammad Ishfaq, Liu Mingchun, Wu Changde, Xu Chang, Zhang Xiaohuan
College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, Liaoning 110866, PR China.
Fuxin Higher Training College, Fuxin, Liaoning 123000, PR China.
Ecotoxicol Environ Saf. 2021 Aug 17;224:112624. doi: 10.1016/j.ecoenv.2021.112624.
Aflatoxin B1 (AFB1) causes oxidative stress and hepatocyte apoptosis through its epoxidized metabolite AFBO, which is catalyzed by CYP450 enzymes. Ferulic acid (FA) is a phenolic acid commonly found in plants and is known for its antioxidant capacity. However, the role of FA in AFB1-induced liver injury is still elusive. In this study, rats were exposed to AFB1 and simultaneously treated with FA for 30 days. The results showed that I) FA alleviated the histopathological changes induced by AFB1, inhibited the elevation of serological indexes induced by AFB1, and reduced the production of AFBO in liver. II) AFB1-induced increase in CYP450 expression was significantly reduced by FA. The molecular docking results of FA and CYP2A6 showed high fitness score and interaction. III) FA obviously inhibited the production of MDA, and significantly activated the Nrf2/GST pathway and antioxidant enzymes (SOD and GST). IV) AFB1-induced hepatocyte apoptosis, the high expression of p53, bax, cyt-c, caspase-9, caspase-3, and the low expression of bcl-2 were all restored by FA. It has been suggested from these results that FA proved effective against AFB1-induced liver damage in rats via inhibiting CYP450 enzyme, promoting antioxidant pathway Nrf2/GST, activating antioxidant enzymes (SOD and GST), and regulating the mitochondrial pathway.
黄曲霉毒素B1（AFB1）通过其环氧化代谢产物AFBO引起氧化应激和肝细胞凋亡，AFBO由CYP450酶催化产生。阿魏酸（FA）是一种常见于植物中的酚酸，以其抗氧化能力而闻名。然而，FA在AFB1诱导的肝损伤中的作用仍不明确。在本研究中，将大鼠暴露于AFB1并同时用FA处理30天。结果表明：I）FA减轻了AFB1诱导的组织病理学变化，抑制了AFB1诱导的血清学指标升高，并减少了肝脏中AFBO的产生。II）FA显著降低了AFB1诱导的CYP450表达增加。FA与CYP2A6的分子对接结果显示出高拟合分数和相互作用。III）FA明显抑制了丙二醛（MDA）的产生，并显著激活了Nrf2/谷胱甘肽S-转移酶（GST）途径和抗氧化酶（超氧化物歧化酶（SOD）和GST）。IV）FA恢复了AFB1诱导的肝细胞凋亡、p53、bax、细胞色素c（cyt-c）、半胱天冬酶-9（caspase-9）、半胱天冬酶-3（caspase-3）的高表达以及bcl-2的低表达。从这些结果表明，FA通过抑制CYP450酶、促进抗氧化途径Nrf2/GST、激活抗氧化酶（SOD和GST）以及调节线粒体途径，对大鼠AFB1诱导的肝损伤具有显著效果。
