Overconsumption of alcohol could lead to severe liver injury that connects with oxidative stress, apoptosis, and inflammatory response. Previously, we proved that p-coumaric acid prevents ethanol induced reproductive toxicity; however, p-coumaric acid (PCA) on ethanol mediated hepatotoxicity has not been examined yet. In our work, we sought to study the potential of PCA in contradiction of ethanol induced hepatoxicity which linking with MAPKs, apoptosis, oxidative stress, and Nrf2 signaling. Foremost, we found that PCA could protect ethanol induced both L-02 and HepG2 hepatic cells by inhibiting cytotoxicity, ROS production, mitochondrial depolarization, and nuclear fragmentation. Also, in vivo experiments showed that the ethanol increasing the lipid markers (TBARS, CD) and depletes the antioxidants thereby increased phosphorylation of JNK, ERK, and p38 in rat liver tissues. Interestingly, PCA treatments inhibit ethanol exposed lipid markers and depletion of antioxidants, which directs the inhibition of MAPKs activation in rat liver tissues. We also noticed that the PCA protected ethanol induced apoptosis and liver markers by inhibiting the expression of Bax, caspases; AST, ALT, ALS, and LDH in liver tissue. Overall, the ameliorative consequence of PCA on ethanol induced oxidative stress and apoptosis was achieved by suppressing the expression of CYP2E1 and overexpressing Nrf2 and its target protein HO-1 in rat liver tissue. As a result, PCA was marked to be an effective antioxidant with notable hepatoprotection by inhibiting MAPKs and apoptosis signaling via enhancing Nrf2 signaling.

过量饮酒可能导致严重的肝损伤，并伴有氧化应激，细胞凋亡和炎症反应。以前，我们证明了对香豆酸可以阻止乙醇诱导的生殖毒性。然而，对香豆酸（PCA）对乙醇介导的肝毒性的作用尚未得到研究。在我们的工作中，我们试图研究PCA与乙醇诱导的肝毒性（与MAPK，细胞凋亡，氧化应激和Nrf2信号传导相关）相矛盾的潜力。首先，我们发现PCA可以通过抑制细胞毒性，ROS产生，线粒体去极化和核碎裂来保护乙醇诱导的L-02和HepG2肝细胞。另外，体内实验表明，乙醇增加了脂质标记（TBARS，CD）并耗尽了抗氧化剂，从而增加了大鼠肝组织中JNK，ERK和p38的磷酸化。有趣的是，PCA治疗可抑制暴露于乙醇的脂质标记物和抗氧化剂的消耗，这直接抑制了大鼠肝组织中MAPKs的活化。我们还注意到PCA通过抑制Bax，胱天蛋白酶的表达来保护乙醇诱导的细胞凋亡和肝标志物。肝组织中的AST，ALT，ALS和LDH。总体而言，PCA对乙醇诱导的氧化应激和细胞凋亡的改善作用是通过抑制CYP2E1的表达并过表达Nrf2及其靶蛋白HO-1在大鼠肝组织中实现的。结果是，