Nouri Ali, Ghatreh-Samani Keihan, Amini-Khoei Hossein, Najafi Mohammad, Heidarian Esfandiar
Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Medical Plant Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
J Biochem Mol Toxicol. 2023 Oct;37(10):e23427. doi: 10.1002/jbt.23427. Epub 2023 Jun 24.
Drug-induced liver injury is one of the main challenges that leads to the withdrawal of several drugs in the clinical setting. Cyclosporine is one of the drugs that its long-term administration exerts devastating effects on the hepatocytes. In the present study, we aimed to evaluate the effect of ferulic acid, a natural compound found in plants, on cyclosporine-mediated hepatotoxicity. Forty-eight male Wistar rats were treated with cyclosporine and/or ferulic acid to evaluate the function as well as the morphology of liver cells. We found that ferulic acid dose-dependently recovered the functional as well as histopathological parameters of liver cells, as revealed by the improvement of hepatocellular vacuolation, portal fibroplasia, and necrosis. Moreover, this phenolic compound was able to restore the balance of the redox system in cyclosporine-treated rats by activating the nuclear factor (NF) erythroid 2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1) signaling axis. Of note, the protective effects of ferulic acid against cyclosporine-mediated liver toxicity were not restricted only to induction of the potential antioxidant property, as in the presence of this agent, the expression of pro-inflammatory cytokines such as NF-κB, tumor necrosis factor (TNF)-α, and interleukin-1β was also diminished. Ferulic acid also shifted the equilibrium between the expression levels of proapoptotic to antiapoptotic proteins and thereby prevented the development of cyclosporine-induced liver injury. Overall, these findings highlighted that ferulic acid can reduce cyclosporine-induced liver injury due to its antioxidant properties.
药物性肝损伤是导致多种药物在临床中撤市的主要挑战之一。环孢素是其中一种长期使用会对肝细胞产生毁灭性影响的药物。在本研究中，我们旨在评估植物中发现的天然化合物阿魏酸对环孢素介导的肝毒性的影响。将48只雄性Wistar大鼠用环孢素和/或阿魏酸处理，以评估肝细胞的功能和形态。我们发现，阿魏酸呈剂量依赖性地恢复了肝细胞的功能以及组织病理学参数，肝细胞空泡化、门脉纤维化和坏死的改善表明了这一点。此外，这种酚类化合物能够通过激活核因子（NF）红系2相关因子2（Nrf2）/血红素加氧酶-1（HO-1）信号轴来恢复环孢素处理大鼠体内氧化还原系统的平衡。值得注意的是，阿魏酸对环孢素介导的肝毒性的保护作用不仅限于诱导潜在的抗氧化特性，因为在这种药物存在的情况下，促炎细胞因子如NF-κB、肿瘤坏死因子（TNF）-α和白细胞介素-1β的表达也会减少。阿魏酸还改变了促凋亡蛋白与抗凋亡蛋白表达水平之间的平衡，从而预防了环孢素诱导的肝损伤的发生。总体而言，这些发现突出表明，阿魏酸因其抗氧化特性可减轻环孢素诱导的肝损伤。
