The deleterious effect of stress-induced depression on rat liver: Protective role of resveratrol and dimethyl fumarate via inhibiting the MAPK/ERK/JNK pathway.,Journal of Biochemical and Molecular Toxicology

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The deleterious effect of stress-induced depression on rat liver: Protective role of resveratrol and dimethyl fumarate via inhibiting the MAPK/ERK/JNK pathway.
Journal of Biochemical and Molecular Toxicology ( IF 3.2 ) Pub Date : 2020-09-09 , DOI: 10.1002/jbt.22627
Mona A Kortam ₁ , Bassam Mohamed Ali ₂ , Nevine Fathy ₁

Affiliation

This study aimed to uncover the protective potentiality of resveratrol and dimethyl fumarate (DMF) in the liver of a chronic unpredictable mild stress (CUMS)‐induced depression animal model. Resveratrol and DMF significantly alleviated CUMS‐induced behavioral abnormalities in stressed rats through improving sucrose preference in sucrose preference test and decreasing immobility time in a forced swimming test. They also mitigated serum corticosterone levels and elevated serum serotonin levels, which were formerly disturbed in CUMS rats. The hepatoprotective effect is evidenced by improvement in hepatic histopathological examinations, as well as normalized serum alanine aminotransferase and aspartate aminotransferase activities. Molecular signaling of resveratrol and DMF was estimated by diminishing hepatic expression of phosphorylated p38 mitogen‐activated protein kinase (MAPK), extracellular signal‐regulated kinase1/2 (ERK1/2), and c‐Jun N‐terminal kinase (JNK). Consequently, they improved the hepatic antioxidant and anti‐inflammatory activities as elaborated by the normalization of total antioxidant capacity, glutathione, malondialdehyde, nuclear factor‐κB, tumor necrosis factor‐α, and myeloperoxidase levels. In addition, they inhibited hepatocyte apoptosis as evidenced by the increased expression of B‐cell lymphoma 2, the decreased expression of Bax, as well as the suppressed activity of caspase‐3. In conclusion, resveratrol and DMF purveyed a significant anti‐depressant effect, which may be mediated, at least in part, via inhibiting the MAPK/ERK/JNK pathway in the CUMS rat model.

中文翻译：

应激性抑郁症对大鼠肝脏的有害影响：白藜芦醇和富马酸二甲酯通过抑制MAPK / ERK / JNK途径发挥保护作用。

这项研究旨在揭示白藜芦醇和富马酸二甲酯（DMF）在慢性不可预测的轻度应激（CUMS）诱发的抑郁动物模型肝脏中的保护潜力。白藜芦醇和DMF可通过改善蔗糖偏爱试验中的蔗糖偏爱和减少强迫游泳试验中的不动时间来显着缓解应激大鼠CUMS诱发的行为异常。他们还减轻了血清皮质酮水平和血清5-羟色胺水平的升高，这以前在CUMS大鼠中受到干扰。肝组织病理学检查的改善以及血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶活性的改善证明了其对肝脏的保护作用。白藜芦醇和DMF的分子信号传导是通过减少磷酸化的p38丝裂原活化蛋白激酶（MAPK），细胞外信号调节激酶1/2（ERK1 / 2）和c-Jun N末端激酶（JNK）的肝表达来估计的。因此，通过改善总抗氧化能力，谷胱甘肽，丙二醛，核因子κB，肿瘤坏死因子α和髓过氧化物酶水平的标准化，他们改善了肝脏的抗氧化和抗炎活性。此外，它们还抑制了肝细胞凋亡，这可以通过B细胞淋巴瘤2的表达增加，Bax的表达减少以及caspase-3的抑制来证明。总之，白藜芦醇和DMF具有显着的抗抑郁作用，这至少可以部分地介导，

更新日期：2020-09-09

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