WAN Tao, YAN Biao, HONG Liang. Role of phosphorylated extracellular signal-regulated kinase 1/2 in dibutyl phthalate-induced hepatic damage in male mice[J]. Journal of Environmental and Occupational Medicine, 2020, 37(6): 622-627. DOI: 10.13213/j.cnki.jeom.2020.19733
Citation: WAN Tao, YAN Biao, HONG Liang. Role of phosphorylated extracellular signal-regulated kinase 1/2 in dibutyl phthalate-induced hepatic damage in male mice[J]. Journal of Environmental and Occupational Medicine, 2020, 37(6): 622-627. DOI: 10.13213/j.cnki.jeom.2020.19733

Role of phosphorylated extracellular signal-regulated kinase 1/2 in dibutyl phthalate-induced hepatic damage in male mice

  • Background Dibutyl phthalate (DBP) has potential hepatotoxicity. The activated form of extracellular signal-regulated kinase (ERK1/2), phosphorylated ERK1/2 (p-ERK1/2), has been confirmed to be associated with liver injury. It is unclear whether DBP exposure can lead to hepatic damage through p-ERK1/2.
    Objective This study explores the role of p-ERK1/2 mediated by oxidative stress in DBP-induced hepatic damage in mice.
    Methods SPF male KM mice (n=28) were randomly divided into four groups:control group, 50 mg·kg-1·d-1 DBP group, 2.5 mg·kg-1·d-1 U0126 (a non-adenosine triphosphate competitive specific inhibitor of ERK1/2) group, and 50mg·kg-1·d-1 DBP+2.5 mg·kg-1·d-1 U0126 group. After 28 days of experiment, the organ coefficient of mice liver was measured; the liver pathological changes were observed after HE staining; the level of reactive oxygen species (ROS) in liver was detected with 2', 7'-dichlorodihydrofluorescein diacetate (DCFH-DA); the level of malondialdehyde (MDA) was detected by thiobarbituric acid colorimetric method; the total antioxidative capacity (T-AOC) was detected by chemical colorimetric assay; the expressions of ERK1/2 and p-ERK1/2 in liver tissues were detected by Western blotting; the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (ALB) in serum were determined with automatic biochemical analyzer.
    Results After 28 days of designed treatment, compared with the control group, the DBP group showed decreased liver organ coefficient(4.97±0.14)%, increased ALT/AST (2.02±0.25), decreased ALB level(18.54±2.64) U·L-1, increased fluorescence intensity of ROS (6 387.0±84.80), increased MDA level(1.65±0.10) μmol·g-1 (in protein), decreased T-AOC level(0.55±0.050) U·mg-1, and increased p-ERK1/2 protein expression level (1.29±0.02) (P < 0.05). After the U0126 treatment, compared with the DBP group, the DBP+U0126 group showed reversed effects, including increased liver organ coefficient(5.36±0.33)%, decreased ALT/AST (1.40±0.17), increased ALB level(28.92±0.69) U·L-1, decreased fluorescence intensity of ROS (5 934.8±38.07), decreased MDA level(1.10±0.08) μmol·g-1 (in protein), and decreased expression level of p-ERK1/2 (0.90 ±0.13) (P < 0.05).
    Conclusion DBP could increase the level of oxidative stress and up-regulate the expression of p-ERK1/2 protein in the liver tissues of male mice, resulting in liver dysfunction; while U0126 could repair the DBP-induced hepatic damage by inhibiting the phosphorylation of ERK1/2, suggesting that p-ERK1/2 is involved in the hepatic damage caused by DBP.
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