Indole-3-Carbinol Derivative DIM Mitigates Carbon Tetrachloride-Induced Acute Liver Injury in Mice by Inhibiting Inflammatory Response, Apoptosis and Regulating Oxidative Stress

被引:46
作者
Munakarmi, Suvesh [1 ]
Chand, Lokendra [1 ]
Shin, Hyun Beak [2 ]
Jang, Kyu Yun [3 ]
Jeong, Yeon Jun [1 ,2 ]
机构
[1] Chonbuk Natl Univ, Med Sch, Biomed Res Inst, Lab Liver Regenerat, Jeonju 54907, South Korea
[2] Chonbuk Natl Univ Hosp, Dept Surg, Jeonju 54907, South Korea
[3] Chonbuk Natl Univ Hosp, Dept Pathol, Jeonju 54907, South Korea
关键词
DIM; carbon tetrachloride (CCl4); nuclear factor erythroid-2-related factor 2 (Nrf2); hemeoxygenase-1 (HO-1); inflammation; apoptosis; oxidative stress; NF-KAPPA-B; INDUCED HEPATOTOXICITY; ANTIOXIDANT RESPONSE; HEPATOCYTE APOPTOSIS; KUPFFER CELLS; IN-VITRO; PROTECTS; NRF2; ACTIVATION; 3,3'-DIINDOLYLMETHANE;
D O I
10.3390/ijms21062048
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
3,3 '-Diindolylmethane (DIM), a metabolic product of indole-3-carbinol extracted from cruciferous vegetables exhibits anti-inflammatory and anti-cancer properties. Earlier, the product has been demonstrated to possess anti-fibrotic properties; however, its protective effects on liver injury have not been clearly elucidated. In this study, we postulated the effects and molecular mechanisms of action of DIM on carbon tetrachloride (CCl4)-induced liver injury in mice. Acute liver injury was induced by a single intraperitoneal administration of CCl4 (1 ml/kg) into mice. DIM was injected via subcutaneous route for three days at various doses (2.5, 5 and 10 mg/kg) before CCl4 injection. Mice were sacrificed and serum was collected for quantification of serum transaminases. The liver was collected and weighed. Treatment with DIM significantly reduced serum transaminases levels (AST and ALT), tumor necrosis factor-alpha (TNF-alpha) and reactive oxygen species (ROS). CCl4- induced apoptosis was inhibited by DIM treatment by the reduction in the levels of cleaved caspase-3 and Bcl2 associated X protein (Bax). DIM treated mice significantly restored Cytochrome P450 2E1, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression in CCl4 treated mice. In addition, DIM downregulated overexpression of hepatic nuclear factor kappa B (NF-kappa B) and inhibited CCl4 mediated apoptosis. Our results suggest that the protective effects of DIM against CCl4- induced liver injury are due to the inhibition of ROS, reduction of pro-inflammatory mediators and apoptosis.
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页数:17
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