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Comparison of hepatotoxicity and toxic mechanisms of matrine and oxymatrine using in vivo and in vitro models / 中国比较医学杂志
Chinese Journal of Comparative Medicine ; (6): 44-50, 2018.
Article in Chinese | WPRIM | ID: wpr-703250
ABSTRACT
Objective To compare the hepatotoxicity of matrine (MT) and oxymatrine (OMT) and explore the severity and characteristics of their toxicity, and to preliminarily elucidate their toxic mechanisms. Methods Liver cell line LO-2 cells were treated with acetaminophen (APAP), matrine and oxymatrine for 24 h, and the IC values, the contents of enzymes in the liver cells, the pathological changes, the contents of malondialdehyde (MDA) and glutathione (GSH) and the cell apoptosis rate were detected. In addition, adult zebrafish were treated with APAP, matrine and oxymatrine for 96 h, and the LC50 values, the pathological morphology of the liver cells, the contents of MDA and GSH and the apoptosis rate were detected. Meanwhile, the expression of oxidative stress-related gene, zgc 136383, and the apoptosis-related genes, EIF4EBP3 and zgc 123120, was also detected. Results Matrine and oxymatrine had toxic effects on liver cells in vitro. The IC50 value of matrine was 5. 3 mmol/L, and that of oxymatrine was > 19 mmol/L. The contents of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in the liver cells treated with matrine or oxymatrine were increased, and the cells appeared swollen, with an increase in the MDA level and a decrease in the GSH level. The cell apoptosis rate was also increased (P < 0. 05). Furthermore, matrine and oxymatrine had toxic effects on the zebrafish. The LC50 value of matrine was 0. 41 mmol/L, and that of oxymatrine was >3. 8 mmol/L. The hepatocytes of zebrafish treated with matrine and oxymatrine appeared vacuolization in a mild to moderate degree, with an increase of the MDA content and a decrease of the GSH content. The cell apoptosis rate was increased (P <0. 05 for all). Expression of the oxidative stress-related gene zgc 136383 (P < 0. 05) and the apoptosis-resistant gene EIF4EBP3 (P < 0. 05) was down-regulated by matrine, but that of the apoptosis-promoting gene zgc 123120 was up-regulated (P < 0. 05). Conclusions Results of the experiments using liver cells in vitro are consistent with those using the in vivo zebrafish model. Matrine (MT) and oxymatrine (OMT) both have hepatotoxicity, with similar toxic characteristics, and the toxicity of matrine is greater than oxymatrine. The mechanism of their hepatotoxicity is related with oxidative stress and cell apoptosis. Matrine reduces lipid transportation and activates oxidative stress reactions through down-regulation of gene zgc 136383. In addition, matrine induces apoptosis in the liver cells via up-regulation of the apoptosis-promoting gene zgc 123120 and down-regulation of the apoptosis-resistant gene EIF4EBP3.

Full text: Available Index: WPRIM (Western Pacific) Type of study: Prognostic study Language: Chinese Journal: Chinese Journal of Comparative Medicine Year: 2018 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Type of study: Prognostic study Language: Chinese Journal: Chinese Journal of Comparative Medicine Year: 2018 Type: Article