【Animal Modeling】-Comparison of liver toxicity between matrine and oxymatrine in vitro and in vivo models

  Objective: To compare the liver toxicity of matrine (MT) and oxymatrine (OMT), study the severity and characteristics of their toxicity, and first clarify the mechanism of their toxicity?

  Method: Use paracetamol (acetaminophen, APAP)? After 24 hours, matrine and oxymatrine are processed in liver cells. Liver cell enzyme content? Type of disease? Have you detected the levels of malondialdehyde (MDA) and glutathione (GSH) and the rate of apoptosis? Treat zebrafish with acetaminophen, matrine and oxymatrine. 96 hours, LC50, pathological morphology of liver cells, detection of malondialdehyde and glutathione content, detection of cell apoptosis, and oxidative stress-related gene zgc: 136383? Apoptosis-related genes EIF4, EBP3 and zgc: 123120? The detected expression.

  Result: Matrine and oxymatrine are toxic to liver cells, the IC50 of matrine is 5.3 mmol/L and oxymatrine → 19 mmol/L? Matrine and oxymatrine treated liver cells have increased alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase content, hepatocyte swelling, increased malondialdehyde content, and glutathione Peptide reduction and increased apoptosis rate (P3.8 mmol/L? Matrine and oxymatrine treatment of zebrafish liver cells showed mild to moderate vacuoles, increased malondialdehyde content, increased apoptosis rate, and glutathione Glycine content decreased (P\u003c0.05)? Matrine down-regulated oxidative stress-related genes zgc: 136383 (P\u003c0.05) and anti-apoptotic genes EIF4BP3, Progene zgc: 123120 (P\u003c 0.05)?

  Conclusion: The results of the in vivo and in vitro models are consistent. Matrine and oxymatrine have hepatotoxicity, and their toxicity is similar. Mechanisms related to oxidative stress and apoptosis: matrine down-regulates the gene zgc: 136383 to reduce lipid transport and activates oxidative stress; matrine up-regulates the apoptosis-promoting gene zgc: 123120 and down-regulates the induction of the anti-apoptotic gene EIF4EBP3 Apoptosis of liver cells?