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Application of disulfiram in preparing anti-liver cirrhosis or anti-liver fibrosis pharmaceuticals

An anti-fibrosis and liver fibrosis technology, applied in drug combination, microbiological determination/testing, digestive system, etc., can solve problems such as not revealing the anti-cirrhosis and anti-fibrosis effects of disulfiram

Inactive Publication Date: 2013-09-18
SHANGHAI INST OF ONCOLOGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0022] Disulfiram has no anti-cirrhosis and anti-fibrosis effects in the prior art

Method used

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  • Application of disulfiram in preparing anti-liver cirrhosis or anti-liver fibrosis pharmaceuticals
  • Application of disulfiram in preparing anti-liver cirrhosis or anti-liver fibrosis pharmaceuticals
  • Application of disulfiram in preparing anti-liver cirrhosis or anti-liver fibrosis pharmaceuticals

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Example 1: Establishment of rat liver fibrosis model

[0038] 1) Test material:

[0039] Disulfiram (DSF): purchased from Sigma-Aldrich company;

[0040] Carbon tetrachloride (CCL4) and olive oil: purchased from Sinopharm Chemical Reagent Co., Ltd.

[0041] 2) Control group: get 6 3-4 week male Sprague-Dawley (SD) rats, intraperitoneally inject 50% carbon tetrachloride (prepared with olive oil), injection amount 2ml / kg body weight, 2 times a week, a total of 8 Zhou, established rat liver fibrosis animal model.

[0042] 3) Administration group: get 5 male Sprague-Dawley (SD) rats of 3-4 weeks, CCl 4 Disulfiram was administered at the same time, and its amount was injected intraperitoneally at 8 mg / kg body weight, twice a week.

Embodiment 2

[0043] Example 2: Preparation of Serum and Liver Specimens

[0044] 1) Serum preparation: After 8 weeks, the rats were sacrificed. The blood was placed in a 4°C refrigerator overnight, and the next day, the supernatant was drawn and centrifuged at 3000 rpm for 20 minutes, the supernatant was carefully drawn, and frozen at -20°C.

[0045] 2) Liver treatment: the left liver lobe was cut and placed in a cryopreservation tube, immediately placed in liquid nitrogen, and then placed at -80°C for RNA extraction and cytokine determination. After the remaining liver was washed twice in PBS, it was put into a 50ml centrifuge tube and fixed with paraformaldehyde solution for paraffin sectioning.

Embodiment 3

[0046] Embodiment 3: detection of serum ALT and AST

[0047] Alanine aminotransferase (ALT) kit and aspartate aminotransferase (AST) kit were purchased from Shanghai Shensuo Youfu Medical Diagnostic Products Co., Ltd.

[0048] a) Take a 96-well plate, add 7.5 μl of rat serum respectively, and make three replicate wells for each sample. Then add 150 μl of the R-1 solution in the kit to the sample well, mix well and react for 5 minutes;

[0049] b) Add 50 μl of the R-2 solution in the kit and mix;

[0050] c) Measure the absorbance A1 at 340nm wavelength after 1 minute;

[0051] d) Measure the absorbance A2 at 340nm wavelength again after 4 minutes;

[0052] e) Calculation of rat serum ALT value:

[0053] ALT(U / L)=(A1-A2) / 4 minutes×207.5μl×1000 / (6.22×7.5μl×1cm)

[0054] see results Figure 1A with Figure 1B , these figures show that CCl 4 +DSF treatment group (i.e. administration group) serum ALT and AST levels will be significantly lower than CCl 4 The treatment group ...

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Abstract

The invention relates to an application of disulfiram in preparing pharmaceuticals for relieving hepatic injury and further relates to an application of the disulfiram in preparing anti-liver fibrosis, anti-liver cirrhosis or liver fat reducing pharmaceuticals. The invention also discloses a heptatic stellate cell external proliferation inhabitation function of the disulfiram. A specific brand-new pharmaceutical is provided for treating anti-liver fibrosis and anti-liver cirrhosis.

Description

technical field [0001] The invention relates to the pharmaceutical application of disulfiram, and also relates to the molecular biological mechanism of disulfiram. Background technique [0002] Liver cirrhosis is one of the common chronic diseases that seriously endanger human health. Liver fibrosis is the pathological basis of liver cirrhosis. Various etiologies (such as viral hepatitis, alcoholic liver disease, non-alcoholic liver disease, drug and chemical factor damage, etc.) can cause liver damage and inflammation, leading to liver fibrosis and eventually developing For cirrhosis of the liver. Liver fibrosis is the result of excessive deposition of extracellular matrix, and it is also the main intermediate link in the further development of liver cirrhosis. The activation and proliferation of hepatic stellate cells (Hepatic Stellate Cells, HSCs) is the central link in the formation of liver fibrosis. Under pathological conditions, HSCs are activated and lose their or...

Claims

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Application Information

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IPC IPC(8): A61K31/145A61P1/16C12Q1/02
Inventor 张志刚覃文新杨小妹
Owner SHANGHAI INST OF ONCOLOGY
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