Application of disulfiram and dronedarone hydrochloride in preparation of medicine for relieving liver injury
Through the combined treatment method of disulfiram and donedaron hydrochloride, liver dysfunction and liver damage caused by amiodarone drugs were solved, which significantly alleviated hepatocyte death and liver function damage, and provided an effective response to reduce the damage of the drug to the liver.
Patent Information
- Application Number
- CN202510249402.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-03-04
- Publication Date
- 2025-04-25
AI Technical Summary
Amiodarone drugs such as donedaron hydrochloride often cause liver dysfunction and liver damage during use, limiting their promotion and use as antiarrhythmic drugs.
Using a combined treatment method of disulfiram and donedaron hydrochloride, it was verified through cell and animal experiments that it can effectively alleviate drug-induced liver damage.
In cell and animal experiments, the combined treatment of disulfiram and dronedarone hydrochloride significantly alleviated hepatocyte death and liver function damage, providing an effective response to reduce the damage of the drug to the liver.
Smart Images
Figure CN119868323A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the field of medicine, and in particular to a new use of disulfiram, specifically to the use of disulfiram and dronedarone hydrochloride in the preparation of a drug for alleviating liver damage. Background Art
[0002] Dronedarone hydrochloride (DH) is a common amiodarone-like antiarrhythmic drug used to treat atrial fibrillation and atrial flutter. With the continuous reporting of cases of acute liver injury, the potential impact of DH on liver function has led the European Medicines Agency (EMA) to issue a warning and require monthly liver function tests in the first 6 months of treatment, followed by a reduction in the frequency of use. Expert recommendations for the clinical application of DH in China mention the need for long-term monitoring of liver function during medication. Therefore, abnormal liver function and liver damage are common side effects during the use of DH, which also limits the promotion and use of DH as an antiarrhythmic drug. Finding out the causes of liver function damage caused by DH and targeting this link are important research directions for inhibiting the side effects of DH and promoting the promotion and application of DH drugs. Summary of the invention
[0003] Liver damage or abnormal liver function is a common liver-related side effect of dronedarone hydrochloride (DH) or other amiodarone drugs. The emergence of this side effect has greatly limited the clinical application of DH and other conventional antiarrhythmic drugs. However, there is currently a lack of research on the relevant mechanism of liver damage caused by this drug, and there is a lack of corresponding countermeasures to alleviate the liver damage side effect of this type of drug.
[0004] In view of this, the technical solution adopted by the present invention is: use of disulfiram in the preparation of drugs for alleviating liver damage.
[0005] Furthermore, the liver injury is acute liver injury induced by drugs, and the drug is dronedarone hydrochloride.
[0006] The present invention also provides the use of disulfiram and dronedarone hydrochloride in preparing a drug for alleviating liver damage.
[0007] Furthermore, the mass ratio of dronedarone hydrochloride to disulfiram is 32-80:1.
[0008] Because dronedarone hydrochloride (DH) is a common antiarrhythmic drug, and DH can affect liver function, the present invention finally provides the use of disulfiram and dronedarone hydrochloride in the preparation of antiarrhythmic drugs, wherein the disulfiram alleviates the liver damage induced by dronedarone hydrochloride.
[0009] The present invention innovatively adopts the method of DSF combined with DH treatment, which has a good effect of alleviating DH-induced liver cell death and liver function damage at both the cell and animal levels. Cell experiments using the liver cell line HuH-7 verified that DSF combined with DH treatment can significantly alleviate liver cell death caused by DH. Animal experiments on C57bl / 6j male mice showed that DSF also alleviated DH-induced liver function damage. BRIEF DESCRIPTION OF THE DRAWINGS
[0010] Figure 1 This is a flowchart of cell experiment operation;
[0011] Figure 2 This is a flowchart of animal experiment operation;
[0012] Figure 3 PI staining and analysis results;
[0013] Figure 4 Results of serum liver function indexes of mice;
[0014] Figure 5 TUNEL staining and statistical results of mouse liver tissue sections. DETAILED DESCRIPTION
[0015] Example 1, cell experiment, the experimental operation steps are as follows Figure 1 As shown. The liver cell line HuH-7 cells (5X10 5 Cells) were inoculated in a 12-well plate and left overnight for 12 hours for the cells to adhere to the wall. The 12-well plate was divided into four groups, with 3 sub-wells in each group. The four groups were: control group (CTRL), DH treatment group (40μM dronedarone hydrochloride treatment), DSF treatment group (1μM or 2.5μM disulfiram treatment), DSF+DH treatment group (40μM dronedarone hydrochloride + 1μM or 2.5μM disulfiram treatment). Drugs were added to the four groups according to different treatment methods, and PI propidium iodide (500nM) was added to each well after 12 hours. The cells were immediately photographed under a fluorescence microscope, and the cell morphology and number were captured in the bright field, and the PI staining was captured under a fluorescence (493 / 636nm) microscope.
[0016] Experimental results: Figure 3 , PI staining and analysis results showed that the situation of PI-positive dead liver cells was significantly aggravated after DH treatment, but the cell death was significantly alleviated after DSF combined with DH treatment. This result shows that DSF combined with DH treatment can significantly alleviate the liver cell death caused by DH.
[0017] Example 2, animal experiment, the experimental operation steps are as follows Figure 2As shown. C57bl / 6j male mice aged 8 weeks were divided into three groups, each with 10 mice. The three groups were respectively a control solvent treatment group, a DH treatment group (200mg / kg dronedarone hydrochloride treatment group), and a DSF+DH treatment group (200mg / kg DH+4mg / kg DSF treatment group). The administration method was daily gavage. After 22 days, the mice were blood drawn, euthanized, photographed, and the mouse liver tissue was collected. The liver function of the mice was detected by a blood biochemical detector, and the dead cells on the mouse liver sections were detected by a TUNEL dead cell detection kit, and photographed and recorded by a microscope.
[0018] Experimental results:
[0019] The liver function tests were performed on the sera of mice treated with different drugs, such as Figure 4 As shown in the results, the liver function-related enzymes AST, ALT and LDH of mice after oral administration of DH increased significantly, but the liver function indicators of mice after oral administration of DSF were significantly improved. This result shows that DSF also alleviated the liver function damage induced by DH in animal experiments.
[0020] After tissue sectioning, the death cell fluorescent staining kit was used to detect the death of liver cells. Figure 5 As shown, the number of dead cells in the liver sections of mice treated with DSF combined with DH was significantly lower than that after DH treatment alone, further illustrating the protective effect of DSF against DH-induced liver cell death.
Claims
1. Application of disulfiram in the preparation of drugs for alleviating liver damage.
2. The application according to claim 1, characterized in that: The liver injury is drug-induced acute liver injury.
3. The application according to claim 2, characterized in that: The drug is dronedarone hydrochloride.
4. Application of disulfiram and dronedarone hydrochloride in the preparation of drugs for alleviating liver damage.
5. The application according to claim 4, characterized in that: The mass ratio of dronedarone hydrochloride to disulfiram is 32-80:
1.
6. Use of disulfiram and dronedarone hydrochloride in the preparation of antiarrhythmic drugs, characterized in that: The disulfiram alleviates the liver injury induced by dronedarone hydrochloride.