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Nicotinamide mononucleotide and protective application thereof in myocardial injury of antitumor drug

An anti-tumor drug and mononucleotide technology, which is applied in the field of nicotinamide mononucleotide and its protective application in anti-tumor drug myocardial injury, can solve the problems of research and development reports that have no therapeutic value of NMN myocardial injury, etc. Achieve the effect of improving the related characteristics of myocardial injury and low cost of raw materials

Pending Publication Date: 2021-07-23
TSINGHUA UNIV +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, there is no research and development report on the value of NMN in the treatment of myocardial injury caused by chemotherapy drugs.

Method used

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  • Nicotinamide mononucleotide and protective application thereof in myocardial injury of antitumor drug
  • Nicotinamide mononucleotide and protective application thereof in myocardial injury of antitumor drug
  • Nicotinamide mononucleotide and protective application thereof in myocardial injury of antitumor drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] Example 1. The protective effect of NMN on the injury of H9c2 cardiomyocytes caused by doxorubicin and its analogs

[0057] H9c2 cardiomyocytes were diluted with medium to 10 6 / ml of cell suspension, and inoculated in 96-well plates, adding 100 μL of cell suspension to each well, cultured for 24 hours, and then treated with drugs. Divided into blank control group (pure DMEM), model group 1 (5 μM DOX), model group 2 (5 μM EPI), positive control group (20 μM Dexra), 5 μM DOX+20 μM Dexra group, 5 μM DOX+NMN group (NMN 10 / 20 / 30 / 50 / 100μM), 5μM EPI+NMN group (give NMN 20μM). After culturing for 24 hours, CCK-8 cell viability was used to measure the absorbance at 450 nm using a microplate reader to calculate the cardiomyocyte activity. Cell status was observed by an inverted light microscope.

[0058] The result is as figure 1 As shown, compared with the control group cell activity of 106.7%, the 5 μM DOX model group cell activity was 46.0%, and the 5 μM EPI model group ...

Embodiment 2

[0060] Example 2, NMN reduces the impact of doxorubicin H9c2 cardiomyocyte lactate dehydrogenase (LDH) leakage

[0061] Each group (n=4) takes 10 for each sample 6 Cells were fully lysed, and the content of LDH in the cells was detected by the pyruvate method. The LDH in the cells of the control group was 100%. 1 μmol of pyruvate produced in the system was regarded as 1 unit, calculated per unit / mg protein. After culturing for 24 h, the LDH detection kit was used for determination. The results show( image 3 ) The leakage rate of LDH in different medication groups was significantly lower than that in the model group.

Embodiment 3

[0062] Example 3, NMN inhibits the influence of doxorubicin H9c2 cardiomyocyte lipid peroxidation level

[0063] Oxygen free radicals attack polyunsaturated fatty acids in biomembranes, triggering lipid peroxidation and thus generating the lipid peroxide malondialdehyde (MDA). MDA can be condensed with thiobarbituric acid (TBA) to form a red product with a maximum absorption peak at 532nm. Adopt the same treatment method as in Example 2, and after culturing for 24 hours, operate according to the instructions of the MDA detection kit. The results show( Figure 4 ), the MDA content in the myocardial injury model group was significantly higher than that in the control group, P<0.05. The DOX+NMN group was significantly lower than the model group, confirming that NMN can inhibit lipid peroxidation induced by reactive oxygen species.

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PUM

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Abstract

The invention belongs to the technical field of drugs for preventing and treating cardiac toxicity of chemotherapeutic drugs, and particularly relates to nicotinamide mononucleotide and protective application thereof in myocardial injury of an antitumor drug. The nicotinamide mononucleotide is converted into NAD <+> in a human body to play a physiological function, such as activating NAD <+> substrate dependent enzyme Sirtuins (histone deacetylase, also known as silencing regulatory protein), regulating cell survival and death, and maintaining an oxidation-reduction state. NMN is used as a substitute of Dex, and has a protective effect on myocardial injury caused by anthracycline chemotherapeutic drugs such as Dox, and the side effect of Dox in treating tumors is relieved.

Description

technical field [0001] The invention belongs to the technical field of drugs for preventing and treating cardiotoxicity of chemotherapeutic drugs, and specifically relates to nicotinamide mononucleotide and its protective application in myocardial injury caused by anti-tumor drugs. Background technique [0002] With the increasing incidence of cancer, the cycle and cumulative dosage of antineoplastic drugs including anthracycline chemotherapy drugs are increasing, and the adverse reactions of chemotherapy drugs are becoming more and more prominent. Among them, the harm caused by myocardial injury is the most concerned. Therefore, With regard to the new clinical needs and discipline trends of chemotherapy drugs for myocardial injury, the new discipline of oncology and cardiology has developed rapidly in recent years. Its purpose is how to evaluate, prevent and treat cardiovascular adverse reactions caused by chemotherapy drugs while ensuring the anti-tumor effect of chemother...

Claims

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Application Information

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IPC IPC(8): A61K31/706A61K45/06A61P9/00A61P35/00
CPCA61K31/706A61K45/06A61P9/00A61P35/00
Inventor 邢东明原阳邹林峰高远真李梦娇卢琦叶婷张钰坤刘振柳欣林张仁帅王超钟英杰
Owner TSINGHUA UNIV
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