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Application of endogenous small molecular substances to rapid detection of early cardiotoxicity

A technology of small molecular substances and cardiotoxicity, which is applied in the direction of material inspection products, testing of pharmaceutical preparations, etc.

Active Publication Date: 2015-01-21
TIANJIN UNIV OF TRADITIONAL CHINESE MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the current clinical testing, lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase isoenzyme (CK-MB) are often used as the detection indicators of cardiotoxicity, but the current evaluation methods are limited in detection sensitivity. As well as the easy to cause false positive results, etc. need to be improved

Method used

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  • Application of endogenous small molecular substances to rapid detection of early cardiotoxicity
  • Application of endogenous small molecular substances to rapid detection of early cardiotoxicity
  • Application of endogenous small molecular substances to rapid detection of early cardiotoxicity

Examples

Experimental program
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Effect test

Embodiment 1

[0028] 1. Reagents: Acetonitrile was purchased from Oceanpak (Gothenburg, Sweden), and formic acid was purchased from ROE (USA), both of analytical grade. Purified water was purchased from Wahaha Company (Hangzhou, China). Normal saline was purchased from Qidu Pharmaceutical Co., Ltd. (Shandong, China). Doxorubicin (DOX), isoproterenol (ISO), 5-fluorouracil (5-FU), gentamicin, etimicin, Bupleurum and carbon tetrachloride were purchased from Silan Technology Co., Ltd. (China Tianjin), respectively dissolved in saline.

[0029] 2. Animal experiments: Animal experiments were conducted at the Institute of Biomedical Engineering, Chinese Academy of Medical Sciences (Tianjin, China). 140 male Wistar rats (200 ± 20 g) were maintained in an SPF grade laboratory. After the rats were purchased, they were reared under controlled environmental conditions of 12 hours of day and night alternation, an ambient temperature of 25±1° C., and an ambient humidity of 50±5%. After a week of adap...

Embodiment 2

[0037] The present invention further discloses a screening method for early biomarkers of cardiotoxicity based on metabolomics technology combined with SVM, including sample pretreatment, data collection, data processing (multivariate statistical analysis), specificity investigation of biomarkers, and exclusive biomarkers verification and optimization steps. It is characterized in that: gradient elution conditions are used in data collection: 0-0.5 min, A: 99%-99%; 0.5-2 min, A: 99%-50%; 2-9 min, A: 50% -1%; 9-10 min, A: 1%-1%; 10-10.5 min, A: 1%-99%; 10.5-12 min, A: 99%-99%, where mobile phase A refers to 0.1% Formic acid in water, mobile phase B refers to 0.1% formic acid in acetonitrile; MATLAB R2010a software (USA) was used in the verification and optimization of exclusive biomarkers to establish an SVM prediction model based on early biomarkers of cardiotoxicity, the process is as follows: biomarkers The peak area of ​​the drug in the normal saline group and each drug gr...

Embodiment 3

[0039] Practical application:

[0040] We thawed the collected serum at room temperature for detection of lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase isoenzyme (CK-MB) in serum. The results showed that 1 day after DOX administration, 3 days after ISO administration, and 3 days after 5-FU administration were significantly higher than those in the blank group (p Image 6 . Analyzing the results, we found that after 1 day of DOX administration, 3 days of ISO administration, and 3 days of 5-FU administration, the body was exposed to cardiotoxicity. Administration 1d, 2d cardiotoxicity has not been exposed. We considered that 1 day of DOX administration, 3 days of ISO administration, and 3 days of 5-FU administration were the toxic exposure periods. In addition, such as DOX administration for 6h, ISO administration for 12h, and 5-FU administration for 1d group, such toxic effects are occurring but the existing detection methods have not been able to...

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Abstract

The invention discloses an application of endogenous small molecular substances to rapid detection of early cardiotoxicity, wherein the endogenous small molecular substances refers to nine early cardiotoxicity biomarkers: L-carnitine, L-tryptophan, L-palmitoyl carnitine, 19-hydroxyl deoxycorticosterone, cholic acid, lysophosphatidyl choline (14: 0), lysophosphatidyl choline (22: 6), lysophosphatidyl choline (20: 2) and lysophosphatidyl choline (16: 0), and also refers to four early cardiotoxicity exclusive biomarkers: L-carnitine, 19-hydroxyl deoxycorticosterone, lysophosphatidyl choline (14: 0) and lysophosphatidyl choline (20: 2). According to the application of the endogenous small molecular substances to the rapid detection of the early cardiotoxicity, the screened early cardiotoxicity biomarkers are capable of giving rapid alarms to the toxicity before the heart tissues suffer pathological damages, so that the toxicity discovery time is early than the conventional biochemical detection indexes, more flexible judgement is carried out on the drug toxicity and diseases, and more time is provided for the early discovery and early treatment of the clinic cardiotoxicity.

Description

technical field [0001] The present invention involves using metabolomics technology to find early biomarkers of cardiotoxicity, then conducting specific investigations on them, and then using support vector machines (SVM) to validate and optimize them. More specifically, the application of endogenous small molecule substances in the rapid detection of early cardiotoxicity. Background technique [0002] Drug cardiotoxicity has been paid attention to due to its acute onset, great harm, and difficulty in recovery. It is reported that as many as 8.7% of the currently marketed drugs have been withdrawn due to their susceptibility to cardiotoxicity. Therefore, the detection and prevention of drug cardiotoxicity is particularly important. There is a certain period of time between the drug entering the body and the toxic exposure. How to use the existing technology to detect drug toxicity earlier is the significance of early prediction. In the current clinical testing, lactate de...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/15
Inventor 李遇伯张艳军局亮
Owner TIANJIN UNIV OF TRADITIONAL CHINESE MEDICINE
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