Application of adenosine and derivatives thereof in prevention and treatment of medicament-induced liver injury

A technology of drug-induced liver injury and adenosine derivatives, applied in the field of medicine, can solve the problems of difficulty in reducing the mortality rate of acute liver failure, inability to effectively prevent acute liver failure, etc.

Inactive Publication Date: 2013-07-10
NANJING UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, whether adenosine and its derivatives can protect drug-induced liver injury has not yet been reported
[0006] At present, there is no drug that can effectively and completely block the occurrence of liver injury, so it cannot effectively prevent acute liver failure caused by extensive liver cell necrosis, and the mortality rate of acute liver failure has been difficult to reduce

Method used

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  • Application of adenosine and derivatives thereof in prevention and treatment of medicament-induced liver injury
  • Application of adenosine and derivatives thereof in prevention and treatment of medicament-induced liver injury
  • Application of adenosine and derivatives thereof in prevention and treatment of medicament-induced liver injury

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] (1) Animal model

[0038] The experimental animals were eight-week-old male C57BL / 6 (WT) mice. Raised under standard experimental conditions: 12-hour light-12-hour dark cycle, free access to water and food. APAP is used to establish a mouse model of acute liver failure, and APAP (300mg / kg) is administered by intragastric administration. WT mice were randomly divided into three groups. The first group was the control group (Saline), which was treated with the corresponding drug medium (normal saline) during the experiment; the second group was the APAP group (APAP), and APAP was administered intragastrically; The group was the adenosine treatment group (Ado+APAP), Adenosine (1.5mmol / kg) and APAP were mixed as a mixed solution for intragastric administration. After APAP gavage for 24 hours, blood and liver were collected for evaluation of liver injury.

[0039] (2) Determination of serum enzyme activity

[0040] After the whole blood was collected, it was naturally co...

Embodiment 2

[0055] (1) Animal model

[0056] The experimental animals were eight-week-old male C57BL / 6 (WT) mice. Raised under standard experimental conditions: 12-hour light-12-hour dark cycle, free access to water and food. APAP is used to establish a mouse model of acute liver failure, and APAP (300mg / kg) is administered by intragastric administration. WT mice were randomly divided into three groups. The first group was the control group (Saline), which was treated with the corresponding drug medium (normal saline) during the experiment; the second group was the APAP group (APAP), and APAP was administered intragastrically; The group was adenosine monophosphate treatment group (AMP+APAP), and AMP (3mmol / kg) and APAP were mixed as a mixed solution for intragastric administration. After APAP gavage for 24 hours, blood and liver were collected for evaluation of liver injury.

[0057] (2) Determination of serum enzyme activity

[0058] After the whole blood was collected, it was natura...

Embodiment 3

[0073] (1) Animal model

[0074]The experimental animals were eight-week-old male C57BL / 6 (WT) mice. Raised under standard experimental conditions: 12-hour light-12-hour dark cycle, free access to water and food. APAP is used to establish a mouse model of acute liver failure, and APAP (300mg / kg) is administered by intragastric administration. WT mice were randomly divided into four groups. The first group was the control group (Saline), which was treated with the corresponding drug medium (normal saline) during the experiment; the second group was the APAP group (APAP), and APAP was administered intragastrically; Adenosine treatment group (Ado+APAP) was divided into group Ⅲa and group Ⅲb. Group Ⅲa administered Adenosine (0.1mmol / kg) and APAP as a mixed solution orally, and group Ⅲb administered Adenosine (5mmol / kg ) mixed with APAP for intragastric administration; the fourth group is adenosine monophosphate treatment group (AMP+APAP), and is divided into Ⅳa group and Ⅳb grou...

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Abstract

The invention discloses application of adenosine and derivatives thereof in prevention and treatment of medicament-induced liver injury, relating to application of adenosine and derivatives thereof such as adenosine monophosphate, adenosine diphosphate and adenosine triphosphate in protection of acetaminophen-induced liver injury. A mouse model adopted in the application is an acetaminophen-induced mouse acute hepatic failure model, the dosage of the adenosine or derivatives thereof is 0.1 to 5mmol/kg, and the adenosine and derivatives thereof can reduce the activities of aspartate aminotransferase (AST) and alanine transaminase (ALT) in the medicament-induced liver injury, reduce the substantial cell necrosis area and improve the glutathione level so as to prevent and treat the acetaminophen-induced liver injury caused by liver toxic medicaments. Animal experiments prove that the adenosine and derivatives thereof have a significant effect on preventing and treating the medicament-induced liver injury, so the adenosine and derivatives thereof can be used for the preventing and treating processes of the medicament-induced liver injury, and a new method and means are provided for clinically treating the medicament-induced liver injury.

Description

technical field [0001] The invention belongs to the technical field of medicine, in particular to the application of adenosine and its derivatives in the prevention and treatment of drug-induced liver injury. Background technique [0002] The liver is one of the important organs in mammals. It is also called "processing plant" because of its functions of synthesis, detoxification, metabolism, secretion, biotransformation and immune defense. When severe damage is caused by various factors (such as viruses, alcohol, drugs, etc.), a large amount of necrosis of liver cells is caused, resulting in serious impairment or decompensation of the above-mentioned functions, and then the coagulation mechanism disorder and jaundice, hepatic encephalopathy, ascites A group of clinical syndromes mainly manifested as liver failure. [0003] In recent years, with the development and clinical promotion of a large number of new drugs, the incidence of drug-induced liver injury, especially acut...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/7076A61P1/16
CPCA61K31/7076A61P1/16
Inventor 张建法詹亦贝杨萍杨潇
Owner NANJING UNIV OF SCI & TECH
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