CN-121971416-A - Application of 1-hydroxy-2-butanone in treating acute liver injury

Abstract

The invention discloses an application of 1-hydroxy-2-butanone in preparing medicines for treating acute liver injury, belongs to the technical field of medicines, and is particularly used for treating liver injury induced by acetaminophen. Experiments prove that the 1-hydroxy-2-butanone can obviously improve the survival rate of mice with liver injury induced by acetaminophen (APAP), obviously lighten the necrosis of liver tissues and the infiltration of neutrophils, and further proves that the treatment by adopting the 1-hydroxy-2-butanone can obviously reduce the liver function injury induced by APAP by reversing the oxidative stress level caused by APAP.

Inventors

• GAO YOUGUANG
• Yu Binmei
• SHI MENGLU
• LIN XIANZHONG
• LIN BO

Assignees

• 福建医科大学附属第一医院

Dates

Publication Date

20260505

Application Date

20260317

Claims (4)

1. Application of 1, 1-hydroxy-2-butanone in preparing medicines for treating acute liver injury.
2. 2. Use according to claim 1, characterized in that 1-hydroxy-2-butanone is the sole active ingredient of the medicament for the treatment of acute liver injury.
3. 3. The use according to claim 1, wherein the acute liver injury therapeutic agent comprises 1-hydroxy-2-butanone and pharmaceutically acceptable excipients.
4. 4. The use according to any one of claims 1 to 3, wherein the acute liver injury comprises acetaminophen-induced liver injury.

Description

Application of 1-hydroxy-2-butanone in treating acute liver injury Technical Field The invention belongs to the technical field of medicines, and particularly relates to application of 1-hydroxy-2-butanone in treating acute liver injury. Background The liver is the most important organ for metabolism of drugs in the human body, and most of the drugs are metabolized by the liver through various pathways and finally discharged outside the body. Drug-induced liver injury (DILI) refers to liver damage caused by drugs and their metabolites, and has become an important public health problem worldwide. DILI is the main causative agent of acute liver failure in the united states, accounting for over 50%, and its incidence also shows a continuing trend in china. Acetaminophen (APAP) is widely accepted as the most widely used over-the-counter antipyretic analgesic worldwide, with its safety at conventional doses, however, once taken in excess, APAP is converted to a highly risky hepatotoxic substance, leading to acute liver failure and even life threatening. APAP-induced liver injury (APAP-induced liver injury, AILI) is not only a serious public health problem, but also the most classical, most in-depth model in DILI research. Acetylcysteine (NAC) is the only clinically approved AILI antidote at present, and acts by supplementing GSH synthesis precursor through ①, neutralizing NAPQI, directly scavenging ROS by ②, relieving oxidative stress and the like. However, NAC efficacy is highly dependent on early dosing (within 8 hours after APAP intake) and its protective effect is significantly reduced for delayed visit patients. In addition, NAC oral formulations are poorly compliant due to the "rotten egg" off-flavor, and intravenous administration can trigger anaphylactic-like reactions (e.g., bronchospasm, hypotension) and, in severe cases, life threatening. These limitations highlight that a single targeted NAPQI detoxification strategy is insufficient to address clinical needs, especially for high risk populations that progress to acute liver failure. Therefore, developing new, efficient and broader therapeutic strategies has become a critical issue. Disclosure of Invention The invention aims to provide a novel application of 1-hydroxy-2-butanone, namely application of the novel application in treating acute liver injury. In order to achieve the above purpose, the invention adopts the following technical scheme: The invention aims to protect application of 1-hydroxy-2-butanone in preparing medicines for treating acute liver injury, which takes 1-hydroxy-2-butanone as an active ingredient in the medicines for treating acute liver injury. Further, 1-hydroxy-2-butanone has the unique advantages of strong activity and wide treatment time window in AILI treatment, and can be used as the only active ingredient of acute liver injury treatment drugs. Further, the acute liver injury treatment drug comprises 1-hydroxy-2-butanone and pharmaceutically acceptable auxiliary materials. Further, the acute liver injury includes acetaminophen-induced liver injury. The invention has the remarkable advantages that: 1-hydroxy-2-butanone is a small molecule compound that naturally occurs in a variety of fruits and fermented foods. Experiments prove that the 1-hydroxy-2-butanone can obviously improve the survival rate of mice with liver injury induced by APAP, obviously lighten the necrosis of liver tissues and the infiltration of neutrophils, and further proves that the treatment by adopting the 1-hydroxy-2-butanone is possible to obviously reduce the liver function injury induced by APAP by reversing the oxidative stress level caused by APAP. . Drawings FIG. 1 shows the protective potential of 1-hydroxy-2-butanone for APAP-induced hepatocyte injury in an in vitro experiment (A) and its dose-dependent relationship (B), and the toxicity test of 1-hydroxy-2-butanone in hepatocytes (C), and the therapeutic drug delivery effect of 1-hydroxy-2-butanone following APAP stimulation (D). FIG. 2 is a schematic representation of mice model AILI established in vivo (A), and survival analysis of 1-hydroxy-2-butanone with positive drug NAC treatment AILI (B), H & E staining of liver tissue sections (C), liver tissue necrosis area score (D) and liver tissue section TUNEL staining and scoring (E, F). FIG. 3 is a graph of Ly6G immunofluorescence of liver tissue sections treated with different doses of 1-hydroxy-2-butanone (A), liver tissue Ly6G quantification (B), MPO immunohistochemistry and quantification of liver tissue sections (C, D), serum AST and ALT levels (E, F) and serum TNF-. Alpha.and IL-1β levels (G, H) in vivo experiments. Detailed Description In order to make the contents of the present invention more easily understood, the technical scheme of the present invention will be further described with reference to the specific embodiments, but the present invention is not limited thereto. 1.1.1 Potential therapeutic Activity of 1-hydroxy-2-butanone