Zanamivir alleviates ethanol intoxication through activating catalase

IF 2.9 3区医学 Q2 TOXICOLOGY Toxicology letters Pub Date : 2025-04-01 Epub Date: 2025-02-21 DOI:10.1016/j.toxlet.2025.02.010

Zhanghui Guan , Dong Tian , Menghan Wang , Xinrui Meng , Jia Kang , Zhuozhou Hu , Haoxuan Xu , Xiaomei Ma , Tingting Jin , Xiaoshan Gao , Yixuan Zhang , Youquan Gu , Xiaohua Liu , Xinping Chen

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Abstract

Objectives

Acute alcohol intoxication is characterized as high morbidity and mortality. To explore new chemicals to relieve ethanol intoxication, we tried to explore the activators of catalase (CAT), an enzyme responsible for oxidization of ethanol into acetaldehyde to accelerate ethanol removal.

Methods

We identified zanamivir, an antiviral agent, activated CAT in vitro after screening of clinical chemicals. Then, female KunMing mice were administrated with a single dose of ethanol to induce acute alcoholism model. The behavioral changes were recorded, besides, the serum ethanol derivatives and redox- associated with indexes in mouse liver were detected.

Results

We observed that zanamivir augmented CAT activity to reduce blood ethanol concentration. Mechanically, zanamivir enhanced superoxide dismutase (SOD) activity and glutathione (GSH) amount, meanwhile it decreased the concentration of malondialdehyde (MDA), thereby mitigating oxidative damage induced by ethanol consumption. Accordingly, zanamivir relieved drunkenness in mouse ethanol intoxication model, and simultaneously suppressed aspartate transferase (AST), alanine transaminase (ALT) and lactic acid (LD) accumulation to protect hepatic function and tissue.

Significance

Collectively, our work suggests that zanamivir should be repurposed for countering alcohol intoxication in clinic.

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扎那米韦通过激活过氧化氢酶减轻乙醇中毒。

目的：急性酒精中毒的特点是高发病率和死亡率。为了探索缓解乙醇中毒的新化学物质，我们试图探索过氧化氢酶（CAT）的活化剂，过氧化氢酶是一种负责将乙醇氧化成乙醛以加速乙醇去除的酶。方法：通过临床化学物质筛选，鉴定抗病毒药物扎那米韦体外激活CAT。然后用单剂量乙醇诱导昆明雌性小鼠急性酒精中毒模型。记录小鼠行为学变化，检测小鼠血清乙醇衍生物及肝脏氧化还原相关指标。结果：我们观察到扎那米韦增强CAT活性，降低血中乙醇浓度。机械上，扎那米韦提高了超氧化物歧化酶（SOD）活性和谷胱甘肽（GSH）含量，同时降低了丙二醛（MDA）浓度，从而减轻了乙醇消耗引起的氧化损伤。由此可见，扎那米韦在缓解小鼠乙醇中毒模型醉酒的同时，抑制天冬氨酸转移酶（AST）、丙氨酸转氨酶（ALT）和乳酸（LD）积累，保护肝脏功能和组织。意义：总的来说，我们的工作表明，扎那米韦应该在临床上用于对抗酒精中毒。

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