丁酸钠可减轻氟化钠诱导的大鼠肝毒性中的氧化应激、细胞凋亡和过度线粒体自噬。

Sodium butyrate attenuates oxidative stress, apoptosis, and excessive mitophagy in sodium fluoride-induced hepatotoxicity in rats.

作者信息

Xia Jing, Zhang Xiaolin, Xu Leiyu, Yan Nan, Sun Zhenxiang, Duan Xiaoxu, Meng Lu, Qi Rong, Ren Fu, Wang Zhengdong

机构信息

Liaoning Province Key Laboratory for phenomics of Human Ethnic Specificity and Critical Illness, Shenyang Medical College, Shengyang, PR China.

Department of General Surgery, Central Hospital Affiliated to Shenyang Medical College, Shengyang, PR China.

出版信息

Ecotoxicol Environ Saf. 2025 Feb;291:117821. doi: 10.1016/j.ecoenv.2025.117821. Epub 2025 Jan 30.

DOI:10.1016/j.ecoenv.2025.117821

PMID:39884013

Abstract

AIM

Long-term exposure to excess sodium fluoride (NaF) can cause chronic fluorosis. Liver, the most important detoxification organ, is the most vulnerable to the effects of fluoride. Sodium butyrate (NaB), a short-chain fatty acid produced in the intestinal tract, maintains normal mitochondrial function in vivo and reduces liver inflammation and oxidative stress. This study aims to investigate the protective effect and potential mechanism of NaB on liver injury in fluoride poisoned rats, particularly through the mitophagy pathway.

METHODS

Rats were randomly divided into four groups of 12 male rats each: control, NaF (100 mg/mL), NaB (1000 mg/kg), and NaF (100 mg/mL)+NaB (1000 mg/kg) group.

KEY FINDINGS

Changes in the levels of liver enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], and malondialdehyde [MDA]) confirmed NaF-induced liver injury. NaF also changed the levels of autophagy markers (Beclin-1, LC3α/β, P62), and increased the level of apoptosis. The combined use of NaB and NaF significantly ameliorated these indices.

SIGNIFICANCE

These findings indicate that NaB may provide effective protection against NaF-induced liver injury through its attenuates oxidative stress, apoptosis, and excessive mitophagy mechanisms.

摘要

目的

长期暴露于过量的氟化钠（NaF）会导致慢性氟中毒。肝脏作为最重要的解毒器官，最容易受到氟化物影响。丁酸钠（NaB）是肠道中产生的一种短链脂肪酸，可维持体内正常的线粒体功能，并减轻肝脏炎症和氧化应激。本研究旨在探讨NaB对氟中毒大鼠肝损伤的保护作用及潜在机制，特别是通过线粒体自噬途径。

方法

将大鼠随机分为四组，每组12只雄性大鼠：对照组、NaF（100 mg/mL）组、NaB（1000 mg/kg）组和NaF（100 mg/mL）+NaB（1000 mg/kg）组。

主要发现

肝酶（丙氨酸氨基转移酶[ALT]和天冬氨酸氨基转移酶[AST]）和抗氧化酶（超氧化物歧化酶[SOD]、过氧化氢酶[CAT]和丙二醛[MDA]）水平的变化证实了NaF诱导的肝损伤。NaF还改变了自噬标志物（Beclin-1、LC3α/β、P62）的水平，并增加了细胞凋亡水平。NaB与NaF联合使用显著改善了这些指标。