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Furfural Reverses the Toxicity of Ethanol by Maintaining NAD+-NADH Redox State and Mitochondrial Function
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  • Zhuo Cheng,
  • Xuanmei Luo,
  • Zixin Zhu,
  • Yonghui Huang,
  • Xiue Yan
Zhuo Cheng
Peking University Third Hospital

Corresponding Author:[email protected]

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Xuanmei Luo
Beijing Hospital
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Zixin Zhu
Guizhou Medical University
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Yonghui Huang
Peking University Third Hospital
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Xiue Yan
Peking University Third Hospital
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Abstract

Background and Purpose: Alcoholic liver disease (ALD), which is induced by alcohol intake, increases the health burden worldwide. However, there is still a lack of effective drugs preventing ALD. Furfural, a small molecule that is widespread in baked goods, can limit alcohol fermentation in the microorganism and may have the potential effect to reverse the toxicity of ethanol. Experimental Approach: Human HepG2 cells were incubated with ethanol and furfural, and cell viability and the NAD+-NADH ratio were tested. Using RNA-seq to annotate the enrichment pathway, then confirmed the pathways by RT-qPCR and Western blot. Mitochondrial function tests were performed. C57BL/6J mice were fed with the Lieber-DeCarli liquid diet. Biochemical analysis of serum and histology analysis of mice livers were performed after 4 weeks. Key Results: We found that a low dose of furfural restored cell viability damaged by ethanol, normalized NAD+-NADH ratio, and upgraded PI3K-Akt pathway expression. Different concentrations of furfural have different effects on the mitochondrion: a low dose of furfural could reduce ROS production, maintain the mitochondrial transmembrane potential, and inhibit the apoptosis pathway, while a high dose of furfural has a reversed effect. In mice, furfural could mitigate the transaminase elevation induced by ethanol, reverse the lipid metabolism disorder. Conclusions and Implications: Low dose of furfural could reduce the liver toxicity of ethanol. Having food containing furfural appropriately when drinking may be a convenient and useful way to prevent ALD.