JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)

Therapeutic detoxification of quercetin against carbon tetrachloride-induced acute liver injury in mice and its mechanism

Author(s): Jia-qi Zhang^1;2, Liang Shi^1;2, Xi-ning Xu², Si-chong Huang², Bin Lu¹, Li-li Ji¹, Zheng-tao Wang¹
Affiliation(s): 1. MOE Key Laboratory for Standardization of Chinese Medicines and Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China;2. School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Corresponding email(s): lichenyue1307@126.com
Key Words: Hepatotoxicity, Oxidative stress, Peroxiredoxin (Prx), Nuclear factor erythroid 2-related factor 2 (Nrf2), TrxR, Trx, HO-1

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Jia-qi Zhang, Liang Shi, Xi-ning Xu, Si-chong Huang, Bin Lu, Li-li Ji, Zheng-tao Wang. Therapeutic detoxification of quercetin against carbon tetrachloride-induced acute liver injury in mice and its mechanism[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B1400104

@article{title="Therapeutic detoxification of quercetin against carbon tetrachloride-induced acute liver injury in mice and its mechanism",
author="Jia-qi Zhang, Liang Shi, Xi-ning Xu, Si-chong Huang, Bin Lu, Li-li Ji, Zheng-tao Wang",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B1400104"
}

%0 Journal Article
%T Therapeutic detoxification of quercetin against carbon tetrachloride-induced acute liver injury in mice and its mechanism
%A Jia-qi Zhang
%A Liang Shi
%A Xi-ning Xu
%A Si-chong Huang
%A Bin Lu
%A Li-li Ji
%A Zheng-tao Wang
%J Journal of Zhejiang University SCIENCE B
%P 1039-1047
%@ 1673-1581
%D in press
%I Zhejiang University Press & Springer
doi="https://doi.org/10.1631/jzus.B1400104"

TY - JOUR
T1 - Therapeutic detoxification of quercetin against carbon tetrachloride-induced acute liver injury in mice and its mechanism
A1 - Jia-qi Zhang
A1 - Liang Shi
A1 - Xi-ning Xu
A1 - Si-chong Huang
A1 - Bin Lu
A1 - Li-li Ji
A1 - Zheng-tao Wang
J0 - Journal of Zhejiang University Science B
SP - 1039
EP - 1047
%@ 1673-1581
Y1 - in press
PB - Zhejiang University Press & Springer
ER -
doi="https://doi.org/10.1631/jzus.B1400104"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: This study observes the therapeutic detoxification of quercetin, a well-known flavonoid, against carbon tetrachloride (CCl₄) induced acute liver injury in vivo and explores its mechanism. Quercetin decreased CCl₄-increased serum activities of alanine and aspartate aminotransferases (ALT/AST) when orally taken 30 min after CCl₄ intoxication. The results of a histological evaluation further evidenced the ability of quercetin to protect against CCl₄-induced liver injury. Quercetin decreased the CCl₄-increased malondialdehyde (MDA) and reduced the glutathione (GSH) amounts in the liver. It also reduced the enhanced immunohistochemical staining of the 4-hydroxynonenal (4-HNE) in the liver induced by CCl₄. peroxiredoxin (Prx) 1, 2, 3, 5, 6, thioredoxin reductase 1 and 2 (trxR"&ck%5B%5D=abstract&ck%5B%5D=keyword'>trxR1/2), thioredoxin 1 and 2 (trx1/2), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) all play critical roles in maintaining cellular redox homeostasis. Real-time polymerase chain reaction (PCR) results demonstrated that quercetin reversed the decreased mRNA expression of all those genes induced by CCl₄. In conclusion, our results demonstrate that quercetin ameliorates CCl₄-induced acute liver injury in vivo via alleviating oxidative stress injuries when orally taken after CCl₄ intoxication. This protection may be caused by the elevation of the antioxidant capacity induced by quercetin.

槲皮素对四氯化碳引起的小鼠急性肝损伤治疗作用及其机理

本研究旨在观察槲皮素对四氯化碳（CCl）诱导的肝损伤的治疗解毒作用及其机理。首次发现槲皮素对CCl4诱导的肝损伤有治疗作用，并且首次发现Prx和Trx家族参与其中。检测小鼠血清转氨酶含量，并检测肝组织中丙二醛（MDA）、谷胱甘肽（GSH）和4-羟基壬烯醛（4-HNE）含量，并用实时聚合酶链式反应（PCR）检测肝组织中Prx1-6、TrxR1/2、Trx1/2、Nrf2和HO-1的mRNA表达情况。 CCl4造模成功后口服槲皮素对其造成的急性肝损伤有治疗作用，给药组小鼠血清中的转氨酶与模型组相比均有显著下降，通过MDA和免疫组化分析其机理可能和保护氧化应激损伤有关，通过实时PCR分析发现CCl抑制了抗氧化酶Prx家族、TrxRd1、TrxRd2、Trx1、Trx2和Nrf2及其下游HO-1的基因表达，而槲皮素可以逆转CCl降低的这些基因的表达。
肝毒性；氧应激损伤；Prx；Nrf2；TrxRd；Trx；HO-1

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槲皮素对四氯化碳引起的小鼠急性肝损伤治疗作用及其机理

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References