Full Text:   <3661>

Summary:  <2303>

CLC number: R96

On-line Access: 2024-08-27

Received: 2023-10-17

Revision Accepted: 2024-05-08

Crosschecked: 2014-11-14

Cited: 14

Clicked: 9451

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Li-li JI

http://orcid.org/0000-0001-6159-2626

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2014 Vol.15 No.12 P.1039-1047

http://doi.org/10.1631/jzus.B1400104


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


Author(s):  Jia-qi Zhang1,2, Liang Shi1,2, 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; more

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


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, 2014, 15(12): 1039-1047.

@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",
volume="15",
number="12",
pages="1039-1047",
year="2014",
publisher="Zhejiang University Press & Springer",
doi="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
%V 15
%N 12
%P 1039-1047
%@ 1673-1581
%D 2014
%I Zhejiang University Press & Springer
%DOI 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
VL - 15
IS - 12
SP - 1039
EP - 1047
%@ 1673-1581
Y1 - 2014
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1400104


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%29&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

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

References

[1] Bae, S.H., Sung, S.H., Lee, H.E., 2012. Peroxiredoxin III and sulfiredoxin together protect mice from pyrazole-induced oxidative liver injury. Antioxid Redox Signal, 17(10):1351-1361. 


[2] Barone, E., Trombino, S., Cassano, R., 2009. Characterization of the S-denitrosylating activity of bilirubin. J Cell Mol Med, 13(8b):2365-2375. 


[3] Brambilla, D., Mancuso, C., Scuderi, M.R., 2008. The role of antioxidant supplement in immune system, neoplastic, and neurodegenerative disorders: a point of view for an assessment of the risk/benefit profile. Nutr J, 7(1):29


[4] Calabrese, V., Cornelius, C., Trovato-Salinaro, A., 2010. The hormetic role of dietary antioxidants in free radical-related diseases. Curr Pharm Des, 16(7):877-883. 


[5] Chen, P., Wang, Z., Zeng, L., 2012. Protective effects of salecan against carbon tetrachloride-induced acute liver injury in mice. J Appl Toxicol, 32(10):796-803. 


[6] Chirumbolo, S., 2010. The role of quercetin, flavonols and flavones in modulating inflammatory cell function. Inflamm Allergy Drug Targets, 9(4):263-285. 


[7] Cohen, J.I., Chen, X., Nagy, L.E., 2011. Redox signaling and the innate immune system in alcoholic liver disease. Antioxid Redox Signal, 15(2):523-534. 


[8] Cui, Y.M., Han, Y., Yang, X.B., 2014. Protective effects of quercetin and quercetin-5',8-disulfonate against carbon tetrachloride-caused oxidative liver injury in mice. Molecules, 19(1):291-305. 


[9] Dajas, F., 2012. Life or death: neuroprotective and anticancer effects of quercetin. J Ethnopharmacol, 143(2):383-396. 


[10] de David, C., Rodrigues, G., Bona, S., 2011. Role of quercetin in preventing thioacetamide-induced liver injury in rats. Toxicol Pathol, 39(6):949-957. 


[11] di Meo, F., Lemaur, V., Cornil, J., 2013. Free radical scavenging by natural polyphenols: atom versus electron transfer. J Phys Chem A, 117(10):2082-2092. 


[12] Domitrović, R., Jakovac, H., Marchesi, V.V., 2012. Differential hepatoprotective mechanisms of rutin and quercetin in CCl4-intoxicated BALB/cN mice. Acta Pharmacol Sin, 33(10):1260-1270. 


[13] Han, D., Hanawa, N., Saberi, B., 2006. Mechanisms of liver injury. III. Role of glutathione redox status in liver injury. Am J Physiol Gastrointest Liver Physiol, 291(1):G1-G7. 


[14] Hgberg, J., Larson, R.E., Kristoferson, A., 1974. NADPH-dependent reductase solubilized from microsomes by peroxidation and its activity. Biochem Biophys Res Commun, 56(3):836-842. 


[15] Hollman, P.H., Katan, M.B., 1999. Dietary flavonoids: intake, health effects and bioavailability. Food Chem Toxicol, 37(9-10):937-942. 


[16] Hong, I.H., Ji, H., Hwa, S.Y., 2011. The protective effect of ENA actimineral resource A on CCl4-induced liver injury in rats. Mar Biotechnol, 13(3):462-473. 


[17] Janbaz, K.H., Saeed, S.A., Gilani, A.H., 2004. Studies on the protective effects of caffeic acid and quercetin on chemical-induced hepatotoxicity in rodents. Phytomedicine, 11(5):424-430. 


[18] Ke, B., Shen, X.D., Zhang, Y., 2013. KEAP1-NRF2 complex in ischemia-induced hepatocellular damage of mouse liver transplants. J Hepatol, 59(6):1200-1207. 


[19] Kelly, G.S., 2011. Quercetin. Altern Med Rev, 16(2):172-194. 


[20] Kretzschmar, M., Klinger, W., 1990. The hepatic glutathione system-influences of xenobiotics. Exp Pathol, 38(3):145-164. 


[21] Liang, Q.N., Sheng, Y.C., Jiang, P., 2011. The difference of glutathione antioxidant system in newly weaned and young mice liver and its involvement in isoline-induced hepatotoxicity. Arch Toxicol, 85(10):1267-1279. 


[22] Liu, C.M., Zheng, Y.L., Lu, J., 2010. Quercetin protects rat liver against lead-induced oxidative stress and apoptosis. Environ Toxicol Pharmacol, 29(2):158-166. 


[23] Mancuso, C., Barone, E., 2009. The heme oxygenase/biliverdin reductase pathway in drug research and development. Curr Drug Metab, 10(6):579-594. 


[24] Mancuso, C., Barone, E., Guido, P., 2012. Inhibition of lipid peroxidation and protein oxidation by endogenous and exogenous antioxidants in rat brain microsomes in vitroNeurosci Lett, 518(2):101-105. 


[25] Morio, L.A., Chiu, H., Sprowles, K.A., 2001. Distinct roles of tumor necrosis factor-α and nitric oxide in acute liver injury induced by carbon tetrachloride in mice. Toxicol Appl Pharmacol, 172(1):44-51. 


[26] Muldoon, M.F., Kritchevsky, S.B., 1996. Flavonoids and heart disease. BMJ, 312(7029):458-459. 


[27] Park, E.J., Pezzuto, J.M., 2012. Flavonoids in cancer prevention. Anti-Cancer Agents Med Chem, 12(8):836-851. 


[28] Pascoal, A.C., Ehrenfried, C.A., Eberline, M.N., 2011. Free radical scavenging activity, determination of phenolic compounds and HPLC-DAD/ESI-MS profile of Campomanesia adamantium leaves. Nat Prod Commun, 6(7):969-972. 


[29] Ratziu, V., Zelber-Sagi, S., 2009. Pharmacologic therapy of non-alcoholic steatohepatitis. Clin Liver Dis, 13(4):667-688. 


[30] Rhee, S.G., Chae, H.Z., Kim, K., 2005. Peroxiredoxins: a historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling. Free Radic Biol Med, 38(12):1543-1552. 


[31] Sass, G., Barikbin, R., Tiegs, G., 2012. The multiple functions of heme oxygenase-1 in the liver. Z Gastroenterol, 50(1):34-40. 


[32] Vatsyayan, R., Chaudhary, P., Sharma, A., 2011. Role of 4-hydroxynonenal in epidermal growth factor receptor-mediated signaling in retinal pigment epithelial cells. Exp Eye Res, 92(2):147-154. 


[33] Vicente-Snchez, C., Egido, J., Snchez-Gonzlez, P.D., 2008. Effect of flavonoid quercetin on cadmium-induced hepatotoxicity. Food Chem Toxicol, 46(6):2279-2287. 


[34] Watson, W.H., Yang, X., Choi, Y.E., 2004. Thioredoxin and its role in toxicology. Toxicol Sci, 78(1):3-14. 


[35] Weber, L.W., Boll, M., Stampfl, A., 2003. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit Rev Toxicol, 33(2):105-136. 


[36] Williams, C.H., Arscott, L.D., Mller, S., 2000. Thioredoxin reductase: two modes of catalysis have evolved. Eur J Biochem, 267(20):6110-6117. 


[37] Wu, H., Chen, M., Fan, Y., 2012. Determination of rutin and quercetin in Chinese herbal medicine by ionic liquid-based pressurized liquid extraction-liquid chromatography-chemiluminescence detection. Talanta, 88:222-229. 


[38] Yang, C.S., Landau, J.M., Huang, M.T., 2001. Inhibition of carcinogenesis by dietary polyphenolic compounds. Ann Rev Nutr, 21(1):381-406. 


[39] Yang, Y.C., Lii, C.K., Lin, A.H., 2011. Induction of glutathione synthesis and heme oxygenase 1 by the flavonoids butein and phloretin is mediated through the ERK/Nrf2 pathway and protects against oxidative stress. Free Radic Biol Med, 51(11):2073-2081. 


[40] Young, R., Hayes, J.D., Brown, K., 2010. Peroxiredoxin gene expression signatures in liver reflect toxic insult. ASSAY Drug Dev Technol, 8(4):512-517. 


[41] Yousef, M.I., Omar, S.A., El-Guendi, M.I., 2010. Potential protective effects of quercetin and curcumin on paracetamol-induced hitological changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in rat. Food Chem Toxicol, 48(11):3246-3261. 


[42] Yuan, L., Kaplowitz, N., 2009. Glutathione in liver diseases and hepatotoxicity. Mol Aspects Med, 30(1-2):29-41. 


[43] Yuan, L.P., Chen, F.H., Ling, L., 2008. Protective effects of total flavonoids of Bidens bipinnata L. against carbon tetrachloride-induced liver fibrosis in rats. J Pharm Pharmacol, 60(10):1393-1402. 



Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE