Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

The Benzene-induced Hepatic Cytochrome P450 2E1 Expression and Activity are Reduced by Quercetin Administration in Mice

Author(s): Jambour-Shabestary Amir-Ata, Vardast Mohammad-Reza and Hassan Malekinejad*

Volume 30, Issue 9, 2024

Published on: 28 February, 2024

Page: [676 - 682] Pages: 7

DOI: 10.2174/0113816128285832240216120053

Price: $65

conference banner
Abstract

Background: Benzene as an environmental and industrial agent induces adverse effects that are mainly metabolism-dependent.

Objectives: Effects of Quercetin (QCN) on Benzene (BNZ)-induced changes in the hepatic Cytochrome P450 2E1 expression and activity were investigated.

Methods: Thirty-six adult male mice were divided into 6 groups (n = 6) and nominated as control, BNZ (exposed to BNZ: 30 ppm), QCN (received QCN: 50 mg/kg, orally), and the fourth, fifth and sixth groups were exposed to 30 ppm BNZ and received 10, 50 and 100 mg/kg QCN respectively, for 28 days. The microsomal subcellular fraction was isolated from the liver samples and the activity of CYP 2E1 was measured based on the hydroxylation rate of 4-nitrophenol. The hepatic activity of myeloperoxidase also was assessed. Total antioxidant capacity and nitric oxide contents of the liver were determined. Expression changes of CYP 2E1 at the mRNA level were examined by qPCR technique.

Results: QCN lowered significantly (p < 0.05) the BNZ-increased hepatic nitric oxide levels and restored the BNZ-reduced antioxidant capacity. The BNZ-elevated activity of myeloperoxidase was declined in QCN-received mice. QCN downregulated the expression and activity of hepatic CYP 2E1 in BNZ-exposed animals.

Conclusion: Our results suggest that QCN could be a novel hepatoprotective compound for BNZ-induced hepatotoxicities, which is attributed to its capability in the down-regulation of CYP 2E1 expression and activity.

Keywords: Hepatotoxicity, cytochrome P450 2E1, oxidative status, QCN, BNZ, myeloperoxidase.

« Previous Next »
[1]
D'Andrea MA, Reddy GK. Health risks associated with benzene exposure in children: A systematic review. Glob Pediatr Health 2018; 5: 2333794X18789275.
[http://dx.doi.org/10.1177/2333794X18789275]
[2]
Dere E, Ari F. Effect of benzene on liver functions in rats (Rattus norvegicus). Environ Monit Assess 2009; 154(1-4): 23-7.
[http://dx.doi.org/10.1007/s10661-008-0374-7] [PMID: 18566902]
[3]
Kotseva K, Popov T. Study of the cardiovascular effects of occupational exposure to organic solvents. Int Arch Occup Environ Health 1998; 71: S87-91.
[PMID: 9827890]
[4]
Amin MM, Rafiei N, Poursafa P, et al. Association of benzene exposure with insulin resistance, SOD, and MDA as markers of oxidative stress in children and adolescents. Environ Sci Pollut Res Int 2018; 25(34): 34046-52.
[http://dx.doi.org/10.1007/s11356-018-3354-7] [PMID: 30280344]
[5]
Snyder R, Hedli CC. An overview of benzene metabolism. Environ Health Perspect 1996; 104(Suppl 6): 1165-71.
[http://dx.doi.org/10.1289/ehp.961041165] [PMID: 9118888]
[6]
Badham HJ, Renaud SJ, Wan J, Winn LM. Benzene-initiated oxidative stress: Effects on embryonic signaling pathways. Chem Biol Interact 2010; 184(1-2): 218-21.
[http://dx.doi.org/10.1016/j.cbi.2009.11.005] [PMID: 19913523]
[7]
Valentine JL, Lee SST, Seaton MJ, et al. Reduction of benzene metabolism and toxicity in mice that lack CYP2E1 expression. Toxicol Appl Pharmacol 1996; 141(1): 205-13.
[http://dx.doi.org/10.1016/S0041-008X(96)80026-3] [PMID: 8917693]
[8]
Weaver-Guevara HM, Fitzgerald RW, Cote NA, Greenberg A. Cytochrome P450 can epoxidize an oxepin to a reactive 2,3-epoxyoxepin intermediate: Potential insights into metabolic ring-opening of benzene. Molecules 2020; 25(19): 4542.
[http://dx.doi.org/10.3390/molecules25194542] [PMID: 33023027]
[9]
Li Y, Yao J, Han C, et al. Quercetin, inflammation and immunity. Nutrients 2016; 8(3): 167.
[http://dx.doi.org/10.3390/nu8030167] [PMID: 26999194]
[10]
Surapaneni KM, Priya VV, Mallika J. Pioglitazone, quercetin and hydroxy citric acid effect on cytochrome P450 2E1 (CYP2E1) enzyme levels in experimentally induced non alcoholic steatohepatitis (NASH). Eur Rev Med Pharmacol Sci 2014; 18(18): 2736-41.
[PMID: 25317811]
[11]
Maksymchuk O, Shysh A, Rosohatska I, Chashchyn M. Quercetin prevents type 1 diabetic liver damage through inhibition of CYP2E1. Pharmacol Rep 2017; 69(6): 1386-92.
[http://dx.doi.org/10.1016/j.pharep.2017.05.020] [PMID: 29132096]
[12]
Golabi-Habashi N, Salimi A, Malekinejad H. Quercetin attenuated the Benzene-induced hemato- and hepatotoxicity in mice. Toxicol Rep 2021; 8: 1569-75.
[http://dx.doi.org/10.1016/j.toxrep.2021.08.001] [PMID: 34430219]
[13]
Abd El-Shakour A, El-Ebiarie AS, Ibrahim YH, Abdel Moneim AE, El-Mekawy AM. Effect of benzene on oxidative stress and the functions of liver and kidney in rats. J Environ Occup Health 2015; 4: 34-9.
[14]
Jacquot L, Pourie G, Buron G, Monnin J, Brand G. Effects of toluene inhalation exposure on olfactory functioning: Behavioral and histological assessment. Toxicol Lett 2006; 165(1): 57-65.
[http://dx.doi.org/10.1016/j.toxlet.2006.01.018] [PMID: 16567067]
[15]
Cuzzocrea S, Ianaro A, Wayman NS, et al. The cyclopentenone prostaglandin 15-deoxy-Δ12,14-PGJ2 attenuates the development of colon injury caused by dinitrobenzene sulphonic acid in the rat. Br J Pharmacol 2003; 138(4): 678-88.
[http://dx.doi.org/10.1038/sj.bjp.0705077] [PMID: 12598422]
[16]
Benzie IFF, Strain JJ. Ferric reducing/antioxidant power assay: Direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration. Methods Enzymol 1999; 299: 15-27.
[http://dx.doi.org/10.1016/S0076-6879(99)99005-5] [PMID: 9916193]
[17]
Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 1982; 126(1): 131-8.
[http://dx.doi.org/10.1016/0003-2697(82)90118-X] [PMID: 7181105]
[18]
Lowry O, Rosebrough N, Farr AL, Randall R. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193(1): 265-75.
[http://dx.doi.org/10.1016/S0021-9258(19)52451-6] [PMID: 14907713]
[19]
Rutten AAJJL, Falke HE, Catsburg JF, et al. Interlaboratory comparison of total cytochrome P-450 and protein determinations in rat liver microsomes. Arch Toxicol 1987; 61(1): 27-33.
[http://dx.doi.org/10.1007/BF00324544] [PMID: 3439870]
[20]
Koop DR. Hydroxylation of p-nitrophenol by rabbit ethanol-inducible cytochrome P-450 isozyme 3a. Mol Pharmacol 1986; 29(4): 399-404.
[PMID: 3702859]
[21]
Chomczynski P, Sacchi N. The single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction: Twenty-something years on. Nat Protoc 2006; 1(2): 581-5.
[http://dx.doi.org/10.1038/nprot.2006.83] [PMID: 17406285]
[22]
Geraldino BR, Nunes RFN, Gomes JB, et al. Analysis of benzene exposure in gas station workers using trans,trans-muconic acid. Int J Environ Res Public Health 2020; 17(15): 5295.
[http://dx.doi.org/10.3390/ijerph17155295] [PMID: 32717818]
[23]
Yang X, Lu Y, He F, et al. Benzene metabolite hydroquinone promotes DNA homologous recombination repair via the NF-κB pathway. Carcinogenesis 2019; 40(8): 1021-30.
[http://dx.doi.org/10.1093/carcin/bgy157] [PMID: 30770924]
[24]
Guo X, Zhong W, Chen Y, Zhang W, Ren J, Gao A. Benzene metabolites trigger pyroptosis and contribute to haematotoxicity via TET2 directly regulating the Aim2/Casp1 pathway. EBioMedicine 2019; 47: 578-89.
[http://dx.doi.org/10.1016/j.ebiom.2019.08.056] [PMID: 31474553]
[25]
Martínez-Rodríguez JL, Gutiérrez-Hernández R, Reyes-Estrada CA, Granados-López AJ, Arcos-Ortega T, López JA. Quantitative measurement of oxidative damage in erythrocytes as indicator in benzene intoxications. Toxicol Mech Methods 2018; 28(6): 450-60.
[http://dx.doi.org/10.1080/15376516.2018.1455786] [PMID: 29564940]
[26]
Jaeschke H. Reactive oxygen and mechanisms of inflammatory liver injury: Present concepts. J Gastroenterol Hepatol 2011; 26(s1): 173-9.
[http://dx.doi.org/10.1111/j.1440-1746.2010.06592.x] [PMID: 21199529]
[27]
Kato Y. Neutrophil myeloperoxidase and its substrates: Formation of specific markers and reactive compounds during inflammation. J Clin Biochem Nutr 2016; 58(2): 99-104.
[http://dx.doi.org/10.3164/jcbn.15-104] [PMID: 27013775]
[28]
Sharapova NV, Krasikov SI, Petrova AA, Boev VM. Risk assessment metabolic disorders by prolonged exposure to low doses of benzene. Sys Rev Pharm 2020; 11(6): 420-4.
[29]
Jena AB, Samal RR, Kumari K, et al. The benzene metabolite p-benzoquinone inhibits the catalytic activity of bovine liver catalase: A biophysical study. Int J Biol Macromol 2021; 167: 871-80.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.11.044] [PMID: 33181220]
[30]
Li T, Li F, Liu X, Liu J, Li D. Synergistic anti-inflammatory effects of quercetin and catechin via inhibiting activation of TLR4-MyD88-mediated NF-κB and MAPK signaling pathways. Phytother Res 2019; 33(3): 756-67.
[http://dx.doi.org/10.1002/ptr.6268] [PMID: 30637814]
[31]
Moalin M, Strijdonck GPF, Beckers M, et al. A planar conformation and the hydroxyl groups in the B and C rings play a pivotal role in the antioxidant capacity of quercetin and quercetin derivatives. Molecules 2011; 16(11): 9636-50.
[http://dx.doi.org/10.3390/molecules16119636] [PMID: 22105713]
[32]
Battelli MG, Polito L, Bortolotti M, Bolognesi A. Xanthine oxidoreductase-derived reactive species: Physiological and pathological effects. Oxid Med Cell Longev 2016; 2016: 1-8.
[http://dx.doi.org/10.1155/2016/3527579] [PMID: 26823950]
[33]
Boesch-Saadatmandi C, Loboda A, Wagner AE, et al. Effect of quercetin and its metabolites isorhamnetin and quercetin-3-glucuronide on inflammatory gene expression: Role of miR-155. J Nutr Biochem 2011; 22(3): 293-9.
[http://dx.doi.org/10.1016/j.jnutbio.2010.02.008] [PMID: 20579867]
[34]
Carrasco D, Carrasco C, Souza-Mello V, Sandoval C. Effectiveness of antioxidant treatments on cytochrome P450 2E1 (CYP2E1) activity after alcohol exposure in humans and in vitro models: A systematic review. Int J Food Prop 2021; 24(1): 1300-17.
[http://dx.doi.org/10.1080/10942912.2021.1961801]
[35]
Tang Y, Tian H, Shi Y, et al. Quercetin suppressed CYP2E1-dependent ethanol hepatotoxicity via depleting heme pool and releasing CO. Phytomedicine 2013; 20(8-9): 699-704.
[http://dx.doi.org/10.1016/j.phymed.2013.03.010] [PMID: 23583009]
[36]
Patel HB, Patel UD, Mathapati BS, Modi CM. Effect of piperine and quercetin alone or in combination with marbofloxacin on CYP3A37 and MDR1 mRNA expression levels in broiler chickens. Res Vet Sci 2019; 126: 178-83.
[http://dx.doi.org/10.1016/j.rvsc.2019.09.005] [PMID: 31539794]

Rights & Permissions Print Cite
Article Metrics
15
2
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy