Abstract
The flavonol quercetin shows a wide range of effects in biological systems. We investigated whether quercetin exerts its proposed antioxidant properties via the antioxidant enzyme system. Quercetin in a concentration range from 5 to 100 µM decreased manganese superoxide dismutase, glutathione peroxidase, and copper zinc superoxide dismutase mRNA expression levels each by 30–40% in rat hepatoma H4IIE cells. Catalase mRNA expression levels increased about 30% but only with the cytotoxic concentration of 100 µM. Despite the down-regulation of antioxidant enzyme mRNA expression quercetin treatment of cells induced only a mild oxidative stress. Pretreatment of H4IIE cells with quercetin even protected against an oxidative stress resulting from hydrogen peroxide exposure. In conclusion, the antioxidant capacity of quercetin was shown not to be due to the antioxidant enzyme system.
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References
Adlercreutz H (1995) Phytoestrogens: epidemiology and a possible role in cancer protection. Environ Health Perspect 103:103–112
Borenfreund E, Puerner JA (1985) Toxicity determined in vitro by morphological alterations and neutral red absorption. Toxicol Lett 24:119–124
Breinholt V, Lauridsen ST, Dragsted LO (1999) Differential effects of dietary flavonoids on drug metabolizing and antioxidant enzymes in female rat. Xenobiotica 29:1227–1240
Chance B, Sies H, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 59:527–605
Clerch LB, Massaro D (1990) Perinatal rat lung catalase gene expression: influence of corticosteroid and hyperoxia. Am J Physiol 260:L428–L433
Cowan DB, Weisel RD, Williams WG, Mickle DAG (1993) Identification of oxygen responsive elements in the 5'-flanking region of the human glutathione peroxidase gene. J Biol Chem 268:26904–26910
Darville MI, Ho YS, Eizirik DL (2000) NF-κB is required for cytokine induced manganese superoxide dismutase expression in insulin-producing cells. Endocrinology 141:153–162
Hertog MGL, Hollman PCH, Katan MB, Kromhout D (1993) Intake of potentially anti carcinogenic flavonoids and there determinants in adults in the Netherlands. Nutr Cancer 20:21–29
Hertog MGL, Kromhout D, Aravanis C, Blackburn H, Buzina R, Fidanza F, Giampaoli S, Jansen A, Menotti A, Nedeljikovic S, Pekkarinen M, Simic BS, Toshima H, Feskens EJM, Hollman PCH, Katan MB (1995) Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med 155:381–386
Ho YS, Howard AJ, Crapo JD (1991) Molecular structure of a functional rat gene for manganese-containing superoxide dismutase. Am J Respir Cell Mol Biol 4:2378–2386
Inal ME, Kahraman A, Köken T (2001) Beneficial effects of quercetin on oxidative stress induced by ultraviolet A. Clin Exp Dermatol 26:536–539
Musonda CA, Helsby N, Chipman JK (1997) Effects of quercetin on drug metabolizing enzymes and oxidation of 2′,7-dichlorofluorescin in HepG2 cells. Hum Exp Toxicol 16:700–708
National Toxicology Program (1992) NTP Technical report: toxicology and carcinogenesis studies of quercetin in F344 rats. NTP TR 409, NIH, publ no 93-147478
Negre-Salvagyre A, Salvagyre R (1992) Quercetin prevents the cytotoxicity of oxidized low-density lipoproteins by macrophages. Free Radic Biol Med 12:101–106
Rangan GK, Wang Y, Tay YC, Harris DCH (1999) Inhibition of NFκB activation with antioxidants is correlated with reduced cytokine transcription in PTC. Am J Physiol 277:F779–F789
Rogers RJ, Chesrown SE, Kuo S, Monnier JM, Nick HS (2000) Cytokine-inducible enhancer with promoter activity in both the rat and human manganese-superoxide dismutase genes. Biochem J 347:233–242
Röhrdanz E, Kahl R (1998) Alterations of antioxidant enzyme expression in response to hydrogen peroxide. Free Radic Biol Med 24:27–38
Röhrdanz E, Obertrifter B, Ohler S, Kahl R (2000) Influence of adriamycin and paraquat on antioxidant enzyme expression in primary rat hepatocytes. Arch Toxicol 74:231–237
Röhrdanz E, Ohler S, Tran-Thi Q-H, Kahl R (2002) The phytoestrogen daidzein affects the antioxidant enzyme system of rat hepatoma H4IIE cells. J Nutr 132:370–375
Seo SJ, Kim HAT, Cho G, Rho HM, Jung G (1996) Sp1 and C/EBP-related factor regulate the transcription of human Cu/ZnSOD gene. Gene 178:177–185
Sichel G, Corsaro C, Scalia M, Di Bilio AJ, Bonomo RP (1991) In vitro scavenger activity of some flavonoids and melanins against 02 -. Free Radic Biol Med 11:1–8
Yamashita N, Tanemura H, Kawanishi S (1999) Mechanism of oxidative DNA damage induced by quercetin in the presence of Cu II. Mutat Res 425:107–115
Yoshioka T, Homma T, Meyrick B, Takeda M, Moore-Jarett T, Kon V, Ichikawa I (1994) Oxidants induce transcriptional activation of manganese superoxide dismutase in glomerular cells. Kidney Int 46:405–413
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We thank Mrs Sandra Ohler for her excellent technical assistance. The experiments performed comply with German law.
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Röhrdanz, E., Bittner, A., Tran-Thi, QH. et al. The effect of quercetin on the mRNA expression of different antioxidant enzymes in hepatoma cells. Arch Toxicol 77, 506–510 (2003). https://doi.org/10.1007/s00204-003-0482-7
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DOI: https://doi.org/10.1007/s00204-003-0482-7