Advances in Clinical and Experimental Medicine
2017, vol. 26, nr 2, March-April, p. 215–221
Publication type: original article
The role of 17β-estradiol metabolites in chromium-induced oxidative stress
1 Department of Toxicology, Wroclaw Medical University, Poland
Background. The increasing incidence of estrogen-dependent breast cancer and the presence in the environment of a large number of factors that interact with estrogen receptors have sparked interest in chemical influences on estrogen-dependent processes. In a previous work, the authors examined the interaction of estradiol with chromium. In the present article the importance of estradiol biotransformation in these interactions is investigated. There is no information in the available literature about the role of metabolites in exposure to chromium. It seems important because estradiol metabolites have various carcinogenic abilities and their formation during biotransformation could be increased or decreased by environmental enzyme inducers or inhibitors. The metabolites could play a detoxifying role or create a toxic synergism in free radical processes induced by chromium VI (CrVI).
Objectives. The aim of this study was to evaluate the influence of 2 17β-estradiol metabolites – 4-hydroxyestradiol (4-OHE2) and 16α-hydroxyestrone (16α-OHE1) – in conditions of oxidative stress caused by CrVI.
Material and Methods. Human blood, erythrocytes or mitochondria isolated from human placentas after natural deliveries were used in the experiments. The influence of CrVI, 4-OHE2 and 16-OHE1 on thiobarbituric acid reactive substances (TBARS), the hydroxyl radical (•OH), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione-S-transferase (GST), and the interactions of the metabolites exposed to chromium expressed by these factors were examined.
Results. 4-OHE2 reduced the level of TBARS induced by CrVI in mitochondria (p < 0.05) and in erythrocytes (p < 0.05), and increased SOD activity (p < 0.05). 16α-OHE1 increased the activity of GST in erythrocytes exposed to CrVI (p < 0.05).
Conclusion. The metabolites do not have toxic interactions with CrVI. On the contrary, they exhibited a protective effect. The mechanism of protection varied: 4-OHE2 decreased TBARS and increased SOD activity, while 16α-OHE1 increased GST activity.
oxidative stress, interactions, chromium VI, 4-hydroxyestradiol, 16α-hydroxyestrone
- Byrne C, Divekar SD, Storchan GB, Parodi DA, Martin MB. Metals and breast cancer. J Mammary Gland Biol Neoplasia. 2013;18:63–73.
- Mishra AK, Mohanty B. Effect of sublethal hexavalent chromium exposure on the pituitary-ovarian axis of a teleost, channapunctatus (bloch). Environ Toxicol. 2010;27:415–422.
- Rembacz K, Sawicka E, Długosz A. Role of estradiol in chromium–induced oxidative stress. Acta Pol Pharm. 2012; 69:1372–1379.
- Licznerska B, Baer-Dubowska W. Estrogen intracrinology: Therapy and chemoprevention of brest cancer. Post Hig Med Dosw. 2010;64:220–230.
- Martin BM, Reiter R, Pham T, et al. Estrogen-like activity of metals in Mcf-7 breast cancer cells. Endocrinology. 2003;144:2425–2436.
- Soto AM, Calabro JM, Prechti NV, et al. Androgenic and estrogenic activity in water bodies receiving cattle feedlot effluent in eastern Ne-braska USA. Environ Health Persp. 2004;112:346–352.
- Matejczyk M, Zalewski P. Związki endokrynnie aktywne i ich aktywność biologiczna. Kosmos. 2011;60:17–32.
- Belous AR, Hachey DL, Dawling S, Roodi N, Parl FF. Cytochrome P450 1B1-mediated estrogen metabolism results in estro-gen-deoxyribonucleoside adduct formation. Cancer Res. 2007;67:812–817.
- Długosz A, Sawicka E, Marchewka Z. Styrene and ethylene glycol heave a synergistic effect on lipids peroxidation, that is better protected than repaired by CoQ10. Toxicol In Vitro. 2005;19:581–589.
- Lowry OH, Rosbrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem. 1951;193:265–275.
- Długosz A, Piotrowska D. Lipid peroxidation stimulated by solvesso, bawanol and methanol and its counteraction by antioxidants in human placental mitochondria. Toxicol In Vitro. 2002;16:649–656.
- Buege JA, Aust SD. Microsomal lipid peroxidation. Methods in Enzymology. 1978;52:302–310.
- Stocks J, Offerman EL, Model CB, Dormandy TL. The susceptibility to autooxidation of human red cell lipids in health and disease. Br J Haematol. 1972;23:713–724.
- Rice-Evans CA, Diplock AT, Symons MCR. Techniques in free radical research. Amsterdam, London, New York, Tokyo, Elsevier; 1991.
- Mistra HP, Fridovich I. Superoxide dismutase: Photo-chemical augmention assay. Arch Biochem Biophys. 1985;181:308–312.
- Woolliams JA, Wiener G, Anderson PH, McMurray CH. Variation in the activities of glutathione peroxidase and superoxide dismutase and in the concentration of copper in the blood in various breed crosses of sheep. Res Vet Sci. 1983;34(3):253–256.
- Tamaki H, Yamamoto K, Kumagai H. Expression of two gluthatione S-transferase genes in the yeast issatchenkiaorientalis is induced by o-dinitrobenzene during cell growth arrest. J Bacteriol. 1999;181: 2958–2962.
- Asatiani N, Sapojnikova N, Abuladze M, et al. Effects of CrVI long-term and low-dose action on mammalian antioxidant enzymes (an in vitro study). J Inorg Biochem.2004;98:490–496.
- Stachowiak G, Połać I, Jędrzejczyk S, Pertyński T, Stetkiewicz T. Antyoksydacyjne działanie estrogenów. Prz Menopauz. 2003;2:19–22.
- Rogan E. Xenoestrogens, biotransformation and differential risks for breast cancer. Altern Ther Health Med. 2007;13:112–121.
- Muñoz-Castañeda JR, Muntané J, Muñoz MC, Bujalance I, Montilla P, Túnez I. Estradiol and catecholoestrogens protect against adriamy-cin-induced oxidative stress in erythrocytes of ovariectomized rats. Toxicol Lett. 2005;160:196–203.
- Długosz A, Roszkowska A, Zimmer M. Oestradiol protects against the harmful effects of fluoride more by increasing thiol group levels than scavenging hydroxyl radicals. Basic Clin Pharmacol Toxicol. 2009;105:366–373.
- Sowers MF, Mc Connell D, Jannausch ML, et al. Oestrogen metabolites in relation to isoprostanes as a measure of oxidative stress. Clin Endo-crinol. 2008;68:806–813.
- Tang M, Abplanalp W, Ayres S, Subbiah MT. Superior and distinct antioxidant effects of selected estrogen metabolites on lipid peroxidation. Metab Clin Exp. 1996;45:411–414.
- Seeger H, Mueck AO, Lippert TH. Effect of estradiol metabolites on the susceptibility of low density lipoprotein to oxidation. Life Sci. 1997;61:865–868.
- Świtalska M, Strządała L. Non-genomic action of estrogens. Post Hig Med Dosw. 2007;61:541–547.
- Długosz A, Rembacz KP, Pruss A, Durlak M, Lembas-Bogaczyk J. Influence of chromium on the natural antioxidant barrier. Pol J Environ Stud. 2012;21:331–335.
- Doucet DR, Bonitz RP, Feinman R, Colorado I, Ramanathan M, Feketeova E. Principles and practice of medicine. In: Churchill Livingstone, ed. New York, 2002:889–956.
- Machiedo GW, Zaets S, Berezina T, Xu DZ, Spolarics Z, Deitch EA. Red blood cell damage after trauma-hemorrhage is modulated by gender. J Trauma. 2004;56:837–844.
- Felty Q, Roy D. Estrogen, mitochondria and growth of cancer and non-cancer cells. J Carcinog. 2005;4:1–18.
- Dugan LL, Sensi SL, Canzoniero LM, Handran SD, Rothman SM, Lin TS. Mitochondrial production of reactive oxygen species in cortical neurons following exposure to N-methyl-D-aspatrate. J Neurosci. 1995;15:6377–6388.
- Kabat GC, O’Leary ES, Gammon MD, et al. Estrogen metabolism and breast cancer. Epidemiology. 2006;17:80–88.