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Horm Metab Res 2001; 33(10): 608-611
DOI: 10.1055/s-2001-17908
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

Coadministration of Melatonin and Estradiol in Rats: Effects on Oxidant Status

F. Gürdöl, S. Genç, Y. Öner-İyidogan, R. Süzme
  • Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Turkey
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Publication History

Publication Date:
18 October 2001 (online)

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This study was designed to investigate the effects of melatonin and estradiol (E2) on lipid peroxidation and antioxidant defense enzymes in blood and liver tissue when administered in vivo. Wistar albino rats were divided into three experimental groups and treated with either estradiol (25 mg/kg bw, s.c.), melatonin (i. p.), or melatonin plus E2, whereas control animals had diluent injections only. Melatonin was given 10 mg/kg bw × 2 intraperitoneally 30 min before and 60 min after E2 treatment to the melatonin plus E2 group. Animals were sacrificed three hours after the estradiol injection, and their blood and liver tissues were prepared for biochemical analyses. Tissue malondialdehyde (MDA) levels and antioxidant enzyme activities - superoxide dismutase (SOD) and glutathione peroxidase (GPx) - were determined in the postmitochondrial fraction, and the results were compared. Estradiol injection caused significant increases in both MDA levels and GPx activity in liver. When melatonin was administered in combination with E2, the effect of estradiol on MDA levels was abolished. A significant decrement in SOD activity occurred in melatonin-treated animals. GPx activity in the blood of E2 plus melatonin-injected animals was significantly higher than those in control animals. Melatonin-treated animals exhibited relatively lower levels of SOD activity than those from the control and E2 plus melatonin groups. This indicates that estradiol could exert oxidant action resulting in an increment in tissue malondialdehyde levels. Enhanced activity of GPx in both liver and blood following melatonin injection may indicate the contribution of this neurohormone on the antioxidant defense.

Key words:

Estradiol - Malondialdehyde - Melatonin - Antioxidant - Lipid Peroxidation

References

  • 1 Liehr J G, Roy D. Free radical generation by redox cycling of estrogens.  Free Radic Biol Med. 1990;  8 415-423
    CrossrefPubMedGoogle Scholar
  • 2 Wang M Y, Liehr J. Induction by estrogens of lipid peroxidation and lipid peroxide-derived malonaldehyde-DNA adducts in male Syrian hamsters: role of lipid peroxidation in estrogen-induced kidney carcinogenesis.  Carcinogenesis. 1995;  16 1941-1945
    PubMedGoogle Scholar
  • 3 Walker B E. Uterine tumors in old female mice exposed prenatally to diethylstilbestrol.  J Natl Cancer Inst. 1983;  70 477-484
    PubMedGoogle Scholar
  • 4 Mooradian A D. Antioxidant properties of steroids.  J Steroid Biochem Molec Biol. 1993;  45 509-511
    PubMedGoogle Scholar
  • 5 Leal A M, Ruiz-Larrea M B, Martinez R, Lacort M. Cytoprotective actions of estrogens against tert-butyl hydroperoxide-induced toxicity in hepatocytes.  Biochem Pharmacol. 1998;  56 1463-1469
    CrossrefPubMedGoogle Scholar
  • 6 Ruiz-Larrea M B, Martin C, Babenko N A, Martinez R, Lacort M. Diethylstilbestrol antagonizes the oxidant-induced transformations of membrane phospholipids.  Biochem Soc Trans. 1998;  26 224
    PubMedGoogle Scholar
  • 7 Arteaga E, Rojas A, Villaseca P, Bianchi M. The effect of 17β-estradiol and alpha-tocopherol on the oxidation of LDL cholesterol from postmenopausal woman and the minor effect of gamma-tocopherol and melatonin.  Menopause. 2000;  7 112-116
    PubMedGoogle Scholar
  • 8 Sugioka K, Shimosegawa Y, Nakano M. Estrogens as natural antioxidants of membrane phospholipid peroxidation.  FEBS Lett. 1987;  210 37-39
    CrossrefPubMedGoogle Scholar
  • 9 Tiidus P M. Can estrogens diminish exercise-induced muscle damage?.  Can J Appl Physiol. 1995;  20 26-38
    PubMedGoogle Scholar
  • 10 Gürdöl F, Öner-İyidoğan Y, Yalçın Ö, Genç S, Buyru F. Changes in enzymatic antioxidant defense system in blood and endometrial tissues of women after menopause.  Res Commun Molec Pathol Pharmacol. 1997;  97 38-45
    PubMedGoogle Scholar
  • 11 Gürdöl F, Genç S, Yalçın Ö, Düzköylü O. Association of hormone replacement therapy with plasma total antioxidant capacity in postmenopausal women.  Turk J Gynecol Obstet. 1997;  11 216-220
    PubMedGoogle Scholar
  • 12 Köse K, Doğan P, Özesmi C. Contraceptive steroids increase erythrocyte lipid peroxidation in female rats.  Contraception. 1993;  47 421-425
    CrossrefPubMedGoogle Scholar
  • 13 Genç S, Gürdöl F, Öner-İyidogan Y, Süzme R. Acute effects of estradiol and of diethylstilbestrol: pro- or antioxidant potential?.  Res Commun Molec Pathol Pharmacol. 1999;  105 253-261
    PubMedGoogle Scholar
  • 14 Reiter R J, Carneiro R C, Oh C S. Melatonin in relation to cellular antioxidative defense mechanisms.  Horm Metab Res. 1997;  29 363-372
    PubMedGoogle Scholar
  • 15 Conti M, Morand P C, Levillain P, Lemonnier A. Improved fluorometric determination of malondialdehyde.  Clin Chem. 1991;  37 1273-1275
    PubMedGoogle Scholar
  • 16 Sun Y, Oberley L W, Li Y. A simple method for clinical assay of superoxide dismutase.  Clin Chem. 1988;  34 497-500
    CrossrefPubMedGoogle Scholar
  • 17 Paglia O E, Valentine W N. Studies on the quantitative characterization of erythrocyte glutathione peroxidase.  J Lab Clin Med. 1967;  70 158-169
    PubMedGoogle Scholar
  • 18 Lowry O H, Rosebrough N J, Farr A L, Randall R J. Protein measurement with the Folin phenol reagent.  J Biol Chem. 1951;  193 265-275
    PubMedGoogle Scholar
  • 19 Van Kampen E J, Zijlstra W G. Determination of hemoglobin and its derivates.  Adv Clin Chem. 1965;  8 141-187
    PubMedGoogle Scholar
  • 20 Mor M, Plazzi P V, Spaloni G, Tarzia G. Melatonin.  Current Med Chem. 1999;  6 501-518
    PubMedGoogle Scholar
  • 21 Menendez-Pelaez A, Reiter R J. The distribution of melatonin in mammalian tissues: The relative importance of nuclear verses cytosolic localization.  J Pineal Res. 1993;  15 59-69
    Google Scholar
  • 22 Milczarek R, Klimek J, Zelewski L. Melatonin inhibits NADPH-dependent lipid peroxidation in human placental mitochondria.  Horm Metab Res. 2000;  32 84-85
    PubMedGoogle Scholar
  • 23 Mates J M, Perez-Gomez C, De Castro I N. Antioxidant enzymes and human diseases.  Clin Biochem. 1999;  32 595-603
    CrossrefPubMedGoogle Scholar
  • 24 Shull S, Heintz N H, Periasamy M, Manohar M, Janssen Y M, Marsh J P, Mossman B T. Differential regulation of antioxidant enzymes in response to oxidants.  J Biol Chem. 1991;  266 24 398-24 403
    PubMedGoogle Scholar
  • 25 Kelner M J, Bagnell R. Alteration of endogenous glutathione peroxidase, manganese superoxide dismutase, and glutathione transferase activity in cells transfected with a copper-zinc superoxide dismutase expression vector. Explanation for variations in paraquat resistence.  J Biol Chem. 1990;  265 10 872-10 875
    PubMedGoogle Scholar
  • 26 Ji L L, Dillon D, Wu E. Myocardial aging: antioxidant enzyme systems and related biochemical properties.  Am J Physiol. 1991;  261 R386-R392
    PubMedGoogle Scholar
  • 27 Gupta A, Hasan M, Chander R, Kapoor N K. Age-related elevation in lipid peroxidation products: dimunition of superoxide dismutase activity in the central nervous system of rats.  Gerontology. 1991;  37 305-309
    PubMedGoogle Scholar
  • 28 Ceballos-Picot I, Nicole A, Clement M, Bourre J M, Sinet P M. Age-related changes in antioxidant enzymes and lipid peroxidation in brains of control and transgenic mice overexpressing copper-zinc superoxide dismutase.  Mutation Res. 1992;  275 281-293
    PubMedGoogle Scholar
  • 29 Ledig M, Tholey G, Megias-Megias L, Kopp P, Wedler R. Combined effects of ethanol and manganese on cultured neurons and glia.  Neurochem Res. 1991;  16 591-596
    CrossrefPubMedGoogle Scholar
  • 30 Uysal M, Kutalp G, Seçkin Ş. The effect of cholesterol feeding on lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in the liver of rats.  Inter J Vit Nutr Res. 1988;  58 339-342
    PubMedGoogle Scholar
  • 31 Somani S M, Husain K, Diaz-Phillips L, Lanzotti D J, Kareti K R, Trammell G L. Interaction of exercise and ethanol on antioxidant enzymes in brain regions of the rat.  Alcohol. 1996;  13 603-610
    CrossrefPubMedGoogle Scholar
  • 32 Guemouri L, Artur Y, Herbeth B, Jeandel C, Cuny G, Siest G. Biological variability of superoxide dismutase, glutathione peroxidase and catalase in blood.  Clin Chem. 1991;  37 1932-1937
    PubMedGoogle Scholar
  • 33 Prohaske J, Sunde R. Comparison of liver glutathione peroxidase activity and mRNA in female and male mice and rats.  Comp Biochem Physiol. 1993;  105B 111-116
    PubMedGoogle Scholar
  • 34 Massafra C, De Felice C, Gioia D, Buonocore G. Variations in erythrocyte antioxidant glutathione peroxidase activity during the menstrual cycle.  Clin Endocrinol. 1998;  49 63-67
    CrossrefPubMedGoogle Scholar
  • 35 Reiter R J, Tan D X, Kim S J, Qi W. Melatonin as a pharmacological agent against oxidative damage to lipids and DNA.  Proc West Pharmacol Soc. 1998;  41 229-236
    PubMedGoogle Scholar
  • 36 Antolin I, Rodriguez C, Sainz R M, Mayo J C, Aria H, Kotler M, Rodriguez-Colunga M J, Tolivia D, Menendez-Pelaez A. Neurohormone melatonin prevents cell damage: effect on gene expression of antioxidative enzymes.  FASEB J. 1996;  10 882-890
    PubMedGoogle Scholar
  • 37 Kotler M, Rodriguez C, Sainz R M, Antolin I, Menendez-Pelaez A. Melatonin increases gene expression for antioxidant enzymes in rat brain cortex.  J Pineal Res. 1998;  24 83-89
    PubMedGoogle Scholar
  • 38 Pablos M I, Agapito M T, Gutierrez R, Recio J M, Reiter R J, Barlow-Walden C R, Acuna-Castroviejo D, Menendez-Pelaez A. Melatonin stimulates the activity of the detoxifying enzyme glutathione peroxidase in several tissues of chicks.  J Pineal Res. 1995;  19 111-115
    PubMedGoogle Scholar
  • 39 Genç S, Gürdöl F, Öner-İyidogan Y, Onaran I. The effect of melatonin administration on ethanol-induced lipid peroxidation in rats.  Pharmacol Res. 1998;  37 37-40
    CrossrefPubMedGoogle Scholar
  • 40 Knapen M FCM, Zusterzeel P LM, Peters W HM, Steegers E AP. Glutathione and glutathione-related enzymes in reproduction. A review.  Eur J Obstet Gynecol Reprod Biol. 1999;  82 171-184
    CrossrefPubMedGoogle Scholar

Prof. Figen Gürdöl

Department of Biochemistry
Istanbul Faculty of Medicine

Çapa, Istanbul 34390
Turkey


Phone: + 90 (212) 5312670

Fax: + 90 (212) 6311323, ext. 115

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