Ceylan Aslı F. IŞIK, Erdoğan Özlem B. TULMAÇ, Fügen AKTAN, NURAY ARI, FATMA GÜLGÜN OZANSOY

Östrojen yerine koyma tedavisinin overektomili ve overektomili-diyabetik sıçanlarda doku lipid peroksidasyonu ve antioksidan enzim aktiviteleri üzerine etkisi

Menopoz ve diyabet, birbirinden bağımsız olarak serbest radikal üreten durumlardır. Postmenopozal dönemde kullanılan östrojen yerine koyma tedavisi, antioksidan özelliği nedeniyle pek çok yararlı etkiye sahiptir. Çalışma grupları: overektomi (n=8), overektomi+17β-östradiol (n=8), overektomi+diyabet (n=10) ve overektomi+diyabet+17β- östradiol (n=8) biçimindedir. Overektomiden 1 hafta sonra streptozotosin (45 mg/kg) ile diyabet oluşturulmuş ve sonrasında başlanan tedeavi 17β-östradiol (0.1 mg/kg /gün) ile oral olarak 8 hafta sürdürülmüştür. Süre sonunda hayvanların aort ve uterus dokuları alınmış, malondialdehit konsantrasyonu ile glutatyon peroksidaz ve katalaz aktiviteleri ölçülmüştür. Östrojen tedavisinin kan glukozu üzerine belirgin bir etkisinin olmadığı, tedavinin plazma östradiol konsantrasyonlarını yükselttiği saptanmıştır. Aortda diyabetik ve diyabetik olmayan overektomili gruplarda artmış olan malondialdehit konsantrasyonunun östrojen tedavisiyle düşürüldüğü, uterusta ise tedavinin diyabetik durumda malondialdehit konsantrasyonunu azaltırken, sadece overektomi yapılan hayvanlarda arttırdığı bulunmuştur. Östrojen tedavisinin, aortda artmış olan glutatyon peroksidaz ve katalaz aktivitelerini düşürdüğü, uterusta ise arttırdığı görülmüştür. Sonuçlarımız, tedavinin doku çeşidine göre prooksidan ya da antioksidan gibi davrandığını göstermektedir.

Anahtar Kelimeler:

Östrojen replasman tedavisi, Oksidatif stres, Overektomi, Modeller, hayvan, Sıçan, Wistar, Lipid peroksidasyonu, Kadın, Diabetes mellitus

Effects of estrogen replacement therapy on lipid peroxidation and antioxidant enzyme activities of ovariectomized and ovariectomized-diabetic rats

Menopause and diabetes are conditions producing free radicals independently from each other. Estrogen replacement therapy which widely used in postmenopausal period has beneficial effects because of its antioxidant property. The study groups were as follows: ovariectomy (n=8), ovariectomy+17β-östradiol (n=8), ovariectomy+diabetes (n=10) and ovariectomy+diabetes+17β-östradiol (n=8). Diabetes was induced by streptozotocin (45 mg/kg i.p.) and the treatment with 17β-östradiol (0.1 mg/kg/day) was started a week after ovariectomy. After–week long experimental period aortic and uterine tissues were collected from the animals and the malondialdehyde concentration, glutathione peroxidase and catalase activities were quantified. The treatment did not effect blood glucose concentrations, but increased plasma estradiol concentrations. Increased malondialdehyde concentrations were reduced by the treatment in aorta from diabetics and nondiabetics, but the treatment increased malondialdehyde concentrations in nondiabetic uterine while were reducing in diabetic uterine. The treatment also reduced the increased activities of catalase and glutathione peroxidase in aorta from diabetics and nondiabetics, on the other hand the treatment increased the activities of those enzymes in uterine from diabetics and nondiabetics. Our results suggested that estrogen acts as an antioxidant or prooxidant depending on the tissues.

Keywords:

Estrogen Replacement Therapy, Oxidative Stress, Ovariectomy, Models, Animal, Rats, Wistar, Lipid Peroxidation, Female, Diabetes Mellitus,

PDF

___

1. Khan NS, Malthora S. Effect of hormone replacement therapy on cardiovascular disease: current opinion. Expert Opin Pharmacother, 2003; 4: 667–674.
2. Grimes DA, Lobo RA. Perspectives on the Women's Health Initiative trial of hormone replacement therapy. Obstet Gynecol, 2002; 100: 1344–1353.
3. Gerhard M, Ganz P. How do we explain the clinical benefits of estrogen? From bedside to bench. Circulation, 1995; 92: 5–8.
4. Guiochon-Mantel A. Regulation of the differentiation and proliferation of smooth muscle cells by the sex hormones. Rev Mal Respir, 2000; 17: 604–608.
5. Green PS, Gordon K, Simpkins JW. Phenolic A ring requirement for the neuroprotective effects of steroids. J Steroid Biochem Mol Biol, 1997; 63: 229–235.
6. Ozansoy G, Akın B, Aktan F, Karasu C. Short-term gemfibrozil treatment reverses lipid profile and peroxidation but does not alter blood glucose and tissue antioxidant enzymes in chronically diabetic rats. Mol Cell Biochem, 2000; 216: 59–63.
7. Hunkar T, Aktan F, Ceylan A, Karasu C. Effects of cod liver oil on tissue antioxidant pathways in normal and streptozotocin-diabetic rats. Cell Biochem Funct, 2002; 20: 297–302.
8. Munoz-Castaneda JR, Muntane J, Herencia C, et all. Ovariectomy exacerbates oxidative stress and cardiopathy induced by adriamycin. Gynecol Endocrinol, 2006; 22: 74–79.
9. Oztekin E, Tiftik AM, Baltaci AK, Mogulkoc R. Lipid peroxidation in liver tissue of ovariectomized and pinealectomized rats: effect of estradiol and progesterone supplementation. Cell Biochem Funct, 2006; 7: 551–554.
10. Munoz-Castaneda JR, Montilla P, Munoz MC, et all. Effect of 17-beta-estradiol administration during adriamycin-induced cardiomyopathy in ovariectomized rat. Eur J Pharmacol, 2005; 523: 86–92.
11. Kim YD, Farhat MY, Myers AK, et all. 17-Beta estradiol regulation of myocardial glutathione and its role in protection against myocardial stunning in dogs. J Cardiovasc Pharmacol, 1998; 32: 457–465.
12. Bolego C, Cignarella A, Zancan V, et all (1999). Diabetes abolishes the vascular protective effects of estrogen in female rats. Life Sci, 1999; 64: 741–749.
13. Yagi K. Lipid peroxides and human disase. Chem Phys. Lipids, 1987; 45: 337–351.
14. Lawrence RA, Burk RF. Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun, 1976; 71: 952–958.
15. Aebi HE. Catalase in vitro. Methods Enzymol, 1983; 105: 121–126.
16. Carr MC. The emergence of the metabolic syndrome with menopause. J Clin Endocrinol Metab, 2003; 88: 2404–2411.
17. Chu MC, Cosper P, Orio F, Carmina E, Lobo RA. Insulin resistance in postmenopausal women with metabolic syndrome and the measurements of adiponectin, leptin, resistin, and ghrelin. Am J Obstet Gynecol, 2006;194:100-104.
18. Choi SB, Jang JS, Park S. Estrogen and exercise may enhance beta-cell function and mass via insulin receptor substrate 2 induction in ovariectomized diabetic rats. Endocrinology, 2005; 146: 4786–4794.
19. Kavanagh K, Koudy WJ, Wagner JD. Naturally occurring menopause in cynomolgus monkeys: changes in hormone, lipid, and carbohydrate measures with hormonal status. J Med Primatol, 2005; 34: 171–177.
20. Pfaffman MA, Hilman R, Darby A. Contractile and relaxing activity of arterial smooth muscle from streptozotocin-diabetic rats. Res Commun ChemPathol Pharmacol, 1980; 30: 283–299.
21. Ceylan A, Karasu C, Aktan F, Ozansoy G. Simvastatin treatment restores vasoconstriction and the inhibitory effect of LPC on endothelial relaxation via affecting oxidizing metabolism in diabetic rats. Diabetes Nutr Metab, 2004; 17: 203–210.
22. Geary GG, Krause DN, Duckles SP. Estrogen reduces myogenic tone through a nitric oxide-dependent mechanism in rat cerebral arteries. Am J Physiol, 1998; 275: H292-H300
23. Ha BJ, Lee SH, Kim HJ, Lee JY. The Role of Salicornia herbacea in Ovariectomy- Induced Oxidative Stress. Biol Pharm Bull, 2006; 29: 1305–1309.
24. Gomez-Zubeldia MA, Corrales S, Arbues J, Nogales AG., Millan J.C. Influence of estradiol and gestagens on oxidative stress in the rat uterus. Gynecol Oncol, 2002; 86: 250–258.
25. Gomez-Zubeldia MA, Hinchado G, Arbues JJ, Nogales AG, Millan JC. Influence of estradiol on oxidative stress in the castrated rat uterus. Gynecol Oncol, 2001; 80: 227–232.
26. Kakkar R, Kalra J, Mantha SV, Prasad K. Lipid peroxidation and activity of antioxidant enzymes in diabetic rats. Mol.Cell Biochem, 1995; 151: 113-119.
27. Si ML, Al-Sharafi B, Lai CC, et all. Gender difference in cytoprotection induced by estrogen on female and male bovine aortic endothelial cells. Endocrine, 2001; 15: 255– 262.
28. Zhang L, Fuji S, Kosaka H. Effect of oestrogen on reactive oxygen species production in the aortas of ovariectomized Dahl salt-sensitive rats. J Hypertens, 2007; 25: 407–414.
29. Martucci CP, Fishman J. P450 enzymes of estrogen metabolism. Pharmacol Ther, 1993; 57: 237–257.
30. Wang MY, Dhingra K, Hittelman WN, et all. Lipid peroxidation-induced putative malondialdehyde-DNA adducts in human breast tissues. Cancer Epidemiol Prev, 1996; 5: 705–710.
31. Mobley JA, Bhat AS, Brueggemeier RW. Measurement of oxidative DNA damage by catechol estrogens and analogues in vitro. Chem Res Toxicol,1999; 12: 270–277.