2,3,7,8-Tetraklorodibenzo-p-Dioksin ile Oksidatif Strese Maruz Kalan Sıçanlarda Kuersetinin Koruyucu Etkisinin Araştırılması

Bu çalışmada, 28 adet Wistar Albino erkek sıçan rastgele dört eşit gruba ayrıldı. 2,3,7,8-tetraklorodibenzo-p-dioksin (TCDD) 2 µg/kg/hafta dozda intraperitonal olarak uygulandı, kuersetin 20 mg/kg/gün dozda gavajla uygulandı, ve kuersetin+TCDD birlikte sırasıyla 20 mg/kg/gün ve 2 µg/kg/hafta dozlarda uygulandı. Tüm uygulamalar sekiz hafta boyunca gerçekleştirildi. Sekizinci haftanın sonunda sıçanlar sakrifiye edildi ve kalp ve damar dokuları spektrofotometrik yöntemle biyokimyasal analizler (redükte glutatyon (GSH), glutatyon peroksidaz (GSH-Px), katalaz (CAT), süperoksit dismutaz (SOD) ve tiyobarbitürik asit reaktif sübstansları (TBARS) düzeyleri) için alındı. Çalışmanın sonucunda, TCDD sıçanlarda antioksidan aktiviteleri önemli ölçüde azaltmış ve lipid peroksidasyonunu arttırmıştır. Aksine, kuersetinin artan SOD, CAT, GSG ve GSH-Px düzeyleri ile TCDD’nin toksik etkisini önemli ölçüde engellediği ancak TBARS oluşumunu azalttığı belirlenmiştir. Bu nedenle, kuersetinin TCDD ve diğer çevresel kirleticiler tarafından oluşan toksisiteye karşı tedavi potansiyeline sahip olduğu ve özellikle insanlarda kardiyovasküler rahatsızlıklara bağlı ölüm riskini azaltabileceği önerilebilir.

The Investigation of Protective Effect of Quercetin in Rats Exposed to Oxidative Stress by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin

In this study, 28 Wistar Albino male rats were randomly divided into four equal groups. 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) was intraperitoneally administered at the dose of 2 µg/kg/week, quercetin was administered at the doseof 20 mg/kg/day by gavages, and quercetin+TCDD were intraperitoneally administered at the doses of 20 mg/kg/day and2 µg/kg/week, respectively. All applications were performed for 8 weeks. At the end of the eighth week, the rats weresacrificed and their heart and vascular tissues were taken for biochemical analysis (reduced glutathione (GSH), glutathioneperoxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD) and thiobarbituric acid reactive substance (TBARS) levels)by spectrophotometric method. As a result of the study, TCDD significantly decreased antioxidant activities and increasedlipid peroxidation in rats. In contrast, quercetin significantly prevented the toxic effects of TCDD via increasing SOD, CAT,GSH and GSH-Px levels but decreased the formation of TBARS. Therefore, it can be suggested that quercetin has thepotential for treatment against the toxicity caused by TCDD or other environmental contaminants and can decrease the riskof mortality due to cardiovascular diseases, especially in humans

PDF

___

1. O. Ciftci, Dioksinli Bileşiklerin Etki Mekanizması, Kimyasal Yapısı ve Toksikokinetik Özelliklerinin İncelenmesi, İnönü Üniv. Tıp Fak. Derg., 17 (2010) 413-422.
2. R. Pohjanvirta and J. Tuomisto, Short-term toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in laboratory animals: effects, mechanisms and animal models, Pharmacol. Rev., 46 (1994) 483-549.
3. E.A. Hassoun, J. Vodhanel, B. Holden, A. Abushaban, The effects of ellagic acid and vitamin E succinate on antioxidant enzymes activities and glutathione levels in different brain regions of rats after subchronic exposure to TCDD, J. Toxicol. Environ. Health. A., 69 (2006) 381-393.
4. P. Goldmann, Most severe acute chloracne, a mass intoxication caused by 2,3,6,7-tetrachlordibenzodioxine, Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete, 24 (1973) 149-152.
5. J. England, Herbicides and coronary ectasia, Med. J. Aust., 2 (1981) 260.
6. J. Pazderova-Vejlupkova, M. Nemcova, J. Píckova, L. Jirásek, E. Lukas, The development and prognosis of chronic intoxication by tetrachlordibenzo-p-dioxin in men, Arch. Environ. Healt., 36 (1981) 5-11.
7. O. Ciftci, S. Tanyildizi, A. Godekmerdan, Protective effect of curcumin on immune system and body weight gain on rats intoxicated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), Immunophar. Immunotoxic., 32 (2010) 99-104.
8. Z.S. Talas, I. Ozdemir, O. Ciftci, O. Cakir, M.F. Gulhan and O.M. Pasaoglu, Role of propolis on biochemical parameters in kidney and heart tissues against L-NAME induced oxidative injury in rats, Clin. Exp. Hypertens., 36 (2014) 492-496.
9. H. Kurita, V.S. Carreira, Y. Fan, M. Jiang, M. Naticchioni, S. Koch, J. Rubinstein, A. Puga, Ah receptor expression in cardiomyocytes protects adult female mice from heart dysfunction induced by TCDD exposure, Toxicol., 355–356 (2016) 9–20.
10. A. Abushouk, A.M.A. Salem, M.M. Abdel-Daim, Berberis vulgaris for cardiovascular disorders: a scoping literature review, Iran. J. Basic. Med. Sci., 20 (2017) 503-510.
11. M.S. Mohsenzadeh, B.R. Zanjani, G. Karimi, Mechanisms of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cardiovascular toxicity: An overview, Chem.-Biolog. Interac., 282 (2018) 1–6.
12. M. Sagit, F. Korkmaz, S.G. Gurgen, R. Gundogdu, A. Akcadag, I. Ozcan, Quercetin attenuates the gentamicin-induced ototoxicity in a rat model, Internati. J. Pediat. Otorhinolaryng, 79 (2015) 2109–2114.
13. S. Atashpour, S. Fouladdel, T.K. Movahhed, E. Barzegar, M.H. Ghahremani, S.N. Ostad, et. al., Quercetin induces cell cycle arrest and apoptosis in CD133+ cancer stem cells of human colorectal HT29 cancer cell line and enhances anticancer effects of doxorubicin, Iran. J. Basic. Med. Sci., 18 (2015) 635–643.
14. Y. Li, Y. Zhao, W. Yu, S. Jiang, Scavenging ability on ROT of alpha-lipoic acid, Food Chem., 84 (2004) 563-567.
15. H. Sies, Biochemistry of oxidative stress, Angew. Chem. Int. Ed., 25 (1986) 1058-1071.
16. M. Richter, R. Ebermann, B. Marian, Quercetin-induced apoptosis in colorectal tumor cells: possible role of EGF receptor signaling, Nutr. Cancer., 34 (1999) 88–99.
17. I. Murtaza, G. Marra, R. Schlapbach, A. Patrignani, M. Künzli, U. Wangner, J. Sabates, A. Dutt, A preliminary investigation demonstrating the effect of quercetin on the expression of genes related to cellcycle arrest, apoptosis and xenobiotic metabolism in human CO115 colon-adenocarcinoma cells using DNA microarray, Biotechnol. Appl. Biochem., 45 (2006) 29-36.
18. F. Perez-Vizcaino and J. Duarte, Flavonols and cardiovascular disease, Mol. Aspects. Med., 31 (2010) 478-494.
19. A. Cogolludo, G. Frazziano, A.M. Briones, L. Cobeno, L. Moreno, F. Lodi, M. Salaices, J. Tamargo, F. Perez-Vizcanio, The dietary flavonoid quercetin activates BKCa currents in coronary arteries via production of H2 O2 , Role in vasodilatation, Cardiovasc. Res., 73 (2007) 424-431.
20. C. Menendez, R. Jimenez, L. Moreno, P. Galindo, A. Cogolludo, J. Duarte, F. Perez-Vizcanio, Lack of synergistic interaction between quercetin and catechin in systemic and pulmonary vascular smooth muscle, Br. J. Nutr., 105 (2011) 1287-1293.
21. J. Duarte, R. Perez-Palencia, F. Vargas, M.A. Ocete, F. PerezVizcaino, A. Zarzuelo, J. Tamargo, Antihypertensive effects of the flavonoid quercetin in spontaneously hypertensive rats, Br. J. Pharmacol., 133 (2001) 117-124.
22. K. Yagi, Assay of lipid peroxidation in blood plasma or serum, Methods. Enzymol., 105 (1984) 328-331.
23. J. Sedlak and R.H. Lindsay, Estimation of total, proteinbound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent, Anal. Biochem., 25 (1968) 192-205.
24. Y. Sun, L.W. Oberley, Y. Li, A simple method for clinical assay of superoxide dismutase, Clin. Chem., 34 (1988) 497-500.
25. H. Aebi, Catalase in vitro assay methods, Method. Enzymol., 105 (1984) 121-126.
26. D.E. Paglia and W.N. Valentine, Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase, J. Lab. Clin. Med., 70 (1967) 158-159.
27. O.H. Lowry, N.J. Rosebrough, A.L. Farr, R.J. Randall, Protein measurement with pholin phenol reagent, J. Biol. Chem., 193 (1951) 265-275.
28. United States Environmental Protection Agency (USEPA), Exposure and Human Health Reassessment of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Compounds, National Academy Sciences (NAS) Review Draft, Part I: Estimating Exposure to Dioxin-Like Compounds, Volume 1: Sources of Dioxin-Like Compounds in the United States, Washington DC. National Center for Environmental Assessment. U.S. Environ. Protect. Agen., 2004.
29. G. Pushpavalli, P. Kalaiarasi, C. Veeramani, K.V. Pugalendi, Effect of chrysin on hepatoprotective and antioxidant status in D-galactosamine-induced hepatitis in rats, Eur. J. Pharmacol., 631 (2010) 36-41.
30. J. Vena, P. Boffetta, H. Becher, T. Benn, H.B. Bueno-deMesquita, D. Coggon, D. Colin, D. Flesch-Janys, L. Green, T. Kauppinen, M. Littorin, E. Lynge, J.D. Mathews, M. Neuberger, N. Pearce, A.C. Pesatori, R. Saracci, K. Steenland, and M. Kogevinas, Exposure to dioxin and nonneoplastic mortality in the expanded IARC international cohort study of phenoxy herbicide and chlorophenol production workers and sprayers, Environ. Health. Perspect., 106 (1998) 645- 653.
31. G.M. Calvert, D.K. Wall, M.H. Sweeney, M.A. Fingerhut, Evaluation of cardiovascular outcomes among U.S. workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin, Environ. Health. Perspect., 106 (1998) 635-643.
32. O. Ciftci, I. Ozdemir, S. Tanyıldizi, S. Sildiz, H. Oguzturk, Antioxidative effects of curcumin, β-myrcene and 1,8-cineole against 2,3,7,8-tetrachlorodibenzo-p-dioxininduced oxidative stress in rats liver, Toxicol. Ind. Health., 27 (2011) 447-453.
33. S. Fatih, Farklı dozlarda 2,3,7,8-Tetraklorodibenzo-p-dioksin tarafından ratlarda beyin, karaciğer, böbrek ve kalp gibi dokularda oluşturulan oksidatif stres üzerine likopenin koruyuculuğu, Doktora Tezi, Farmakoloji ve Toksikoloji ABD, Elazığ, 2008.
34. O. Ciftci, N. Vardı, I. Ozdemir, Effects of quercetin and chrysin on 2,3,7,8-tetrachlorodibenzo-p-dioxin induced hepatotoxicity in rats, Environ. Toxicol., 28 (2013) 146-154.
35. Y. Yuksel, R. Yuksel, M. Yagmurca, H. Haltas, H. Erdamar, M. Toktas and O. Ozcan, Effects of quercetin on methotrexateinduced nephrotoxicity in rats, Human and Experimen. Toxicol., (2016) 1-11.
36. M.G. Hertog, E.J. Feskens, P.C. Hollman, M.B. Katan, D. Kromhout, Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study, Lancet, 342 (1993) 1007-1011.
37. Ö. Coşkun, M. Kanter, F. Armutçu, K. Çetin, B. Kaybolmaz, Ö. Yazgan, Protective effects of quercetin, a flavonoid antioxidant, in absolute ethanol-induced acute gastric ulcer, Eur. J. Gen. Med., 1 (2004) 37-42.