Füsun AK SONAT, Deniz BAĞDAŞ, Zülfiye GÜL, Gözde R. ÖZALP

Tavşanlarda Orta Dönem Gebeliklerin Sonlandırılmasında Kullanılan Aglepriston'un Bazı Oksidatif Stres Parametreleri Üzerine Etkisi

Aglepriston son yıllarda küçük hayvan hekimliğinde abort indüksiyonları için başarıyla kullanılabilen bir progesteron reseptör antagonistidir. Yapılan klinik çalışmalarda ilacın hiçbir yan etkisinin olmadığı belirtilmişse de oksidatif stres üzerine etkisi hakkında bilgi bulunmamaktadır. Bu çalışmada tavşanlarda orta dönem gebeliklerin sonlandırılması için uygulanan aglepristonun, oksidatif stres parametreleri olan Malondialdehit (MDA), Süperoksit Dismutaz (SOD) ve redükte Glutatyon (GSH) üzerine etkisinin araştırılması amaçlandı. Çalışmada kullanılan 12 aylık yaşta 15 adet Yeni Zelanda Beyaz tavşanı kontrollü olarak çiftleştirildi ve çiftleştirildikleri gün gebeliklerinin 0. günü olarak kabul edildi. Gebe olan tavşanlar rastgele üç gruba ayrıldı. Grup I (kontrol) tavşanlarına gebeliğin 15. ve 16. gününde 1ml/3kg olacak şekilde % 0.9 NaCl, Grup II tavşanlarına gebeliğin 15. gününde, Grup III tavşanlarına ise gebeliğin 15. ve 16. gününde 10 mg/kg dozda subkutan (s.c.) olarak aglepristone (Alizin®) enjeksiyonu yapıldı. Tavşanlardan alınan kan örneklerinde MDA, SOD ve GSH ölçümleri yapıldı. Grup III de MDA seviyesinde artış saptandı. Bu artış Grup I (p

Anahtar Kelimeler:

Aglepriston, Süperoksid dismutaz, Malondialdehit, Glutatyon, Tavşan.

Tavşanlarda Orta Dönem Gebeliklerin Sonlandırılmasında Kullanılan Aglepriston'un Bazı Oksidatif Stres Parametreleri Üzerine Etkisi

Aglepristone is a safe and effective abortifacient, which is being widely used in small animal practice during the last years. Although no side effetcs have been reported in clinical studies, there is no information available about the effects of aglepristone on oxidative stress parameters. The objective of this study was to investigate the effects of aglepristone treatment on oxidative stress parameters, which are Malondialdehyt (MDA), Superoxide Dismutase (SOD) ve reduced Glutathione (GSH), in mid-gestation termination in rabbits. Fifteen healthy New Zealand White rabbit, 12 months of age, were included the the study. They were given to fertile bucks and the mating day was recorded as the 0 day of pregnancy. The does were randomly divided into Yrd.Doç.Dr., Uludağ Üniversitesi Veteriner Fakültesi Fizyoloji Anabilim Dalı Görükle Kampüsü/BURSA Araş.Gör.Dr., Uludağ Üniversitesi Tıp Fakültesi Deney Hayvanları Yetiştirme Uygulama Merkezi Görükle Kampüsü /BURSA Araş.Gör., Uludağ Üniversitesi Tıp Fakültesi Farmakoloji Anabilim Dalı Görükle Kampüsü/BURSA4* Doç.Dr.,Uludağ Üniversitesi Veteriner Fakültesi Doğum ve Jinekoloji Anabilim Dalı Görükle Kampüsü/BURSA, rgozalp@uludag.edu.trthree groups. In Group I (control) the does were injected with 0.9% NaCl at dose of 1ml/3kg on day 15 and 16 post-mating. In Group II and Group III, aglepristone (Alizin®) was applied at a dose of 10mg/kg dose ofsubcutaneously, on day 15 and on days 15-16 days post-mating, respectively. MDA, SOD and GSH levels were measured from collected blood samples. A marked increase of MDA in Group III, was statistically significant with Group I (p

Keywords:

Aglepristone, Superokside dismutase, Malondialdehyt, Glutathione, Rabbit.,

PDF

___

Ascensao AA, Magalhaes JF, Soares JM, Ferreira RM, Neuparth MJ, Appell HJ, Duarte JA, 2005. Cardiac mitochondrial respiratory function and oxidative stress: the role of exercise. Int. J. Sports Med., 26, 258.
Chang CC, Wang WC, Bardin CW., 1993. Termination of earlypregnancy in therat, rabbit, andhamsterwith RU 486 andanordrin. Contraception, 47:597–608.
Chang CC, Wang CC, Bardin CW, 1993a. Postcoitaluse of anordrinand RU 486 forprevention of implantation in therat. Contraception, 47, 413– 4
Chang CC, Wang CC, Bardin CW, 1993b. Termination of early pregnancy in the rat, rabbit, and hamster with RU 486 and anordrin. Contraception, 47, 597–608.
Chang CC, Wang CC, Bardin CW, 1993c. Anordiol is more potent than an ordrin for terminatin gpregnancy when administered with RU 486. Contraception, 47, 609–616.
Çaylak E.,2011. Hayvan ve bitkilerde oksidatif stress ile antioksidanlar. Tıp Araştırmaları Dergisi, 9(1), 73-83.
Damasceno DC, Volpato GT, Calderon IMP, Rudge MVC, 2002. Oxidative stres and diabetes in pregnant rats. Animal Rep. Sci., 72, 235-244.
Dao B, Vanage G, Marshall A, Bardin CW, Koide SS, 1996. Anti-implantation activity of antiestrogens and mifepristone. Contraception, 54, 253–258.
Demir M, Vural CD, Yılmaz N, Yüksel Ş, Vural H, Sezer MT, 2007. Tek seans hemodiyalizin çeşitli oksidatif stress markerları üzerine etkisi. Tıp Araştırmaları Dergisi, 5(2), 74-77.
Derviş E., 2011. Oral antioksidanlar. Dermatoz, 2(1), 263-267.
Dursun E, Özben T, Süleymanlar G, Dursun B, Yakupoğlu G, 2002. Effect of hemodialysis on the oxidative stress and antioxidants. Clin. Chem. Lab. Med., 40,1009-1013.
Ellman GL., 1959. Tissue sulfhydryl groups. Arch. Biochem. Biophys., 82:70–7.
Fieni F, Tainturier D, Bruyas JF, Bdinand F, Berthelot X, Ronsin P, Rachail M, Lefay MP., 19 Etudecliniqued’une antihormonepourprovoquerl’avortementchez la chienne. Recueil de Me´decineVe´te´rinaire, 172:359–67. Fieni F, Martal J, Marnet PG, Siliart B, Bernarnd F, Riou M, Bruyas JF, Tainturier D., 2001. Hormonalvariation in bitchesafterearlyormidpregnancyterminationwithaglepristone (RU534). J ReprodFertilSuppl, 57:243–8.
Fieni F, Martal J, Marnet PG, Siliart B, Guittot F., 2006. Clinical, biologicalandhormonalstudy of mid-pregnancytermination in catswithaglepristone. Theriogenology, 66:1721–8.
Galac S, Kooistra HS, Butinar J, Bevers MM, Dieleman SJ, Voorhout G, Okkens AC., 2000. Termination of mid-gestation pregnancy in bitches with aglepristone, a progesterone receptor antagonist. Theriogenology, 53:941–50.
Georgiev P, Wehrend A., 2006. Mid-gestation pregnancy termination by the progesterone receptor blocker aglepristone in queens. Theriogenology, 65:1401–6.
Georgiev P, Wehrend A, Penchev G, Vodenicharov A, Kauffold J, Leiser R. Histologicalchanges of thefelinecervix, endometrium and placenta after mid-gestational termination of pregnancy with aglepristone. Reprod. Domes Anim; baskıda. Gündoğan F, Elwood G, Mark P, Feijoo A, Longato L, Tong M, Monte SM, 2010. EthanolInduced Oxidative Stress and Mitochondrial Dysfunction in Rat Placenta: Relevance to Pregnancy Loss. Alcohol Clin. Exp. Res., 34(3), 415-423.
Halliwell B, Gutteridge JMC, 1999. Free radicals, other reactive species and disease in Free Radicals in Biology and Medicine, edited by Halliwell, B & Gutteridge, J.M.C, (Oxford University Press: New York, USA), sf.639.
Hoffmann B, Schuler G., 2000. Receptor blockers—general aspects with respect to their use in domestic animal reproduction. Anim Reprod Sci., 60/61:295–312.
Hubler M, Arnold S., 2000. Prevention of pregnancy in bitches with the progesterone antagonist aglepristone (alizine). SchweizerArchivfu¨rTierheilkunde, 142:381–6.
Klemm A, Voigt C, Friedrich M, 2001. Determination of erythrocyte antioxidant capacity in haemodialysis patients using electron paramagnetic resonance. Nephrol. Dial. Transplant., 16, 216621
Koca N, Karadeniz F., 2002. Serbest radikal oluşum mekanizmaları ve vücuttaki antioksidan savunma sistemleri. Gıda Mühendisliği Dergisi.
Liu AX, He WH, Yin LJ, Lv PP, Zhang Y, Sheng JZ, Leung PCK, Huang HF, 2011. Sustained Endoplasmic Reticulum Stress as a Cofactor of Oxidative Stress in Decidual Cells from Patients with Early Pregnancy Loss. J. Clin. Endocrinol Metab., 96(3), E493-E497.
Morena M, Cristol JP, Bosc JY, 2002. Convective and diffusive losses of vitamine C during haemodiafiltration session: a contributive factor to oxidative stres in haemodialysis patient. Nephrol. Dial. Transplant., 17,422-427.
Ohkawa H, Ohishi N, Yagi K., 1979. Assayforlipidperoxides in animal tissues by thiobarbituricacid reaction. Anal Biochem, 95:351–8.
Özalp GR, Seyrek–Intas¸ K, Calıskan C¸ , Wehrend A, 2008. Mid-gestation pregnancy termination in rabbits by the progesterone antagonist aglepristone. Theriogenology, 69, 1056–1060.
Özalp GR., Çalışkan Ç., Seyrek-İntaş K., Wehrend A., 2010. Effects of the progesterone receptor antagonist aglepristone in implantation administered on days 6 and 7 after mating in rabbits. Reprod. Dom. Anim., 45, 505–508; doi: 1111/j.1439-0531.2008.01282.x
Özalp GR, Temizel EM, Ozocak-Batmaz E., 20 Clinical, ultrasonography and haematology of aglepristone-induced mid-gestation pregnancy terminations in rabbits. J S Afr Vet Assoc. May, 6;84(1):E1-5. doi: 10.4102/jsava.v84i1.998.
Özden M, Maral H, Akaydın D, Çetinalp P, Kalender B, 2002. Erythrocyte glutathione peroxidase activity, plasma malondialdehyde and erythrocyte glutathione levels in hemodialysis and CAPD patients. Clin. Biochem., 35,269-273. Philibert D., 1994. RU 46534 Affinite´ relative de liaisonpourlesre´cepteursste´roidiens- activite´ antiprogeste´rone in vivo. Rapportd’e´tude interne Roussel Uclaf.
Saksena SK, Chang MC, Lau IF., 1979. Termination of pregnancy in rabbit and mouse by Trichosanthin. Contraception, 20:367–76.
Salomy M, Golstein PJ, 1978. Prevention of pregnancy in rabbit sus ingvaginal application of prostaglandin F2a. Fertil Steril, 29, 456–458.
Sies H.,1993. Strategies of antioxidant defense. Eur. J. Biochem., 215, 213-219.
Steiger K, Politt E, Hoeftmann T, MeyerLindenberg A, Schoon HA, Guenzel-Apel AR., 200 Morphology of canine placental sites after induced embryonic or fetal death. Theriogenology, 66:1709–14.
Sun Y, Oberley LW, Li Y., 1988. A simple method for clinical assay of superoxide dismutase. Clin. Chem., 34:497–500.
Troudi A, Bouaziz H, Soudani N, Amara IB, Boudawara T, Touzani H, Lyoussi B, Zeghal N, 20 Neurotoxicity and oxidative stress induced by gibberellic acid in rats during late pregnancy and early postnatal periods: Biochemical and histological changes. Experimental and Toxicologic Pathology, 64, 583-590. Uzun D, Korkmaz GG, Sitar ME, Cebe T, Yanar K, Çakatay U, Aydın S., 2013. Oxidative damage parameters in renal tissues of aged and young rats based on gender. Clinical Interventions in Aging, 8, 809-815.