Araştırma Makalesi
BibTex RIS Kaynak Göster

Amitriptilinin Çipura (Sparus aurata) Serum Biyokimyası Üzerindeki Etkisi

Yıl 2022, Cilt: 2 Sayı: 1, 66 - 75, 29.04.2022

Osman Nezih Kenanoğlu Nihan Akıncı Kenanoğlu Sevdan Yılmaz Soner Bilen

Öz

Amitriptilin, depresyonun yanında, birçok nöropatik ve infalamatuar hastalığın tedavisinde sıklıkla kullanılan trisiklik antidepresandır. Bu çalışmada, sucul ortama karışması sonucunda uzun süre kalıcılık gösterme özelliğine sahip olan amitriptilin antidepresanının çipura (Sparus aurata) balıklarının serum biyokimyasına olan etkisi araştırılmıştır. Bu amaçla çipura balıkları 14 gün boyunca 0,2 µg/L, 10 µg/L, 100 µg/L ve 1 mg/L’lik amitriptilin konsantrasyonlarına maruz bırakılmıştır. Çalışmanın 7. ve 14. gününde alınan balıkların kan serum örneklerinden glukoz (GLU), albumin (ALB), globulin (GLO), total protein (TPROT), trigliserit (TRİ), kolesterol (KOL), aspartat aminotransferaz (AST), alanin aminotransferaz (ALT), alkalen fosfataz (ALP) ve laktat dehidrogenaz (LDH) biyokimyasal parametreleri belirlenmiştir. 7. günde anlamlı bir farklılık göstermeyen tüm serum biyokimya parametrelerinden, trigliserid, kolesterol, AST, ALP ve LDH değerlerinde 14. günde anlamlı değişimler meydana gelmiştir (p<0,05). Bu sonuçlar farklı amitriptilin konsantrasyonlarının balık biyokimyasında önemli değişimlere neden olduğunu ortaya koymaktadır.

Anahtar Kelimeler

Sparus aurata amitriptilin serum biyokimyası

Kaynakça

  • [1]. C. Barbui, M. Hotopf, “Amitriptyline v. the rest: still the leading antidepressant after 40 years of randomised controlled trials” Br J Psychiatry, vol. 178, pp. 129-144, Feb 2001, doi: 10.1192/bjp.178.2.129. PMID: 11157426.
  • [2]. M. Yang, W. Qiu, J. Chen, J. Zhan, C. Pan, X. Lei, M. Wu, “Growth inhibition and coordinated physiological regulation of zebrafish (Danio rerio) embryos upon sublethal exposure to antidepressant amitriptyline”. Aquat Toxicol., vol. 151, pp 68-76, Jun 2014
  • [3]. K.A. Demin, T.O Kolesnikova., S.L. Khatsko, D.A. Meshalkina, E.V. Efimova, Y.Y. Morzherin, A.V. Kalueff, “Acute effects of amitriptyline on adult zebrafish: Potential relevance to antidepressant drug screening and modeling human toxidromes” Neurotoxicol Teratol., vol. 62, pp. 27-33, Jul 2017, doi: 10.1016/j.ntt.2017.04.002. Epub 2017 Apr 22. PMID: 28438663.
  • [4]. V. Calisto, V.I. Esteves, “Psychiatric pharmaceuticals in the environmen”t. Chemosphere, vol: 77 (10), pp. 1257–1274, 2009.
  • [5]. M.R. Bautista-Ferrufino, M.D. Cordero, J.A. Sánchez-Alcázar, M. Illanes, A. Fernández-Rodríguez, P. Navas, M. de Miguel, “Amitriptyline induces coenzyme Qdeficiency and oxidative damage in mouse lung and liver” Toxicol. Lett., vol. 204 (1), pp. 32–37, 2011.
  • [6]. I. M. Sebastine, R. J. Wakeman. "Consumption and environmental hazards of pharmaceutical substances in the UK." Process Safety and Environmental Protection vol. 81.4, pp. 229-235, 2003.
  • [7]. A. Lajeunesse, C. Gagnon, S. Sauvé, “Determination of Basic Antidepressants and Their N-Desmethyl Metabolites in Raw Sewage and Wastewater Using Solid-Phase Extraction and Liquid Chromatography−Tandem Mass Spectrometry”. Anal. Chem., vol. 80 (14), pp. 5325–5333, 2008, doı: 10.1021/ac800162q
  • [8]. D. R. Baker, B. Kasprzyk-Hordern, “Multi-residue analysis of drugs of abuse in wastewater and surface water by solid-phase extraction and liquid chromatography– positive electrospray ionisation tandem mass spectrometry”. J. Chromatogr., vol. 1218 (12), pp. 1620–1631, 2011, doı: 10.1016/j.chroma.2011.01.060
  • [9]. H. Ziarrusta, L. Mijangos, A. Prieto, N. Etxebarria, O. Zuloaga, M. Olivares, “Determination of tricyclic antidepressants in biota tissue and environmental waters by liquid chromatography-tandem mass spectrometry”. Anal. Bioanal. Chem., vol., 408 (4), pp. 1205–1216, 2016. doı: 10.1007/s00216-015-9224-y.
  • [10]. H. Ziarrusta, L. Mijangos, U. Izagirre, M.M. Plassmann, J.P. Benskin, E. Anakabe, M. Olivares, O. Zuloaga, “Bioconcentration and biotransformation of amitriptyline in gilthead bream”. Environmental science & technology, vol. 51(4), pp. 2464-2471, 2017.
  • [11]. P. P. Fong, A. T. Ford, “The biological effects of antidepressants on the molluscs and crustaceans: A review”. Aquat. Toxicol., vol. 151, pp. 4−13, 2014.
  • [12]. L. Minguez, E. Farcy, C. Ballandonne, A. Lepailleur, A. Serpentini, J-M. Lebel, R. Bureau, M-P. Halm-Lemeille, “Acute toxicity of 8 antidepressants: What are their modes of action?” Chemosphere, vol. 108, pp. 314−319, 2014.
  • [13]. S.L. Klosterhaus, R. Grace, M.C. Hamilton, and D. Yee, “Method validation and reconnaissance of pharmaceuticals, personal care products, and alkylphenols in surface waters, sediments, and mussels in an urban estuary” Environment international, vol. 54, pp.92-99, 2013.
  • [14]. H. Ziarrusta, A. Ribbenstedt, L. Mijangos, S. Picart-Armada, A. Perera-Lluna, A. Prieto, U. Izagirre, JP Benskin, M. Olivares, O. Zuloaga, N. Etxebarria, “Amitriptyline at an Environmentally Relevant Concentration Alters the Profile of Metabolites Beyond Monoamines in Gilthead Bream”. Environ Toxicol Chem., vol. 38(5): pp. 965-977, May 2019. doi: 10.1002/etc.4381. Epub 2019 Apr 2. PMID: 30702171.
  • [15]. M. Iversen, B. Finstad, R. S. McKinley, R.A. Eliassen, “The efficacy of metomidate, clove oil, Aqui-S™ and Benzoak® as anaesthetics in Atlantic salmon (Salmo salar L.) smolts, and their potential stress-reducing capacity”. Aquaculture, vol. 221: pp. 549-566, 2003.
  • [16]. S. Yılmaz, S. Ergün, “Effects of garlic and ginger oils on hematological and biochemical variables of sea bass Dicentrarchus labrax”. Journal of Aquatic Animal Health, vol. 24: pp. 219-224, 2012.
  • [17]. C.E. Bond,. “Circulation, respiration, and the gas bladder”. In C. E. Bond (ed.) Biology of Fishes. W. B Saunders Company Press, London, UK, 1979, pp. 347-374.
  • [18]. G. Rey Vázquez, G.A. Guerrero, “Characterization of blood cells and hematological parameters in Cichlasoma dimerus (Teleostei, Perciformes)”. Tissue and Cell, vol. 39, pp. 151-160, 2007.
  • [19]. M. Kanyılmaz, N. Tekellioğlu, “Effects of dietary zeolite levels on some blood parameters of gilthead seabream (Sparus aurata) juveniles”. Journal of Aquaculture Engineering and Fisheries Research, vol. 2(3), pp. 119-127, 2016.
  • [20]. D.G. McDonald, C.L. Milligan, “Chemical Properties of the Blood”. Academic Press, Inc., California. pp. 56-113, 1992.
  • [21]. O. Demir, “Tilapia Oreochromis Mossambicus (Peters, 1852) Balıklarının Yemlerinde Balık Yağı Yerine Yerfıstığı Yağı Kullanılmasının Büyüme Performansı, Yem Değerlendirme, Vücut Kompozisyonu Ve Serum Biyokimyasına Etkisi”, Muğla Sıtkı Koçman Üniversitesi Fen Bilimleri Enstitüsü Su Ürünleri Mühendisliği Anabilim Dalı, 2019, Muğla.
  • [22]. J.D. Morgan, G.K. Iwama, ” Measurements of Stressed States in the Field”. Cambridge University Press, Cambridge. pp. 247-270, 1997.
  • [23]. T.W. Moon, “Glucose Intolerance in Teleost Fish: Fact or Fiction?”. Comp Biochem Phys B, vol. 129: pp. 243-249, 2001
  • [24]. G.G. Gunter, L. L Sulya, B. E. Box, “Some Evolutionary Patterns in Fishes' Blood”. Biological Bulletin. pp. 121. 1961, 10.2307/1539434.
  • [25]. G.H. Satchell, “Physiology and Form of Fish Circulation” Cambridge University Press, Cambridge. 1991, pp. 235.
  • [26]. G.F.Wiegertjes, R.J.M. Stet, H.K. Parmentier, W.B. Van Muiswinkel, “Immunogenetics of disease resistance in Changes in biochemical, histological and specific immune parameters 151 fish; a comparable approach”. Dev. Comp. Immunol. 20, pp. 365–381, 1996.
  • [27]. S. Mayer, “A review of the scientific justifications for Maintaining cetaceans in captivity, (edit. By Frances Clarke), A report for the whale and dolphin conservation society (WDCS)”, 35 p., 1998.
  • [28]. E. Ş. Çelik, S. Bilgin, “Bazi balik türleri için kan protein ve lipidlerinin standardizasyonu”. Erciyes Üniversitesi Fen Bilimleri Enstitüsü Fen Bilimleri Dergisi, vol. 23(1), pp. 215-229, 2007.
  • [29]. B. Magnadottir, “Innate Immunity of Fish (overview)”. Fish Shellfish Immun, vol. 20(2): pp. 137–151, 2006.
  • [30]. M.F. Laker, “Klinik Biyokimya” (Ulukaya, E., Tokullugil A., Gür, E., Dirican, M., Tuncel, P., Ulukaya, E., vd. çev.), s. 343, Uludağ Üniv. Tıp Fak. Biyokimya ABD., Nobel Tıp Kitapevleri Ltd.Şti., İstanbul, 1996.
  • [31]. H. Karagül, A. Altıntaş, U.R. Fidancı, T. Sel, “Klinik Biyokimya”, s. 430, Cilt 1, Medisan Yayın Evi, Yayın No: 45, Ankara, 2000.
  • [32]. L. Stryer, “Biochernistry”, Freeman and Company, San Francisco, pp 470-476. 1975.
  • [33]. M. Atamanalp, M. Yilmaz, H.İ. Haliloğlu, “Comparing Serum Cholesterol Types and Levels of Three Trout Species (Salvelinus alpinus, Salmo trutta fario and Oncorhynchus mykiss)”, Journal of Applied Animal Research, vol. 23:2, pp. 223-226, 2003. doi: 10.1080/09712119.2003.9706425
  • [34]. Ö. Fırat, H.Y. Cogun, T.A. Yüzereroğlu, G. Gök, Ö. Fırat, F. Kargin, Y. Kötemen, “A comparative study on the effects of a pesticide (cypermethrin) and two metals (copper, lead) to serum biochemistry of Nile tilapia, Oreochromis niloticus”. Fish Physiology and Biochemistry, vol. 37(3), pp. 657-666, 2011.
  • [35]. J. Vaclavik, P. Sehonova, N. Hodkovicova, L. Vecerkova, J. Blahova, A. Frangi, P. Marsalek, J. Mares, F. Tichy, Z. Svobodova, C. Faggio, “The effect of foodborne sertraline on rainbow trout (Oncorhynchus mykiss)”. Science of the Total Environment, vol. 708, 135082, 2020.

Effect of Amitriptyline on Serum Biochemistry of Gilthead Sea Bream (Sparus aurata)

Yıl 2022, Cilt: 2 Sayı: 1, 66 - 75, 29.04.2022

Osman Nezih Kenanoğlu Nihan Akıncı Kenanoğlu Sevdan Yılmaz Soner Bilen

Öz

Amitriptyline is a tricyclic antidepressant that is frequently used in the treatment of many neuropathic and inflammatory diseases as well as depression. In this study, the effect of amitriptyline antidepressant, which has long-lasting properties as a result of contamination to the aquatic environment, on the serum biochemistry of sea bream (Sparus aurata) fish was investigated. For this purpose, sea bream were exposed to amitriptyline concentrations of 0.2 µg/L, 10 µg/L, 100 µg/L and 1 mg/L for 14 days. Glucose (GLU), albumin (ALB), globulin (GLO), total protein (TPROT), triglyceride (TRI), cholesterol (COL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) biochemical parameters were determined from the blood serum samples of the fish taken on the 7th and 14th days of the study. While all serum biochemistry parameters did not show a significant difference on the 7th day, significant changes occurred in the triglyceride, cholesterol, AST, ALP and LDH values on the 14th day (p<0.05). These results reveal that different amitriptyline concentrations cause significant changes in fish biochemistry.

Anahtar Kelimeler

Sparus aurata amitriptyline serum biochemistry

Kaynakça

  • [1]. C. Barbui, M. Hotopf, “Amitriptyline v. the rest: still the leading antidepressant after 40 years of randomised controlled trials” Br J Psychiatry, vol. 178, pp. 129-144, Feb 2001, doi: 10.1192/bjp.178.2.129. PMID: 11157426.
  • [2]. M. Yang, W. Qiu, J. Chen, J. Zhan, C. Pan, X. Lei, M. Wu, “Growth inhibition and coordinated physiological regulation of zebrafish (Danio rerio) embryos upon sublethal exposure to antidepressant amitriptyline”. Aquat Toxicol., vol. 151, pp 68-76, Jun 2014
  • [3]. K.A. Demin, T.O Kolesnikova., S.L. Khatsko, D.A. Meshalkina, E.V. Efimova, Y.Y. Morzherin, A.V. Kalueff, “Acute effects of amitriptyline on adult zebrafish: Potential relevance to antidepressant drug screening and modeling human toxidromes” Neurotoxicol Teratol., vol. 62, pp. 27-33, Jul 2017, doi: 10.1016/j.ntt.2017.04.002. Epub 2017 Apr 22. PMID: 28438663.
  • [4]. V. Calisto, V.I. Esteves, “Psychiatric pharmaceuticals in the environmen”t. Chemosphere, vol: 77 (10), pp. 1257–1274, 2009.
  • [5]. M.R. Bautista-Ferrufino, M.D. Cordero, J.A. Sánchez-Alcázar, M. Illanes, A. Fernández-Rodríguez, P. Navas, M. de Miguel, “Amitriptyline induces coenzyme Qdeficiency and oxidative damage in mouse lung and liver” Toxicol. Lett., vol. 204 (1), pp. 32–37, 2011.
  • [6]. I. M. Sebastine, R. J. Wakeman. "Consumption and environmental hazards of pharmaceutical substances in the UK." Process Safety and Environmental Protection vol. 81.4, pp. 229-235, 2003.
  • [7]. A. Lajeunesse, C. Gagnon, S. Sauvé, “Determination of Basic Antidepressants and Their N-Desmethyl Metabolites in Raw Sewage and Wastewater Using Solid-Phase Extraction and Liquid Chromatography−Tandem Mass Spectrometry”. Anal. Chem., vol. 80 (14), pp. 5325–5333, 2008, doı: 10.1021/ac800162q
  • [8]. D. R. Baker, B. Kasprzyk-Hordern, “Multi-residue analysis of drugs of abuse in wastewater and surface water by solid-phase extraction and liquid chromatography– positive electrospray ionisation tandem mass spectrometry”. J. Chromatogr., vol. 1218 (12), pp. 1620–1631, 2011, doı: 10.1016/j.chroma.2011.01.060
  • [9]. H. Ziarrusta, L. Mijangos, A. Prieto, N. Etxebarria, O. Zuloaga, M. Olivares, “Determination of tricyclic antidepressants in biota tissue and environmental waters by liquid chromatography-tandem mass spectrometry”. Anal. Bioanal. Chem., vol., 408 (4), pp. 1205–1216, 2016. doı: 10.1007/s00216-015-9224-y.
  • [10]. H. Ziarrusta, L. Mijangos, U. Izagirre, M.M. Plassmann, J.P. Benskin, E. Anakabe, M. Olivares, O. Zuloaga, “Bioconcentration and biotransformation of amitriptyline in gilthead bream”. Environmental science & technology, vol. 51(4), pp. 2464-2471, 2017.
  • [11]. P. P. Fong, A. T. Ford, “The biological effects of antidepressants on the molluscs and crustaceans: A review”. Aquat. Toxicol., vol. 151, pp. 4−13, 2014.
  • [12]. L. Minguez, E. Farcy, C. Ballandonne, A. Lepailleur, A. Serpentini, J-M. Lebel, R. Bureau, M-P. Halm-Lemeille, “Acute toxicity of 8 antidepressants: What are their modes of action?” Chemosphere, vol. 108, pp. 314−319, 2014.
  • [13]. S.L. Klosterhaus, R. Grace, M.C. Hamilton, and D. Yee, “Method validation and reconnaissance of pharmaceuticals, personal care products, and alkylphenols in surface waters, sediments, and mussels in an urban estuary” Environment international, vol. 54, pp.92-99, 2013.
  • [14]. H. Ziarrusta, A. Ribbenstedt, L. Mijangos, S. Picart-Armada, A. Perera-Lluna, A. Prieto, U. Izagirre, JP Benskin, M. Olivares, O. Zuloaga, N. Etxebarria, “Amitriptyline at an Environmentally Relevant Concentration Alters the Profile of Metabolites Beyond Monoamines in Gilthead Bream”. Environ Toxicol Chem., vol. 38(5): pp. 965-977, May 2019. doi: 10.1002/etc.4381. Epub 2019 Apr 2. PMID: 30702171.
  • [15]. M. Iversen, B. Finstad, R. S. McKinley, R.A. Eliassen, “The efficacy of metomidate, clove oil, Aqui-S™ and Benzoak® as anaesthetics in Atlantic salmon (Salmo salar L.) smolts, and their potential stress-reducing capacity”. Aquaculture, vol. 221: pp. 549-566, 2003.
  • [16]. S. Yılmaz, S. Ergün, “Effects of garlic and ginger oils on hematological and biochemical variables of sea bass Dicentrarchus labrax”. Journal of Aquatic Animal Health, vol. 24: pp. 219-224, 2012.
  • [17]. C.E. Bond,. “Circulation, respiration, and the gas bladder”. In C. E. Bond (ed.) Biology of Fishes. W. B Saunders Company Press, London, UK, 1979, pp. 347-374.
  • [18]. G. Rey Vázquez, G.A. Guerrero, “Characterization of blood cells and hematological parameters in Cichlasoma dimerus (Teleostei, Perciformes)”. Tissue and Cell, vol. 39, pp. 151-160, 2007.
  • [19]. M. Kanyılmaz, N. Tekellioğlu, “Effects of dietary zeolite levels on some blood parameters of gilthead seabream (Sparus aurata) juveniles”. Journal of Aquaculture Engineering and Fisheries Research, vol. 2(3), pp. 119-127, 2016.
  • [20]. D.G. McDonald, C.L. Milligan, “Chemical Properties of the Blood”. Academic Press, Inc., California. pp. 56-113, 1992.
  • [21]. O. Demir, “Tilapia Oreochromis Mossambicus (Peters, 1852) Balıklarının Yemlerinde Balık Yağı Yerine Yerfıstığı Yağı Kullanılmasının Büyüme Performansı, Yem Değerlendirme, Vücut Kompozisyonu Ve Serum Biyokimyasına Etkisi”, Muğla Sıtkı Koçman Üniversitesi Fen Bilimleri Enstitüsü Su Ürünleri Mühendisliği Anabilim Dalı, 2019, Muğla.
  • [22]. J.D. Morgan, G.K. Iwama, ” Measurements of Stressed States in the Field”. Cambridge University Press, Cambridge. pp. 247-270, 1997.
  • [23]. T.W. Moon, “Glucose Intolerance in Teleost Fish: Fact or Fiction?”. Comp Biochem Phys B, vol. 129: pp. 243-249, 2001
  • [24]. G.G. Gunter, L. L Sulya, B. E. Box, “Some Evolutionary Patterns in Fishes' Blood”. Biological Bulletin. pp. 121. 1961, 10.2307/1539434.
  • [25]. G.H. Satchell, “Physiology and Form of Fish Circulation” Cambridge University Press, Cambridge. 1991, pp. 235.
  • [26]. G.F.Wiegertjes, R.J.M. Stet, H.K. Parmentier, W.B. Van Muiswinkel, “Immunogenetics of disease resistance in Changes in biochemical, histological and specific immune parameters 151 fish; a comparable approach”. Dev. Comp. Immunol. 20, pp. 365–381, 1996.
  • [27]. S. Mayer, “A review of the scientific justifications for Maintaining cetaceans in captivity, (edit. By Frances Clarke), A report for the whale and dolphin conservation society (WDCS)”, 35 p., 1998.
  • [28]. E. Ş. Çelik, S. Bilgin, “Bazi balik türleri için kan protein ve lipidlerinin standardizasyonu”. Erciyes Üniversitesi Fen Bilimleri Enstitüsü Fen Bilimleri Dergisi, vol. 23(1), pp. 215-229, 2007.
  • [29]. B. Magnadottir, “Innate Immunity of Fish (overview)”. Fish Shellfish Immun, vol. 20(2): pp. 137–151, 2006.
  • [30]. M.F. Laker, “Klinik Biyokimya” (Ulukaya, E., Tokullugil A., Gür, E., Dirican, M., Tuncel, P., Ulukaya, E., vd. çev.), s. 343, Uludağ Üniv. Tıp Fak. Biyokimya ABD., Nobel Tıp Kitapevleri Ltd.Şti., İstanbul, 1996.
  • [31]. H. Karagül, A. Altıntaş, U.R. Fidancı, T. Sel, “Klinik Biyokimya”, s. 430, Cilt 1, Medisan Yayın Evi, Yayın No: 45, Ankara, 2000.
  • [32]. L. Stryer, “Biochernistry”, Freeman and Company, San Francisco, pp 470-476. 1975.
  • [33]. M. Atamanalp, M. Yilmaz, H.İ. Haliloğlu, “Comparing Serum Cholesterol Types and Levels of Three Trout Species (Salvelinus alpinus, Salmo trutta fario and Oncorhynchus mykiss)”, Journal of Applied Animal Research, vol. 23:2, pp. 223-226, 2003. doi: 10.1080/09712119.2003.9706425
  • [34]. Ö. Fırat, H.Y. Cogun, T.A. Yüzereroğlu, G. Gök, Ö. Fırat, F. Kargin, Y. Kötemen, “A comparative study on the effects of a pesticide (cypermethrin) and two metals (copper, lead) to serum biochemistry of Nile tilapia, Oreochromis niloticus”. Fish Physiology and Biochemistry, vol. 37(3), pp. 657-666, 2011.
  • [35]. J. Vaclavik, P. Sehonova, N. Hodkovicova, L. Vecerkova, J. Blahova, A. Frangi, P. Marsalek, J. Mares, F. Tichy, Z. Svobodova, C. Faggio, “The effect of foodborne sertraline on rainbow trout (Oncorhynchus mykiss)”. Science of the Total Environment, vol. 708, 135082, 2020.
Toplam 35 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Ekoloji
Bölüm Araştırma Makaleleri
Yazarlar

Osman Nezih Kenanoğlu 0000-0002-5097-6656

Nihan Akıncı Kenanoğlu 0000-0002-3917-6412

Sevdan Yılmaz 0000-0002-4809-5809

Soner Bilen 0000-0001-9459-8178

Yayımlanma Tarihi 29 Nisan 2022
Yayımlandığı Sayı Yıl 2022 Cilt: 2 Sayı: 1

Kaynak Göster

IEEE O. N. Kenanoğlu, N. Akıncı Kenanoğlu, S. Yılmaz, ve S. Bilen, “Amitriptilinin Çipura (Sparus aurata) Serum Biyokimyası Üzerindeki Etkisi”, Etoxec, c. 2, sy. 1, ss. 66–75, 2022.
 Kapak Resmi İndir