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THE EFFECTS OF GRAPE SEED AND COLCHICINE ON PENTADECAFLUOROOCTANOIC ACIDE INDUCED HEPATIC DAMAGE ON RATS

Year 2014, Volume: 40 Issue: 2, 191 - 201, 22.07.2014

Abstract

This study aims to determine the effects of grape seed and colchicine on pentadecafluorooctanoicacid (PFOA; Perfluorooctanoic acid) induced hepatic damage and on some serum biochemical parameters. A total of 60 Wistar albino rats (200-250 g) were divided into 6 equal groups. Those in group 1 (controls) received 0.9% saline weekly; group 2 PFOA twice a week; group 3 and 4 PFOA twice in the first week, followed by grape seed extract and colchicine for 4 weeks, respectively; group 5 and 6 received colchicine and grape seed extract for 4 weeks, respectively. Hyperemia, focal bleeding, fat degeneration and increase in connective tissue elements, pronounced in portal sites in particular, and infiltration of lymphoid series cell observed in the livers of the rats in group 2. Histological findings in the rats in group 3 and 4 were similar to those in group 2. Biochemically, there were no statistical differences between the control and experimental groups for serum total protein, albumin and globulin levels (P>0.05). Although total protein, albumin and globulin levels did not changed statistically (P>0.05) in group 3 and 4 compared to group 2, these parameters increased significantly for the rats allocated in the group 5 and 6 (P<0.01, P<0.05). Serum triglyceride and total cholesterol levels, and AST, ALT and ALP activities did not changed significantly (P>0.05). We conclude that grape seed extract and colchicine do not contribute to acute hepatic damage caused by PFOA shot.

Key Words: Colchicine, Pentadecafluorooctanoic acid, rat, grape seed

References

  • Aydın, O., Yıldız, L., Kefeli, M., Barış, S., Kandemir, B., 2005. Kronik viral hepatitlerde ıshak modifiye histolojik aktivite indeksinin tek gözlemci ve gözlemciler arası tekrarlanabilirliği. Türk Patoloji Dergisi 21 (3-4), 58-61.
  • Bagchi, D., Bagchi, M., Stohs, J., Das, D., Ray, S., Kuszynski, C.A., Joshi, S.S., Pruess, H.G., 2000. Free radicals and grape seed proanthocyanidin extract: Importance in human health and disease prevention. Toxicology 148, 187-1
  • Bodenheimer, H., Schaffner, F., Pezzulo, J., 1998. Evalution of colchicine therapy in primary biliary cirrhosis. Journal of Gastroenterology 95, 124-129.
  • Bolarin, D.M., Barker, K., Fuller, G., 1987. Enzyme markers of collagen synthesis in carbon tetrachloride-induced fibrosis and during colchicine modification of CCI 4 induced liver injury. Experımental and Molecular Pathology 46, 145-152.
  • Bouhamidi, V., Prevost, V., Nouvelot, A., 1998. High protection by grape seed proanthocyanidins (GSPC) of polyunsaturated fatty acids against UV-C induced peroxidation. Life Sciences 321, 31Calafat, A.M., Wong, L.Y., Kuklenyik, Z., Reidy, J.A., Needham, L.L., 2007. Polyfluoroalkyl chemicals in the U.S. population: data from the National Health and Nutrition Examination Survey NHANES 2003-2004 and comparisons with NHANES 1999–2000. Environmental Health Perspectives 115 (11), 1596-1602.
  • Chahardehi, A.M., Ibrahim, D., Sulaiman, S.F., 200 Antioxidant activity and total phenolic content of some medicinal plants in Urticaceae family. Journal of Applied Biological Sciences 3, 25-29. Chen, L.C., Tatum, V., Glauert, H.P., Chow, C.K., 200 Peroxisome proliferator perfluorodecanoic acid alters glutathione and related enzymes. Journal of Biochemical and Molecular Toxicology 15, 107-112. Comporti, M., 1985. Biology of disease lipit peroxidation and cellular damage in toxic liver injury. Laboratory Investigation 53, 599-623.
  • Cui, L., Zhou, Q.F., Liao, C.Y., 2009. Studies on the toxicological effects of PFOA and PFOS on rats using histological observation and chemical analysis. Archives of Environmental Contamination and Toxicology 56 (2), 338-349. Cutrin, C., Menino, M.J., Carballo, C., Pazoj, A., Barrio, E., Parafita, M.A., 19 Lactacidaemia in rats with cirrhosis induced by carbon tetrachloride and ethanol: treaetment with colchicine, nifedipine and S-adenosyl methionine. Journal of Research in Medical Sciences 19, 351-352.
  • DePierre, J.W., 2002. Effects on rodents of perfluorofatty acids. In: Neilson, A.H. (Ed), The Handbook of Environmental Chemistry. Berlin, Springer-Verlag, pp. 203-248.
  • DuPont Haskell Laboratory, 1982. Excretion and disposition of 14C-ammonium perfluorooctanoate in male and female rats, mice, hamsters, and rabbits. US EPA Public Docket AR-226. US Environmental Protection Agency, Washington, DC.
  • Freeman, B., Crapo, J.D., 1982. Biology of disease, free radicals and tissue injury. Laboratory Investigation 47, 412-426.
  • Güllüoğlu, M.G., Özlük, Y., Öztürk, A.S., Demir, D., Çevikbaş, U., 2005. Viral hepatitlerin histolojik skorlamasında gözlemciler arası uyum. Türk Patoloji Dergisi 21 (1-2), 3-7.
  • Han, X., Kemper, R.A., Jepson, G.W., 2005. Subcellular distribution and protein binding of perfluorooctanoic acid in rat liver and kidney. Drug and Chemical Toxicology 28 (2), 19720
  • Hosokawa, M., Satoh, T., 1993. Differences in the induction of carboxylesterase isozymes in rat iver microsomes by perfluorinated fatty acids. Xenobiotica 23, 1125-1133.
  • İncioğlu, A., 2008. Kronik hepatit B’nin doğal seyri; ilerleyişi ve prognostik faktörler. Uzmanlık Tezi, T.C. Sağlık Bakanlığı Şişli Etfal Eğitim ve Araştırma Hastanesi Çocuk Sağlığı ve Hastalıkları Kliniği, İstanbul.
  • Kershenobich, D., Vargas, F., Garcia, G., Tamayo, R.P., Gent, M., Rojkind, M., 1988. Colchicine in the treatment of cirrhosis of the liver. New England Journal of Medicine 318, 1709-1713.
  • Kershenobisc, D., Rojkind, M., Quiroga, A.Q., Alcocer-Varela, J., 1990. Effect of colchicines on lymphocyte and monocyte function and its relation to fibroblast proliferation in primary biliary cirrhosis. Journal of Hepatology 9, 20520
  • Kudo, N., Sakai, A., Atsushi, M., Yasuhide, H., Tadashi, T., Yoichi, K., 2007. Tissue distribution and hepatic subcellular distribution of perfluorooctanoic acid at low dose are different from those at high dose in rats. Biological & Pharmaceutical Bulletin 30 (8), 1535-1540.
  • Larson, R.A., 1988. The antioxidants of higher plants. Phytochemistry 27, 969-978.
  • Lau, C., Anitole, K., Hodes, C., Lai, D., PfahlesHutchens A., Seed J., 2007. Perfluoroalkyl acids: a review of monitoring and toxicological findings. Toxicological Sciences 99 (2), 3663
  • Leighton, J.A., Bay, M.K., Maldonado, A.L., Johnson, R.F., Schenker, S., Speeg, K.V., 1990: The effect of liver dysfunction on colchicines pharmacokinetics in the rat. Journal of Hepatology 11, 210-215.
  • Leighton, J.A., Bay, M.K., Maldonado, A.L., Johnson, R.F., Schenker, S., Speeg, K.V., 19 Colchicine clearance is impaired in alcoholic cirrhosis. Journal of Hepatology 14, 1013-1015.
  • Menino, M.J., Cutrin, C., Parafita, M.A., 1993. Effect of colchicines on lactate production by isolated hepatocytes in rats treated with carbon tetrachloride and ethanol. Drug and Alcohol Dependence 32, 181-185.
  • Munoz, R.H., Munoz, M.D., Suarez, J., Sánchez, C.V., 1990. Adenosine partially prevents cirrhosis induced by carbon tetrachloride in rats. Journal of Hepatology 12, 242-248.
  • O’Brien, M.,L., Cunningham, M.,L., Spear, B.,T., Glauert, H.,P., 2001. Effects of peroxisome proliferators on glutathione and glutathione related enzymes in rats and hamsters. Toxicology and Applied Pharmacology 171, 27
  • O’Conner, J.J., 1988. Is colchicines effective therapy for cirrhosis. New England Journal of Medicine 318, 1751-1752.
  • Parola, M., Leonarduzzi, G., Biasi, F., Albano, E., Biocca, M.E., Poli, G., Dianzani, M.U., 1992. Vitamin E dietary supplemantion protects againist carbon tetrachloride induced chronic liver damage and cirrhosis. Journal of Hepatology 16, 1014-1021.
  • Pastoor, T.P., Lee, K.P., Perri, M.A., Gillies, P.J., 19 Biochemical and morphological studies of ammonium perfluorooctanoate-induced hepatomegaly and peroxisome proliferation. Experimental and Molecular Pathology 47, 98 Rojkind, M., Kershenobich, D., 1975. Effect of colchicines on collagen, albumin and transferring synthesis by cirrhotic rat liver slices. Acta Biochimica et Biophysica Sinica 378, 415-423.
  • Sabouraud, A., Rochdi, M., Urtizberea, M., Christen, M.O., Achtert, G., Scherrmann, J.M., 1992. Pharmacokinetics of colchicine: a review of experimental and clinical data. Gastroenterology 30 (1), 35-39.
  • Sato, M., Bagchi, D., Tosaki, A., Das, D., 2001. Grape seed proanthocyanidin reduces cardiomyocyte apoptosis by inhibiting ischemia/reperfusion-induced activation of JNK-1 anad C-JUN. Free Radical Biology and Medicine 31 (6), 729-737.
  • Seitz, H.K., Busenkell, R., Simanowski, U.A., Boesche, J., Kommerell, B., Rojkind, M., 19 Effect of colchicine on in vivo and in vitro ethanol metabolism in the rat. Gastroenterology 25, 270-273. Takagi, A., Sai, K., Umemura, T., Hasegawa, R., Kurokawa, Y., 1992. Hepatomegaly is an early biomarker for hepatocarcinogenesis induced by peroxisome proliferators. Journal of Environmental Pathology, Toxicology and Oncology 11 (3), 145-149.
  • Tebib, K., Rouanet, J., Besancon, P., 1997. Antioxidant effects of dietary polymeric grape seed tannins in tissues of rats fed a high cholesterol-vitamin E deficient diet. Food Chemistry 59 (1), 135-141.
  • Tribble, D.L., Jones, D.P., 1987. The pathological significance of lipit peroxidation in oxidative cell injury. Journal of Hepatology 7, 377-387.
  • U.S. Environmental Protection Agency, 2013. Perfluorooctanoic Acid (PFOA) and Fluorinated Telomers. http://www.epa.gov/oppt/pfoa/, (Erişim Tarihi: 17.01.2013).
  • Wang, D.,H., Ishii, K., Zhen, L.,X., Taketa, K,. 1996. Enhanced liver injury in acatalasemic mice following exposure to carbon tetrachloride. Archives of Toxicology 70, 189-194.
  • White, S.S., Fenton, S.E., Hines, E.P., 2011. Endocrine disrupting properties of perfluorooctanoic acid. Journal of Steroid
  • Biochemistry and Molecular Biology 127 (1-2), 16Ylinen, M., Kojo, A., Hanhijarvi, H., Peura, P., 19 Disposition of perfluooctanoic acid in the rat after single and subchronic administration. Bulletin of Environmental Contamination and Toxicology 44, 46-53.

Ratlarda Pentadekafluorooktanoik Asit ile Oluşturulan Karaciğer Hasarı Üzerine Üzüm Çekirdeği ve Kolşisinin Etkisi

Year 2014, Volume: 40 Issue: 2, 191 - 201, 22.07.2014

Abstract

Çalışmamızda, ratlarda pentadekafluorooktanoik asit (PFOA; perfluorooctanoic acid)  ile oluşturulan karaciğer hasarına üzüm çekirdeği ve kolşisinin etkisi ile bazı serum biyokimyasal parametrelerindeki değişiklikleri belirlemek amaçlandı. Altmış adet Wistar albino rat (200-250 g) 10’arlı altı gruba ayrıldı. Grup 1 (kontrol)’dekilere bir hafta
% 0,9’luk tuzlu su, grup 2’dekilere haftada iki kez pentadekafluorooktanoik asit, grup 3 ve 4’dekilere ilk hafta iki kez pentadekafluorooktanoik asit enjeksiyonunu takiben sırasıyla dört hafta boyunca üzüm çekirdeği ekstresi ve kolşisin, grup 5 ve 6’dakilere dört hafta boyunca sırasıyla kolşisin ve üzüm çekirdeği ekstresi verildi. Histopatolojik olarak; Grup 2’deki ratların karaciğerlerinde hiperemi, fokal kanamalar, yağ dejenerasyonu ile portal bölgelerde daha belirgin bağ doku elemanlarında artış ve lenfoid seri hücre infiltrasyonları gözlendi. Grup 3 ve 4’deki bulgular Grup 2’deki ile benzerdi. Biyokimyasal olarak; serum total protein, albümin ve globülin düzeyleri yönünden kontrol (grup 1) ile deneme grupları (grup 2, 3, 4, 5, 6) arasında istatistiki bir fark saptanmadı (P>0,05). Grup 2’deki ratlara göre Grup 3 ve 4’deki ratlarda total protein, albümin ve globülin düzeylerinde istatistiki olarak bir değişme belirlenmemesine (P>0,05) karşın, Grup 5 ve 6’daki ratlarda bu parametrelerde önemli düzeyde artış (P<0,01; P<0,05) gözlendi. Serum trigliserit ve total kolesterol düzeyleri ile AST, ALT ve ALP aktiviteleri uygulamalardan istatistiki önemde etkilenmedi (P>0,05). Sonuç olarak; pentadekafluorooktanoik asit enjeksiyonu ile oluşturulan akut karaciğer hasarına karşı üzüm çekirdeği ekstresi ve kolşisinin etkisinin olmadığı kanaatine varıldı.

Anahtar Kelimeler: Kolşisin, Pentadekafluorooktanoik asit, rat, üzüm çekirdeği

References

  • Aydın, O., Yıldız, L., Kefeli, M., Barış, S., Kandemir, B., 2005. Kronik viral hepatitlerde ıshak modifiye histolojik aktivite indeksinin tek gözlemci ve gözlemciler arası tekrarlanabilirliği. Türk Patoloji Dergisi 21 (3-4), 58-61.
  • Bagchi, D., Bagchi, M., Stohs, J., Das, D., Ray, S., Kuszynski, C.A., Joshi, S.S., Pruess, H.G., 2000. Free radicals and grape seed proanthocyanidin extract: Importance in human health and disease prevention. Toxicology 148, 187-1
  • Bodenheimer, H., Schaffner, F., Pezzulo, J., 1998. Evalution of colchicine therapy in primary biliary cirrhosis. Journal of Gastroenterology 95, 124-129.
  • Bolarin, D.M., Barker, K., Fuller, G., 1987. Enzyme markers of collagen synthesis in carbon tetrachloride-induced fibrosis and during colchicine modification of CCI 4 induced liver injury. Experımental and Molecular Pathology 46, 145-152.
  • Bouhamidi, V., Prevost, V., Nouvelot, A., 1998. High protection by grape seed proanthocyanidins (GSPC) of polyunsaturated fatty acids against UV-C induced peroxidation. Life Sciences 321, 31Calafat, A.M., Wong, L.Y., Kuklenyik, Z., Reidy, J.A., Needham, L.L., 2007. Polyfluoroalkyl chemicals in the U.S. population: data from the National Health and Nutrition Examination Survey NHANES 2003-2004 and comparisons with NHANES 1999–2000. Environmental Health Perspectives 115 (11), 1596-1602.
  • Chahardehi, A.M., Ibrahim, D., Sulaiman, S.F., 200 Antioxidant activity and total phenolic content of some medicinal plants in Urticaceae family. Journal of Applied Biological Sciences 3, 25-29. Chen, L.C., Tatum, V., Glauert, H.P., Chow, C.K., 200 Peroxisome proliferator perfluorodecanoic acid alters glutathione and related enzymes. Journal of Biochemical and Molecular Toxicology 15, 107-112. Comporti, M., 1985. Biology of disease lipit peroxidation and cellular damage in toxic liver injury. Laboratory Investigation 53, 599-623.
  • Cui, L., Zhou, Q.F., Liao, C.Y., 2009. Studies on the toxicological effects of PFOA and PFOS on rats using histological observation and chemical analysis. Archives of Environmental Contamination and Toxicology 56 (2), 338-349. Cutrin, C., Menino, M.J., Carballo, C., Pazoj, A., Barrio, E., Parafita, M.A., 19 Lactacidaemia in rats with cirrhosis induced by carbon tetrachloride and ethanol: treaetment with colchicine, nifedipine and S-adenosyl methionine. Journal of Research in Medical Sciences 19, 351-352.
  • DePierre, J.W., 2002. Effects on rodents of perfluorofatty acids. In: Neilson, A.H. (Ed), The Handbook of Environmental Chemistry. Berlin, Springer-Verlag, pp. 203-248.
  • DuPont Haskell Laboratory, 1982. Excretion and disposition of 14C-ammonium perfluorooctanoate in male and female rats, mice, hamsters, and rabbits. US EPA Public Docket AR-226. US Environmental Protection Agency, Washington, DC.
  • Freeman, B., Crapo, J.D., 1982. Biology of disease, free radicals and tissue injury. Laboratory Investigation 47, 412-426.
  • Güllüoğlu, M.G., Özlük, Y., Öztürk, A.S., Demir, D., Çevikbaş, U., 2005. Viral hepatitlerin histolojik skorlamasında gözlemciler arası uyum. Türk Patoloji Dergisi 21 (1-2), 3-7.
  • Han, X., Kemper, R.A., Jepson, G.W., 2005. Subcellular distribution and protein binding of perfluorooctanoic acid in rat liver and kidney. Drug and Chemical Toxicology 28 (2), 19720
  • Hosokawa, M., Satoh, T., 1993. Differences in the induction of carboxylesterase isozymes in rat iver microsomes by perfluorinated fatty acids. Xenobiotica 23, 1125-1133.
  • İncioğlu, A., 2008. Kronik hepatit B’nin doğal seyri; ilerleyişi ve prognostik faktörler. Uzmanlık Tezi, T.C. Sağlık Bakanlığı Şişli Etfal Eğitim ve Araştırma Hastanesi Çocuk Sağlığı ve Hastalıkları Kliniği, İstanbul.
  • Kershenobich, D., Vargas, F., Garcia, G., Tamayo, R.P., Gent, M., Rojkind, M., 1988. Colchicine in the treatment of cirrhosis of the liver. New England Journal of Medicine 318, 1709-1713.
  • Kershenobisc, D., Rojkind, M., Quiroga, A.Q., Alcocer-Varela, J., 1990. Effect of colchicines on lymphocyte and monocyte function and its relation to fibroblast proliferation in primary biliary cirrhosis. Journal of Hepatology 9, 20520
  • Kudo, N., Sakai, A., Atsushi, M., Yasuhide, H., Tadashi, T., Yoichi, K., 2007. Tissue distribution and hepatic subcellular distribution of perfluorooctanoic acid at low dose are different from those at high dose in rats. Biological & Pharmaceutical Bulletin 30 (8), 1535-1540.
  • Larson, R.A., 1988. The antioxidants of higher plants. Phytochemistry 27, 969-978.
  • Lau, C., Anitole, K., Hodes, C., Lai, D., PfahlesHutchens A., Seed J., 2007. Perfluoroalkyl acids: a review of monitoring and toxicological findings. Toxicological Sciences 99 (2), 3663
  • Leighton, J.A., Bay, M.K., Maldonado, A.L., Johnson, R.F., Schenker, S., Speeg, K.V., 1990: The effect of liver dysfunction on colchicines pharmacokinetics in the rat. Journal of Hepatology 11, 210-215.
  • Leighton, J.A., Bay, M.K., Maldonado, A.L., Johnson, R.F., Schenker, S., Speeg, K.V., 19 Colchicine clearance is impaired in alcoholic cirrhosis. Journal of Hepatology 14, 1013-1015.
  • Menino, M.J., Cutrin, C., Parafita, M.A., 1993. Effect of colchicines on lactate production by isolated hepatocytes in rats treated with carbon tetrachloride and ethanol. Drug and Alcohol Dependence 32, 181-185.
  • Munoz, R.H., Munoz, M.D., Suarez, J., Sánchez, C.V., 1990. Adenosine partially prevents cirrhosis induced by carbon tetrachloride in rats. Journal of Hepatology 12, 242-248.
  • O’Brien, M.,L., Cunningham, M.,L., Spear, B.,T., Glauert, H.,P., 2001. Effects of peroxisome proliferators on glutathione and glutathione related enzymes in rats and hamsters. Toxicology and Applied Pharmacology 171, 27
  • O’Conner, J.J., 1988. Is colchicines effective therapy for cirrhosis. New England Journal of Medicine 318, 1751-1752.
  • Parola, M., Leonarduzzi, G., Biasi, F., Albano, E., Biocca, M.E., Poli, G., Dianzani, M.U., 1992. Vitamin E dietary supplemantion protects againist carbon tetrachloride induced chronic liver damage and cirrhosis. Journal of Hepatology 16, 1014-1021.
  • Pastoor, T.P., Lee, K.P., Perri, M.A., Gillies, P.J., 19 Biochemical and morphological studies of ammonium perfluorooctanoate-induced hepatomegaly and peroxisome proliferation. Experimental and Molecular Pathology 47, 98 Rojkind, M., Kershenobich, D., 1975. Effect of colchicines on collagen, albumin and transferring synthesis by cirrhotic rat liver slices. Acta Biochimica et Biophysica Sinica 378, 415-423.
  • Sabouraud, A., Rochdi, M., Urtizberea, M., Christen, M.O., Achtert, G., Scherrmann, J.M., 1992. Pharmacokinetics of colchicine: a review of experimental and clinical data. Gastroenterology 30 (1), 35-39.
  • Sato, M., Bagchi, D., Tosaki, A., Das, D., 2001. Grape seed proanthocyanidin reduces cardiomyocyte apoptosis by inhibiting ischemia/reperfusion-induced activation of JNK-1 anad C-JUN. Free Radical Biology and Medicine 31 (6), 729-737.
  • Seitz, H.K., Busenkell, R., Simanowski, U.A., Boesche, J., Kommerell, B., Rojkind, M., 19 Effect of colchicine on in vivo and in vitro ethanol metabolism in the rat. Gastroenterology 25, 270-273. Takagi, A., Sai, K., Umemura, T., Hasegawa, R., Kurokawa, Y., 1992. Hepatomegaly is an early biomarker for hepatocarcinogenesis induced by peroxisome proliferators. Journal of Environmental Pathology, Toxicology and Oncology 11 (3), 145-149.
  • Tebib, K., Rouanet, J., Besancon, P., 1997. Antioxidant effects of dietary polymeric grape seed tannins in tissues of rats fed a high cholesterol-vitamin E deficient diet. Food Chemistry 59 (1), 135-141.
  • Tribble, D.L., Jones, D.P., 1987. The pathological significance of lipit peroxidation in oxidative cell injury. Journal of Hepatology 7, 377-387.
  • U.S. Environmental Protection Agency, 2013. Perfluorooctanoic Acid (PFOA) and Fluorinated Telomers. http://www.epa.gov/oppt/pfoa/, (Erişim Tarihi: 17.01.2013).
  • Wang, D.,H., Ishii, K., Zhen, L.,X., Taketa, K,. 1996. Enhanced liver injury in acatalasemic mice following exposure to carbon tetrachloride. Archives of Toxicology 70, 189-194.
  • White, S.S., Fenton, S.E., Hines, E.P., 2011. Endocrine disrupting properties of perfluorooctanoic acid. Journal of Steroid
  • Biochemistry and Molecular Biology 127 (1-2), 16Ylinen, M., Kojo, A., Hanhijarvi, H., Peura, P., 19 Disposition of perfluooctanoic acid in the rat after single and subchronic administration. Bulletin of Environmental Contamination and Toxicology 44, 46-53.
There are 36 citations in total.

Details

Primary Language Turkish
Journal Section Research Article
Authors

Ayhan Atasever This is me

Duygu Yaman This is me

Akın Temel This is me

Publication Date July 22, 2014
Published in Issue Year 2014 Volume: 40 Issue: 2

Cite

APA Atasever, A., Yaman, D., & Temel, A. (2014). Ratlarda Pentadekafluorooktanoik Asit ile Oluşturulan Karaciğer Hasarı Üzerine Üzüm Çekirdeği ve Kolşisinin Etkisi. İstanbul Üniversitesi Veteriner Fakültesi Dergisi, 40(2), 191-201. https://doi.org/10.16988/iuvfd.45208
AMA Atasever A, Yaman D, Temel A. Ratlarda Pentadekafluorooktanoik Asit ile Oluşturulan Karaciğer Hasarı Üzerine Üzüm Çekirdeği ve Kolşisinin Etkisi. iuvfd. July 2014;40(2):191-201. doi:10.16988/iuvfd.45208
Chicago Atasever, Ayhan, Duygu Yaman, and Akın Temel. “Ratlarda Pentadekafluorooktanoik Asit Ile Oluşturulan Karaciğer Hasarı Üzerine Üzüm Çekirdeği Ve Kolşisinin Etkisi”. İstanbul Üniversitesi Veteriner Fakültesi Dergisi 40, no. 2 (July 2014): 191-201. https://doi.org/10.16988/iuvfd.45208.
EndNote Atasever A, Yaman D, Temel A (July 1, 2014) Ratlarda Pentadekafluorooktanoik Asit ile Oluşturulan Karaciğer Hasarı Üzerine Üzüm Çekirdeği ve Kolşisinin Etkisi. İstanbul Üniversitesi Veteriner Fakültesi Dergisi 40 2 191–201.
IEEE A. Atasever, D. Yaman, and A. Temel, “Ratlarda Pentadekafluorooktanoik Asit ile Oluşturulan Karaciğer Hasarı Üzerine Üzüm Çekirdeği ve Kolşisinin Etkisi”, iuvfd, vol. 40, no. 2, pp. 191–201, 2014, doi: 10.16988/iuvfd.45208.
ISNAD Atasever, Ayhan et al. “Ratlarda Pentadekafluorooktanoik Asit Ile Oluşturulan Karaciğer Hasarı Üzerine Üzüm Çekirdeği Ve Kolşisinin Etkisi”. İstanbul Üniversitesi Veteriner Fakültesi Dergisi 40/2 (July 2014), 191-201. https://doi.org/10.16988/iuvfd.45208.
JAMA Atasever A, Yaman D, Temel A. Ratlarda Pentadekafluorooktanoik Asit ile Oluşturulan Karaciğer Hasarı Üzerine Üzüm Çekirdeği ve Kolşisinin Etkisi. iuvfd. 2014;40:191–201.
MLA Atasever, Ayhan et al. “Ratlarda Pentadekafluorooktanoik Asit Ile Oluşturulan Karaciğer Hasarı Üzerine Üzüm Çekirdeği Ve Kolşisinin Etkisi”. İstanbul Üniversitesi Veteriner Fakültesi Dergisi, vol. 40, no. 2, 2014, pp. 191-0, doi:10.16988/iuvfd.45208.
Vancouver Atasever A, Yaman D, Temel A. Ratlarda Pentadekafluorooktanoik Asit ile Oluşturulan Karaciğer Hasarı Üzerine Üzüm Çekirdeği ve Kolşisinin Etkisi. iuvfd. 2014;40(2):191-20.