Editöre Mektup
Radioprotective effect of montelukast sodium against hepatic radioiodine (131I) toxicity: A histopathological investigation in the rat model
Yıl 2015, Cilt: 62 Sayı: 1, 37 - 43, 01.03.2015Öz
Radioactive iodine (131I) is a known radionuclide which is used both for diagnostic and therapeutic purposes in the treatment of hyperthyroidism and thyroid cancer. Montelukast sodium (Cysteinyl leukotriene receptor-1 antagonist) is also a wellknown antioxidant drug. This study aimed to evaluate the histopathological changes in rat livers at the third month following 131I treatment and the radioprotective effect of Montelukast sodium (ML) against 131I-related liver damage. Thirty female Wistar Albino rats were randomly divided into three groups as control group (n=10), untreated rats; second (RAI) group (n=10), oral radioiodine (111 MBq) administrated rats, and third (ML) group (n=10), oral radioiodine and ML administrated rats. In the third group, ML administration was started 3 days before and ended 10 days after RAI administration. In the third month of radioiodine (RAI) administration, the animals were decapitated and the livers were removed for histopathological examination. The histopathologic data were evaluated comparatively by using Mann Whitney U and Fisher’s Exact Tests Differences were determined in all the parameters in terms of intensity between the control and 131I groups, which showed the harmful effects of 131I. In the comparison of the 131I and ML groups, hyperemia was determined respectively 80% to 40%, the presence of inflammatory cells 70% to 60% and capsule thickening 70% to 40%. Montelukast sodium was observed to have a protective effect especially on hyperemia and capsule thickening. According to the study results, radioactive iodine (131I) treatment seems to cause morphological damage to the rat liver, and Montelukast sodium effectively protects the liver against damage
Anahtar Kelimeler
Kaynakça
- Acar U, Atilgan HI, Acar DE, Akaya ZY, Yumusak N, Korkmaz M, Koca G (2013): The effect of short-term vitamin E against radioiodine-induced early lacrimal gland damage. Ann Nucl Med, DOI 10.1007/s12149-013- 0763-z.
- Albert MD, Bucher NL (1960): Latent injury and repair in rat liver induced to regenerate at intervals after x- radiation. Cancer Res, 20: 1514-1522.
- Alexander C, Bader JB, Schaefer A, Finke C, Kirsch CM (1998): Intermediate and long-term side effects of high-dose radioiodine therapy for thyroid carcinoma. J Nucl Med, 39: 1551-1554.
- Arora R, Gupta D, Chawla R, Sagar R, Sharma A, Kumar R, Prasad J, Singh S, Samanta N, Sharma RK (2005): Radioprotection by plant products: present status and future prospects. Phytother Res, 19: 1-22.
- Beytur A, Ciftci O, Oguz F, Oguzturk H, Yilmaz F (2012): Montelukast attenuates side effects of cisplatin including testicular, spermatological, and hormonal damage in male rats. Cancer Chemother Pharmacol, 69: 207-213.
- Bhartiya US, Raut YS, Joseph LJ, Hawaldar RW, Rao BS (2008): Evaluation of the radioprotective effect of turmeric extract and vitamin E in mice exposed to therapeutic dose of radioiodine. Indian J Clin Biochem, 23: 382-386.
- Bohuslavizki KH, Klutmann S, Jenicke L, Brenner W, Feyerabend B, Henze E, Clausen M (1999): Radioprotection of salivary glands by S-2- (3aminopropylamino)-ethylphosphorothioic (amifostine) obtained in a rabbit animal model. Int J Radiat Oncol Biol Phys, 45: 181-186.
- Brown-Grant K (1961): Extrathyroidal iodide concentrating mechanisms. Physiol Rev, 41: 189-213.
- Capizzi RL, Oster W (2000): Chemoprotective and radioprotective effects of amifostine: an update of clinical trials. Int J Hematol, 72: 425-435.
- Carrasco N (1993): Iodide transport in the thyroid gland. Biochim Biophys Acta, 1154: 65-82.
- Goolden AWG, Mallard JR. Farran HE (1957): Radiation sialitis following radioiodine therapy. Br J Radiol, 30: 210-212.
- Guha C, Sharma A, Gupta S, Alfieri A, Gorla GR, Gagandeep S, Sokhi R, Roy-Chowdhury N, Tanaka KE, Vikram B, Roy-Chowdhury J (1999): Amelioration of radiation-induced liver damage in partially hepatectomized rats by hepatocyte transplantation. Cancer Res, 59: 5871-5874.
- Gultekin FA, Bakkal BH, Guven B, Tasdoven I, Bektas S, Can M, Comert M (2013): Effects of ozone oxidative preconditioning on radiation-induced organ damage in rats. J Radiat Res, 54: 36-44.
- Hibbert A, Gruffydd-Jones T, Barrett EL, Day MJ, Harvey AM (2009): Feline thyroid carcinoma: diagnosis and response to high-dose radioactive iodine treatment. Journal of Feline Medicine and Surgery, 11: 116-124.
- Koc M, Taysi S, Buyukokuroglu ME, Bakan N (2003): Melatonin protects rat liver against irradiation-induced oxidative injury. J Radiat Res, 44: 211-215.
- Koca G, Gültekin SS, Han U, Kuru S, Demirel K, Korkmaz M (2013): The efficacy of montelukast as a protective agent against 131I-induced salivary gland damage in rats: scintigraphic and histopathological findings. Nucl Med Commun, 34: 507-517.
- Koca G, Yalniz-Akkaya Z, Gultekin SS, Yumusak N, Demirel K, Korkmaz M, Atilgan HI, Altinparmak UE, Onal B, Ornek F (2013): Radioprotective effect of montelukast sodium in rat lacrimal glands after radioiodine treatment. Rev Esp Med Nucl Imagen Mol, 32: 294-300.
- Liptak JM (2007): Canine Thyroid Carcinoma. Clin Tech Small Anim Pract, 22: 75-81.
- Liu B, Kuang A, Huang R, Zhao Z, Zeng Y, Wang J, Tian R (2010): Influence of vitamin C on salivary absorbed dose of 131I in thyroid cancer patients: a prospective, randomized, single-blind, controlled trial. J Nucl Med, 51: 618-623.
- Mohamadin AM, Elberry AA, Elkablawy MA, Gawad HS, Al-Abbasi FA (2011): Montelukast, a leukotriene receptor antagonist abrogates lipopolysaccharide-induced toxicity and oxidative stress in rat liver. Pathophysiology, 18: 235-242.
- Nascimento AC, Lipsztein JL, Corbo R, Rebelo AM (2010): 131I Biokinetics and cytogenetic dose estimates in ablation treatment of thyroid carcinoma. Health Phys, 99: 457-463.
- Omur O, Akgun A, Ozcan Z, Sen C, Ozkılıç H (2009): Clinical implications of diffuse hepatic uptake observed in postablative and post-therapeutic I-131 scans. Clin Nucl Med, 34: 11-14.
- Ozkan E, Yardimci S, Dulundu E, Topaloğlu U, Sehirli O, Ercan F, Velioglu-Ogunc A, Sener G (2010): Protective potential of montelukast against hepatic ischemia/reperfusion injury in rats. J Surg Res, 159: 588- 594.
- Peremans K, Vandermeulen E, Van Hoek I, Daminet S, Vermeire S, Bacher K (2008): Interference of iohexol with radioiodine thyroid uptake in the hyperthyroid cat. Journal of Feline Medicine and Surgery, 10: 460-465.
- Peterson ME (2006): Radioiodine Treatment of Hyperthyroidism. Clin Tech Small Anim Pract, 21: 34-39.
- Riesco-Eizaguirre G, Santisteban P (2006): A perspective view of sodium iodide symporter research and its clinical implications. Eur J Endocrinol, 155: 495-512.
- Sener G, Sehirli O, Cetinel S, Ercan F, Yuksel M, Gedik N, et al. (2005): Amelioration of sepsis-induced hepatic and ileal injury in rats by the leukotriene receptor blocker montelukast. Prostaglandins Leukot Essent Fatty Acids, 73: 453-62.
- Silberstein EB (2008): Reducing the incidence of 131I- induced sialadenitis: the role of pilocarpine. J Nucl Med, 49: 546-549.
- Srinivasan M, Sudheer AR, Pillai KR, Kumar PR, Sudhakaran PR, Menon VP (2006): Influence of ferulic acid on gamma-radiation induced DNA damage, lipid peroxidation and antioxidant status in primary culture of isolated rat hepatocytes. Toxicology, 228: 249-258.
- Srinivasan M, Sudheer AR, Pillai KR, Kumar PR, Sudhakaran PR, Menon VP (2007): Modulatory effects of curcumin on γ-radiation-induced cellular damage in primary culture of isolated rat hepatocytes. Environ Toxicol Pharmacol, 24: 98-105.
- Takasaki J, Kamohara M, Matsumoto M, Saito T, Sugimoto T, Ohishi T, et al. (2000): The molecular characterization and tissue distribution of the human cysteinyl leukotriene CysLT(2) receptor. Biochem Biophys Res Commun, 274: 316-22.
- Wyszomirska A (2012): Iodine-131 for therapy of thyroid diseases. Physical and biological basis. Nucl Med Rev Cent East Eur, 15: 120-123.
Karaciğerde radyoiodin (131İ) toksisitesine karşı montelukast sodyumun radyoprotektif etkisi: Ratmodelinde histopatolojik incelemeler
Yıl 2015, Cilt: 62 Sayı: 1, 37 - 43, 01.03.2015Öz
Radyoaktif iyot (131I) hipertiroidizm ve tiroid kanserlerinin tanı ve tedavisi amacıyla kullanılan bir radyonükliddir. Montelukast sodyum (Cysteinyl leukotriene receptor-1 inhibitörü) ise antioksidan olarak bilinen bir ilaçtır. Bu çalışma ile rat karaciğerinde radyoiodinden (RAI) kaynaklanan radyasyon hasarına karşı Montelukast sodyumun (ML) radyoprotektif etkisinin histopatolojik olarak değerlendirilmesi amaçlandı. Çalışmada 30 adet dişi Wistar Albino rat kullanıldı ve bunlar rastgele üç gruba ayrıldı; birinci grubu hiçbir işleme tabi tutulmayan kontrol grubu (n=10), ikinci (RAI) grubu, (n=10), oral olarak RAI (111 MBq) uygulanan ratlar, üçüncü (ML) grubunu ise (n=10) oral olarak RAI ve ML uygulanan grup oluşturdu. Üçüncü çalışma grubunda ML uygulaması RAI uygulamasından 3 gün önce başlatıldı ve 10 gün sonra bitirildi. Üçüncü ay sonunda nekropsileri yapılan ratların karaciğer doku örnekleri rutin doku takibine alınarak histopatolojik olarak incelendi. Radyoiodin ve ML grubunda tüm histopatolojik bulgular Mann Whitney U testi ve Fisher’in ekzak test ile karşılaştırılarak değerlendirildi. Bütün parametreler açısından, RAI’un zararlı etkisini gösterecek şekilde, kontrol ve RAI grubu arasında insidans açısından farklılık vardı. Radyoiodin ve ML grubunun karşılaştırmasında, parametrelerin insidansı hiperemi açısından sırasıyla %80’e %40, inflamatuar hücre varlığı %70’e %60, kapsül kalınlaşması %70’e %40 idi. Montelukastın özellikle hiperemi ve kapsül kalınlaşması açısından koruyucu etkisi olduğu görüldü. Montelukast sodyumun RAI tedavisi sonrası karaciğerde özellikle hiperemi ve kapsül kalınlaşması üzerine parsiyel radyoprotektif etkisi olduğu belirlendi
Anahtar Kelimeler
İodine-131, histopatoloji, karaciğer, montelukast sodyum, rat
Kaynakça
- Acar U, Atilgan HI, Acar DE, Akaya ZY, Yumusak N, Korkmaz M, Koca G (2013): The effect of short-term vitamin E against radioiodine-induced early lacrimal gland damage. Ann Nucl Med, DOI 10.1007/s12149-013- 0763-z.
- Albert MD, Bucher NL (1960): Latent injury and repair in rat liver induced to regenerate at intervals after x- radiation. Cancer Res, 20: 1514-1522.
- Alexander C, Bader JB, Schaefer A, Finke C, Kirsch CM (1998): Intermediate and long-term side effects of high-dose radioiodine therapy for thyroid carcinoma. J Nucl Med, 39: 1551-1554.
- Arora R, Gupta D, Chawla R, Sagar R, Sharma A, Kumar R, Prasad J, Singh S, Samanta N, Sharma RK (2005): Radioprotection by plant products: present status and future prospects. Phytother Res, 19: 1-22.
- Beytur A, Ciftci O, Oguz F, Oguzturk H, Yilmaz F (2012): Montelukast attenuates side effects of cisplatin including testicular, spermatological, and hormonal damage in male rats. Cancer Chemother Pharmacol, 69: 207-213.
- Bhartiya US, Raut YS, Joseph LJ, Hawaldar RW, Rao BS (2008): Evaluation of the radioprotective effect of turmeric extract and vitamin E in mice exposed to therapeutic dose of radioiodine. Indian J Clin Biochem, 23: 382-386.
- Bohuslavizki KH, Klutmann S, Jenicke L, Brenner W, Feyerabend B, Henze E, Clausen M (1999): Radioprotection of salivary glands by S-2- (3aminopropylamino)-ethylphosphorothioic (amifostine) obtained in a rabbit animal model. Int J Radiat Oncol Biol Phys, 45: 181-186.
- Brown-Grant K (1961): Extrathyroidal iodide concentrating mechanisms. Physiol Rev, 41: 189-213.
- Capizzi RL, Oster W (2000): Chemoprotective and radioprotective effects of amifostine: an update of clinical trials. Int J Hematol, 72: 425-435.
- Carrasco N (1993): Iodide transport in the thyroid gland. Biochim Biophys Acta, 1154: 65-82.
- Goolden AWG, Mallard JR. Farran HE (1957): Radiation sialitis following radioiodine therapy. Br J Radiol, 30: 210-212.
- Guha C, Sharma A, Gupta S, Alfieri A, Gorla GR, Gagandeep S, Sokhi R, Roy-Chowdhury N, Tanaka KE, Vikram B, Roy-Chowdhury J (1999): Amelioration of radiation-induced liver damage in partially hepatectomized rats by hepatocyte transplantation. Cancer Res, 59: 5871-5874.
- Gultekin FA, Bakkal BH, Guven B, Tasdoven I, Bektas S, Can M, Comert M (2013): Effects of ozone oxidative preconditioning on radiation-induced organ damage in rats. J Radiat Res, 54: 36-44.
- Hibbert A, Gruffydd-Jones T, Barrett EL, Day MJ, Harvey AM (2009): Feline thyroid carcinoma: diagnosis and response to high-dose radioactive iodine treatment. Journal of Feline Medicine and Surgery, 11: 116-124.
- Koc M, Taysi S, Buyukokuroglu ME, Bakan N (2003): Melatonin protects rat liver against irradiation-induced oxidative injury. J Radiat Res, 44: 211-215.
- Koca G, Gültekin SS, Han U, Kuru S, Demirel K, Korkmaz M (2013): The efficacy of montelukast as a protective agent against 131I-induced salivary gland damage in rats: scintigraphic and histopathological findings. Nucl Med Commun, 34: 507-517.
- Koca G, Yalniz-Akkaya Z, Gultekin SS, Yumusak N, Demirel K, Korkmaz M, Atilgan HI, Altinparmak UE, Onal B, Ornek F (2013): Radioprotective effect of montelukast sodium in rat lacrimal glands after radioiodine treatment. Rev Esp Med Nucl Imagen Mol, 32: 294-300.
- Liptak JM (2007): Canine Thyroid Carcinoma. Clin Tech Small Anim Pract, 22: 75-81.
- Liu B, Kuang A, Huang R, Zhao Z, Zeng Y, Wang J, Tian R (2010): Influence of vitamin C on salivary absorbed dose of 131I in thyroid cancer patients: a prospective, randomized, single-blind, controlled trial. J Nucl Med, 51: 618-623.
- Mohamadin AM, Elberry AA, Elkablawy MA, Gawad HS, Al-Abbasi FA (2011): Montelukast, a leukotriene receptor antagonist abrogates lipopolysaccharide-induced toxicity and oxidative stress in rat liver. Pathophysiology, 18: 235-242.
- Nascimento AC, Lipsztein JL, Corbo R, Rebelo AM (2010): 131I Biokinetics and cytogenetic dose estimates in ablation treatment of thyroid carcinoma. Health Phys, 99: 457-463.
- Omur O, Akgun A, Ozcan Z, Sen C, Ozkılıç H (2009): Clinical implications of diffuse hepatic uptake observed in postablative and post-therapeutic I-131 scans. Clin Nucl Med, 34: 11-14.
- Ozkan E, Yardimci S, Dulundu E, Topaloğlu U, Sehirli O, Ercan F, Velioglu-Ogunc A, Sener G (2010): Protective potential of montelukast against hepatic ischemia/reperfusion injury in rats. J Surg Res, 159: 588- 594.
- Peremans K, Vandermeulen E, Van Hoek I, Daminet S, Vermeire S, Bacher K (2008): Interference of iohexol with radioiodine thyroid uptake in the hyperthyroid cat. Journal of Feline Medicine and Surgery, 10: 460-465.
- Peterson ME (2006): Radioiodine Treatment of Hyperthyroidism. Clin Tech Small Anim Pract, 21: 34-39.
- Riesco-Eizaguirre G, Santisteban P (2006): A perspective view of sodium iodide symporter research and its clinical implications. Eur J Endocrinol, 155: 495-512.
- Sener G, Sehirli O, Cetinel S, Ercan F, Yuksel M, Gedik N, et al. (2005): Amelioration of sepsis-induced hepatic and ileal injury in rats by the leukotriene receptor blocker montelukast. Prostaglandins Leukot Essent Fatty Acids, 73: 453-62.
- Silberstein EB (2008): Reducing the incidence of 131I- induced sialadenitis: the role of pilocarpine. J Nucl Med, 49: 546-549.
- Srinivasan M, Sudheer AR, Pillai KR, Kumar PR, Sudhakaran PR, Menon VP (2006): Influence of ferulic acid on gamma-radiation induced DNA damage, lipid peroxidation and antioxidant status in primary culture of isolated rat hepatocytes. Toxicology, 228: 249-258.
- Srinivasan M, Sudheer AR, Pillai KR, Kumar PR, Sudhakaran PR, Menon VP (2007): Modulatory effects of curcumin on γ-radiation-induced cellular damage in primary culture of isolated rat hepatocytes. Environ Toxicol Pharmacol, 24: 98-105.
- Takasaki J, Kamohara M, Matsumoto M, Saito T, Sugimoto T, Ohishi T, et al. (2000): The molecular characterization and tissue distribution of the human cysteinyl leukotriene CysLT(2) receptor. Biochem Biophys Res Commun, 274: 316-22.
- Wyszomirska A (2012): Iodine-131 for therapy of thyroid diseases. Physical and biological basis. Nucl Med Rev Cent East Eur, 15: 120-123.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Veteriner Cerrahi |
| Diğer ID | JA22EE52RU |
| Bölüm | Araştırma Makalesi |
| Yazarlar |
|
| Yayımlanma Tarihi | 1 Mart 2015 |
| Yayınlandığı Sayı | Yıl 2015Cilt: 62 Sayı: 1 |
Kaynak Göster
| Bibtex | @editöre mektup { auvfd532436, journal = {Ankara Üniversitesi Veteriner Fakültesi Dergisi}, issn = {1300-0861}, eissn = {1308-2817}, address = {}, publisher = {Ankara Üniversitesi}, year = {2015}, volume = {62}, number = {1}, pages = {37 - 43}, doi = {10.1501/Vetfak\_0000002655}, title = {Radioprotective effect of montelukast sodium against hepatic radioiodine (131I) toxicity: A histopathological investigation in the rat model}, key = {cite}, author = {Atılgan, Hasan İkbal and Yumuşak, Nihat and Sadıc, Murat and Gultekın, Salih Sinan and Koca, Gokhan and Ozyurt, Sinem and Demırel, Koray and Korkmaz, Meliha} } |
| APA | Atılgan, H. İ. , Yumuşak, N. , Sadıc, M. , Gultekın, S. S. , Koca, G. , Ozyurt, S. , Demırel, K. & Korkmaz, M. (2015). Radioprotective effect of montelukast sodium against hepatic radioiodine (131I) toxicity: A histopathological investigation in the rat model . Ankara Üniversitesi Veteriner Fakültesi Dergisi , 62 (1) , 37-43 . DOI: 10.1501/Vetfak_0000002655 |
| MLA | Atılgan, H. İ. , Yumuşak, N. , Sadıc, M. , Gultekın, S. S. , Koca, G. , Ozyurt, S. , Demırel, K. , Korkmaz, M. "Radioprotective effect of montelukast sodium against hepatic radioiodine (131I) toxicity: A histopathological investigation in the rat model" . Ankara Üniversitesi Veteriner Fakültesi Dergisi 62 (2015 ): 37-43 <http://vetjournal.ankara.edu.tr/tr/pub/issue/43549/532436> |
| Chicago | Atılgan, H. İ. , Yumuşak, N. , Sadıc, M. , Gultekın, S. S. , Koca, G. , Ozyurt, S. , Demırel, K. , Korkmaz, M. "Radioprotective effect of montelukast sodium against hepatic radioiodine (131I) toxicity: A histopathological investigation in the rat model". Ankara Üniversitesi Veteriner Fakültesi Dergisi 62 (2015 ): 37-43 |
| RIS | TY - JOUR T1 - Karaciğerde radyoiodin (131İ) toksisitesine karşı montelukast sodyumun radyoprotektif etkisi: Ratmodelinde histopatolojik incelemeler AU - Hasan İkbalAtılgan, NihatYumuşak, MuratSadıc, Salih SinanGultekın, GokhanKoca, SinemOzyurt, KorayDemırel, MelihaKorkmaz Y1 - 2015 PY - 2015 N1 - doi: 10.1501/Vetfak_0000002655 DO - 10.1501/Vetfak_0000002655 T2 - Ankara Üniversitesi Veteriner Fakültesi Dergisi JF - Journal JO - JOR SP - 37 EP - 43 VL - 62 IS - 1 SN - 1300-0861-1308-2817 M3 - doi: 10.1501/Vetfak_0000002655 UR - https://doi.org/10.1501/Vetfak_0000002655 Y2 - 2023 ER - |
| EndNote | %0 Ankara Üniversitesi Veteriner Fakültesi Dergisi Radioprotective effect of montelukast sodium against hepatic radioiodine (131I) toxicity: A histopathological investigation in the rat model %A Hasan İkbal Atılgan , Nihat Yumuşak , Murat Sadıc , Salih Sinan Gultekın , Gokhan Koca , Sinem Ozyurt , Koray Demırel , Meliha Korkmaz %T Radioprotective effect of montelukast sodium against hepatic radioiodine (131I) toxicity: A histopathological investigation in the rat model %D 2015 %J Ankara Üniversitesi Veteriner Fakültesi Dergisi %P 1300-0861-1308-2817 %V 62 %N 1 %R doi: 10.1501/Vetfak_0000002655 %U 10.1501/Vetfak_0000002655 |
| ISNAD | Atılgan, Hasan İkbal , Yumuşak, Nihat , Sadıc, Murat , Gultekın, Salih Sinan , Koca, Gokhan , Ozyurt, Sinem , Demırel, Koray , Korkmaz, Meliha . "Radioprotective effect of montelukast sodium against hepatic radioiodine (131I) toxicity: A histopathological investigation in the rat model". Ankara Üniversitesi Veteriner Fakültesi Dergisi 62 / 1 (Mart 2015): 37-43 . https://doi.org/10.1501/Vetfak_0000002655 |
| AMA | Atılgan H. İ. , Yumuşak N. , Sadıc M. , Gultekın S. S. , Koca G. , Ozyurt S. , Demırel K. , Korkmaz M. Radioprotective effect of montelukast sodium against hepatic radioiodine (131I) toxicity: A histopathological investigation in the rat model. Ankara Univ Vet Fak Derg. 2015; 62(1): 37-43. |
| Vancouver | Atılgan H. İ. , Yumuşak N. , Sadıc M. , Gultekın S. S. , Koca G. , Ozyurt S. , Demırel K. , Korkmaz M. Radioprotective effect of montelukast sodium against hepatic radioiodine (131I) toxicity: A histopathological investigation in the rat model. Ankara Üniversitesi Veteriner Fakültesi Dergisi. 2015; 62(1): 37-43. |
| IEEE | H. İ. Atılgan , N. Yumuşak , M. Sadıc , S. S. Gultekın , G. Koca , S. Ozyurt , K. Demırel ve M. Korkmaz , "Radioprotective effect of montelukast sodium against hepatic radioiodine (131I) toxicity: A histopathological investigation in the rat model", Ankara Üniversitesi Veteriner Fakültesi Dergisi, c. 62, sayı. 1, ss. 37-43, Mar. 2015, doi:10.1501/Vetfak_0000002655 |