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Farmakolojik Araştırmalarda Hayvan Deneyleri Tasarımı

Yıl 2024, Cilt: 26 Sayı: S1
https://doi.org/10.18678/dtfd.1489639

Öz

İlaç bilimi olarak adlandırılan farmakoloji özellikle 20. yüzyılda çok önemli bir ilerleme kaydederek günümüz modern ilaçlarının geliştirilmesinde temel rol almıştır. Farmakoloji ilaç gelişiminde in vitro, in vivo ve klinik araştırma basamaklarından yararlanmaktadır. Bunların içerisinde bulunan in vivo araştırmalarda ise deney hayvanlarının önemi büyüktür. Günümüzde kullanılan ilaçların büyük çoğunluğu deney hayvanları araştırmaları sayesinde geliştirilmişlerdir. Deney hayvanlarının kullanılacağı araştırmalar, öznenin canlı bir varlık olması nedeniyle dikkatli planlanmalı ve asgari sayıda hayvan kullanımı sağlanmalıdır. Bunun yanı sıra deneyler sırasında da hayvanlara gereksiz yere eziyet ve acı verebilecek işlemlerden kaçınılması en önemli etik ilkelerdendir. Farmakolojik araştırmaların amacı hastalıklara karşı tedavi veya tanı amacıyla ilaç geliştirmektir. Bu nedenle araştırılan maddenin hastalık varlığında etkilerini tespit etmek amaçlanmaktadır. Daha önce insanlarda etkileri bilinmeyen bir maddenin hemen insanlarda kullanılması çeşitli olumsuzluklara hatta ölümlere yol açabilecektir. Geçmişte yaşanan pek çok olay sonrasında ilaç geliştirme aşamaları uluslararası kabul edilen kurallar ile belirlenmiştir. Bu kurallara göre araştırılan maddenin etkisinin insanlardan önce hastalık modeli oluşturulmuş deney hayvanlarında araştırılması gerekmektedir. Bu amaçla geliştirilmiş pek çok hastalık modeli oluşturulmuştur. Deney hayvanlarında oluşturulan bu hastalık modellerinde geliştirilen pek çok ilaç günümüzde başarı ile insanların tedavisinde kullanılmaktadır.

Kaynakça

  • Jota Baptista CV, Faustino-Rocha AI, Oliveria PA. Animal models in pharmacology: a brief history awarding the Nobel prizes for physiology or medicine. Pharmacology. 2021;106(7-8):356-68.
  • Altun A, Keskin İ. Ethical status and rules for selecting models in animal studies. Sakarya Med J. 2020;10(2):359-64. Turkish.
  • Johnson PD, Besselsen DG. Practical aspects of experimental design in animal research. ILAR J. 2002;43(4):202-6.
  • Yarsan E, editor. Veteriner hekimlikte ilaç uygulama yöntemleri. Ankara: Nobel Kitabevleri; 2019. Turkish.
  • Bora ES, Özlü C. Klinik bilimlerde deney hayvani modelleri. Ankara: Akademisyen Kitabevi. 2020. Turkish.
  • Senio M. Classification criteria of epileptic seizures and syndromes. Epilepsy Res. 2006;70(Suppl 1):S27-33.
  • Marangoz C. Experimental models of epilepsy. J Exp Clin Med. 1997;14(3):147-86. Turkish.
  • McCandless DW, FineSmith RB. Chemically induced model of seizures. In: Boulton AA, Baker GB, Butterworth RF, editors. Animal models of neurological disease, II. Neuromethods, Vol 22. Totowa, NJ: Humana Press; 1992. p.133-51.
  • Miromoto K, Fahnestock M, Racine RJ. Kindling and status epilepticus model of epilepsy: rewiring the brain. Prog Neurobiol. 2004;73(1):1-60.
  • Pitkanen A, Schwartzkroin PA, Moshe SL, editors. Models of seizures and epilepsy. USA: Elsevier Academic Press; 2006.
  • Korkmaz Ü, Kaya M. Experimental models in neurodegenerative diseases. Nucl Med Semin. 2019;5(1):69-77. Turkish.
  • Do Carmo S, Cuello AC. Modeling Alzheimer’s disease in transgenic rats. Mol Neurodegener. 2013;8:37.
  • Elçioğlu HK, Yılmaz G, İlhan B, Karan MA. Experimental animal models for Alzheimer disease. Nobel Med. 2018;14(1):5-13. Turkish.
  • Gubellini P, Kachidian P. Animal models of Parkinson’s disease: An updated overview. Rev Neurol (Paris). 2015;171(11):750-61.
  • Martineau E, Di Polo A, Vande Velde C, Robitaille R. Dynamic neuromuscular remodeling precedes motor-unit loss in a Mouse model of ALS. eLife. 2018;7:e41973.
  • Hao Y, Ge H, Sun M, Gao Y. Selecting an appropriate animal model of depression. Int J Mol Sci. 2019;20(19):4827.
  • Kobeissy FH, editor. Psychiatric disorders: methods and protocols. Totowa, NJ: Humana Press; 2012.
  • Wang Q, Timberlake MA 2nd, Prall K, Dwivedi Y. The recent progress in animal models of depression. Prog Neuropsychopharmacol Biol Psychiatry. 2017;77:99-109.
  • Valvassori SS, Budni J, Varela RB, Quevedo J. Contributions of animal models to the study of mood disorders. Braz J Psychiatry. 2013;35(Suppl 2):S121-31.
  • Padilla E, Barret D, Shumake J, Gonzales-Lima F. Strain, sex and open-field behavior: factors underlying the genetic susceptibility to helplessness. Behav Brain Res. 2009;201(2):257-64.
  • Nam H, Clinton SM, Jackson NL, Kerman IA. Learned helplessness and social avoidance in the Wistar-Kyoto rat. Front Behav Neurosci. 2014;8:109.
  • Powell SB. Models of neurodevelopmental abnormalities in schizophrenia. Curr Top Behav Neurosci. 2010;4:435-81.
  • Tsai G, Coyle JT. Glutamatergic mechanisms in schizophrenia. Annu Rev Pharmacol Toxicol. 2002;42:165-79.
  • Clapcote S, Lipina TV, Millar JK, Mackie S, Christie S, Ogawa F, et al. Behavioral phenotypes of Disc1 missense mutations in mice. Neuron. 2007;54(3):387-402.
  • Basset AS, Chow EW. Schizophrenia and 22q11.2 deletion syndrome. Curr Psyciatry Rep. 2008;10(2):148-57.
  • Uzbay İT. Experimental animal models used in substance addiction studies. Madde bağımlılığı çalışmalarında kullanılan deneysel hayvan modelleri. MİSED. 2009;21-22:49-63. Turkish.
  • Becker JAJ, Kieffer BL, Le Merrer J. Differential behavioral and molecular alterations upon protracted abstinence from cocaine versus morphine, nicotine, THC and alcohol. Addict Biol. 2017;22(5):1205-17.
  • Vanderschuren LJMJ, Minnaard AM, Smeets JAS, Lesscher HMB. Punishment models of addictive behavior. Curr Opin Behav Sci. 2017;13:77-84.
  • Zicha J, Kunes J, Lébl M, Pohlová I, Slaninová J, Jelínek J. Antidiuretic and pressor actions of vasopressin in age-dependent DOCA-salt hypertension. Am J Physiol. 1989;256(1 Pt 2):138-45.
  • Prager-Khoutorsky M, Choe KY, Levi DI, Bourque CW. Role of vasopressin in rat models of salt-dependent hypertension. Curr Hypertens Rep. 2017;19(5):42.
  • Dobrian AD, Davies MJ, Prewitt RL, Lauterio TJ. Development of hypertension in a rat model of diet-induced obesity. Hypertension. 2000;35(4):1009-15.
  • Juskevich JC, Robinson DS, Whitehorn D. Effect of hypothalamic stimulation in spontaneously hypertensive and Wistar-Kyoto rats. Eur J Pharmacol. 1978;51(4):429-39.
  • Bomfim GF, Dos Santos RA, Oliveira MA, Giachini FR, Akamine EH, Tostes RC, et al. Toll-like receptor 4 contributes to blood pressure regulation and vascular contraction in spontaneously hypertensive rats. Clin Sci (Lond). 2012;122(11):535-43.
  • Shikalgar TS, Naikwade NS. Evaluation of cardioprotective activity of fulvic acid against isoproterenol induced oxidative damage in rat myocardium. Int Res J Pharm. 2018;9(1):71-80.
  • Wang J, Bo H, Meng X, Wu Y, Bao Y, Li Y. A simple and fast experimental model of myocardial infarction in the mouse. Texas Heart Inst J. 2006;33(3):290-3.
  • Isorni MA, Casanova A, Piquet J, Bellamy V, Pignon C, Puymirat E, et al. Comparative analysis of methods to induce myocardial infarction in a closed-chest rabbit model. Biomed Res Int. 2015;2015:893051.
  • Zhou S, Wright JL, Liu J, Sin DD, Churg A. Aging does not enhance experimental cigarette smoke-induced COPD in the mouse. PLoS One. 2013;8(8):e71410.
  • Vernooy JH, Dentener MA, van Suylen RJ, Buurman WA, Wouters EF. Long-term intratracheal lipopolysaccharide exposure in mice results in chronic lung inflammation and persistent pathology. Am J Respir Cell Mol Biol. 2002;26(1):152-9.
  • Pera T, Zuidhof A, Valadas J, Smit M, Schoemaker RG, Gosens R, et al. Tiotropium inhibits pulmonary inflammation and remodelling in a guinea pig model of COPD. Eur Respir J. 2011;38(4):789-96.
  • Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology. 1990;98(3):694-702.
  • Neurath MF, Fuss I, Kelsall BL, Stüber E, Strober W. Antibodies to interleukin 12 abrogate established experimental colitis in mice. J Exp Med. 1995;182(5):1281-90.
  • Souza MH, Mota JM, Oliveira RB, Cunha FQ. Gastric damage induced by different doses of indomethacin in rats is variably affected by inhibiting iNOS or leukocyte infiltration. Inflamm Res. 2008;57(1):28-33.
  • Lenzen S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia. 2008;51(2):216-26.
  • Mathews CE. Utility of murine models for the study of spontaneous autoimmune type 1 diabetes. Pediatr Diabetes. 2005;6(3):165-77.
  • Jun HS, Yoon JW. The role of viruses in type 1 diabetes: two distinct cellular and molecular pathogenic mechanisms of virus-induced diabetes in animals. Diabetologia. 2001;44(3):271-85.
  • Allen TJ, Cooper ME, Lan HY. Use of genetic mouse models in the study of diabetic nephropathy. Curr Diab Rep. 2004;4(6):435-40.
  • Pickup JC, Williams G, editors. Textbook of diabetes, 2nd ed. Cambridge, MA: Blackwell Science; 1997.
  • Kim JH, Saxton AM. The TALLYHO mouse as a model of human type 2 diabetes. Methods Mol Biol. 2012;933:75-87.
  • Almosailleakh M, Schwaller J. Murine models of acute myeloid leukaemia. Int J Mol Sci. 2019;20(2):453.
  • Hastings RH, Burton DW, Quintana RA, Biederman E, Gujral A, Deftos LJ. Parathyroid hormone-releated protein regulates the growth of orthotopic human lung tumors in athymic mice. Cancer. 2001;92(6):1402-10.
  • Jin Y, Liu M, Sa R, Fu H, Cheng L, Chen L. Mouse models of thyroid cancer: bridging pathogenesis and novel therapeutics. Cancer Lett. 2020;469:35-53.
  • Tsubura A, Lai YC, Miki H, Sasaki T, Uehara N, Yuri T, et al. Review: Animal models of N-methyl-N-nitrosourea-induced mammary cancer and retinal degeneration with special emphasis on therapeutic trials. In Vivo. 2011;25(1):11-22.
  • Akbari Bazm M, Naseri L, Khazaei M. Methods of inducing breast cancer in animal models: a systematic review. World Cancer Res J. 2018;5(4):e1182.
  • Zhang HE, Henderson JM, Gorrel MD. Animal models for hepatocellular carcinoma. Biochim Biophys Acta Mol Basis Dis. 2019;1865(5):993-1002.
  • Tatematsu M, Yamamoto M, Shimizu N, Yoshikawa A, Fukami H, Kaminishi M, et al. Induction of glandular stomach cancers in Helicobacter pylori-sensitive Mongolian gerbils treated with N-methyl-N-nitrosourea and N-methyl-N-nitro-N-nitrosoguanidine in drinking water. Jpn J Cancer Res. 1998;89(2):97-104.
  • Bobek P, Galbavy S, Ozdin L. Effect of oyster mushroom (Pleurotus ostreatus) on pathological changes in dimethylhydrazine-induced rat colon cancer. Oncol Rep. 1998;5(3):727-730.
  • Saygı Ş. Toxicity testings and the importance of test results in experimental toxicology. Gülhane Med J. 2003;45(3):291-8. Turkish.
  • İssi M. Removal techniques of blood from laboratory animals. J Bornova Vet Sci. 2008;30(44):43-48. Turkish.

Design of Animal Experiments in Pharmacological Research

Yıl 2024, Cilt: 26 Sayı: S1
https://doi.org/10.18678/dtfd.1489639

Öz

Pharmacology, also known as pharmaceutical science, has made significant progress, especially in the 20th century, and has played a fundamental role in the development of today's modern drugs. Pharmacology uses in vitro, in vivo, and clinical research stages in drug development. Experimental animals are of great importance in in vivo research. The majority of the drugs used today were developed thanks to animal research. Research in which experimental animals will be used should be planned carefully, and a minimum number of animals should be used since the subject is a living being. In addition, one of the most important ethical principles is to avoid procedures that may cause unnecessary torture and pain to animals during experiments. The purpose of pharmacological research is to develop drugs for the treatment or diagnosis of diseases. For this reason, it is aimed at determining the effects of the substance you are researching in the presence of disease. Immediate use of a substance whose effects were previously unknown on humans may lead to various adverse events and even death. After many events in the past, drug development stages have been determined by accepted international rules. According to these rules, the effect of the substance being investigated must be investigated in experimental animals that have been used as disease models before humans. Many disease models have been developed for this purpose. Drugs developed in these disease models created in experimental animals are now successfully used in the treatment of humans.

Kaynakça

  • Jota Baptista CV, Faustino-Rocha AI, Oliveria PA. Animal models in pharmacology: a brief history awarding the Nobel prizes for physiology or medicine. Pharmacology. 2021;106(7-8):356-68.
  • Altun A, Keskin İ. Ethical status and rules for selecting models in animal studies. Sakarya Med J. 2020;10(2):359-64. Turkish.
  • Johnson PD, Besselsen DG. Practical aspects of experimental design in animal research. ILAR J. 2002;43(4):202-6.
  • Yarsan E, editor. Veteriner hekimlikte ilaç uygulama yöntemleri. Ankara: Nobel Kitabevleri; 2019. Turkish.
  • Bora ES, Özlü C. Klinik bilimlerde deney hayvani modelleri. Ankara: Akademisyen Kitabevi. 2020. Turkish.
  • Senio M. Classification criteria of epileptic seizures and syndromes. Epilepsy Res. 2006;70(Suppl 1):S27-33.
  • Marangoz C. Experimental models of epilepsy. J Exp Clin Med. 1997;14(3):147-86. Turkish.
  • McCandless DW, FineSmith RB. Chemically induced model of seizures. In: Boulton AA, Baker GB, Butterworth RF, editors. Animal models of neurological disease, II. Neuromethods, Vol 22. Totowa, NJ: Humana Press; 1992. p.133-51.
  • Miromoto K, Fahnestock M, Racine RJ. Kindling and status epilepticus model of epilepsy: rewiring the brain. Prog Neurobiol. 2004;73(1):1-60.
  • Pitkanen A, Schwartzkroin PA, Moshe SL, editors. Models of seizures and epilepsy. USA: Elsevier Academic Press; 2006.
  • Korkmaz Ü, Kaya M. Experimental models in neurodegenerative diseases. Nucl Med Semin. 2019;5(1):69-77. Turkish.
  • Do Carmo S, Cuello AC. Modeling Alzheimer’s disease in transgenic rats. Mol Neurodegener. 2013;8:37.
  • Elçioğlu HK, Yılmaz G, İlhan B, Karan MA. Experimental animal models for Alzheimer disease. Nobel Med. 2018;14(1):5-13. Turkish.
  • Gubellini P, Kachidian P. Animal models of Parkinson’s disease: An updated overview. Rev Neurol (Paris). 2015;171(11):750-61.
  • Martineau E, Di Polo A, Vande Velde C, Robitaille R. Dynamic neuromuscular remodeling precedes motor-unit loss in a Mouse model of ALS. eLife. 2018;7:e41973.
  • Hao Y, Ge H, Sun M, Gao Y. Selecting an appropriate animal model of depression. Int J Mol Sci. 2019;20(19):4827.
  • Kobeissy FH, editor. Psychiatric disorders: methods and protocols. Totowa, NJ: Humana Press; 2012.
  • Wang Q, Timberlake MA 2nd, Prall K, Dwivedi Y. The recent progress in animal models of depression. Prog Neuropsychopharmacol Biol Psychiatry. 2017;77:99-109.
  • Valvassori SS, Budni J, Varela RB, Quevedo J. Contributions of animal models to the study of mood disorders. Braz J Psychiatry. 2013;35(Suppl 2):S121-31.
  • Padilla E, Barret D, Shumake J, Gonzales-Lima F. Strain, sex and open-field behavior: factors underlying the genetic susceptibility to helplessness. Behav Brain Res. 2009;201(2):257-64.
  • Nam H, Clinton SM, Jackson NL, Kerman IA. Learned helplessness and social avoidance in the Wistar-Kyoto rat. Front Behav Neurosci. 2014;8:109.
  • Powell SB. Models of neurodevelopmental abnormalities in schizophrenia. Curr Top Behav Neurosci. 2010;4:435-81.
  • Tsai G, Coyle JT. Glutamatergic mechanisms in schizophrenia. Annu Rev Pharmacol Toxicol. 2002;42:165-79.
  • Clapcote S, Lipina TV, Millar JK, Mackie S, Christie S, Ogawa F, et al. Behavioral phenotypes of Disc1 missense mutations in mice. Neuron. 2007;54(3):387-402.
  • Basset AS, Chow EW. Schizophrenia and 22q11.2 deletion syndrome. Curr Psyciatry Rep. 2008;10(2):148-57.
  • Uzbay İT. Experimental animal models used in substance addiction studies. Madde bağımlılığı çalışmalarında kullanılan deneysel hayvan modelleri. MİSED. 2009;21-22:49-63. Turkish.
  • Becker JAJ, Kieffer BL, Le Merrer J. Differential behavioral and molecular alterations upon protracted abstinence from cocaine versus morphine, nicotine, THC and alcohol. Addict Biol. 2017;22(5):1205-17.
  • Vanderschuren LJMJ, Minnaard AM, Smeets JAS, Lesscher HMB. Punishment models of addictive behavior. Curr Opin Behav Sci. 2017;13:77-84.
  • Zicha J, Kunes J, Lébl M, Pohlová I, Slaninová J, Jelínek J. Antidiuretic and pressor actions of vasopressin in age-dependent DOCA-salt hypertension. Am J Physiol. 1989;256(1 Pt 2):138-45.
  • Prager-Khoutorsky M, Choe KY, Levi DI, Bourque CW. Role of vasopressin in rat models of salt-dependent hypertension. Curr Hypertens Rep. 2017;19(5):42.
  • Dobrian AD, Davies MJ, Prewitt RL, Lauterio TJ. Development of hypertension in a rat model of diet-induced obesity. Hypertension. 2000;35(4):1009-15.
  • Juskevich JC, Robinson DS, Whitehorn D. Effect of hypothalamic stimulation in spontaneously hypertensive and Wistar-Kyoto rats. Eur J Pharmacol. 1978;51(4):429-39.
  • Bomfim GF, Dos Santos RA, Oliveira MA, Giachini FR, Akamine EH, Tostes RC, et al. Toll-like receptor 4 contributes to blood pressure regulation and vascular contraction in spontaneously hypertensive rats. Clin Sci (Lond). 2012;122(11):535-43.
  • Shikalgar TS, Naikwade NS. Evaluation of cardioprotective activity of fulvic acid against isoproterenol induced oxidative damage in rat myocardium. Int Res J Pharm. 2018;9(1):71-80.
  • Wang J, Bo H, Meng X, Wu Y, Bao Y, Li Y. A simple and fast experimental model of myocardial infarction in the mouse. Texas Heart Inst J. 2006;33(3):290-3.
  • Isorni MA, Casanova A, Piquet J, Bellamy V, Pignon C, Puymirat E, et al. Comparative analysis of methods to induce myocardial infarction in a closed-chest rabbit model. Biomed Res Int. 2015;2015:893051.
  • Zhou S, Wright JL, Liu J, Sin DD, Churg A. Aging does not enhance experimental cigarette smoke-induced COPD in the mouse. PLoS One. 2013;8(8):e71410.
  • Vernooy JH, Dentener MA, van Suylen RJ, Buurman WA, Wouters EF. Long-term intratracheal lipopolysaccharide exposure in mice results in chronic lung inflammation and persistent pathology. Am J Respir Cell Mol Biol. 2002;26(1):152-9.
  • Pera T, Zuidhof A, Valadas J, Smit M, Schoemaker RG, Gosens R, et al. Tiotropium inhibits pulmonary inflammation and remodelling in a guinea pig model of COPD. Eur Respir J. 2011;38(4):789-96.
  • Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology. 1990;98(3):694-702.
  • Neurath MF, Fuss I, Kelsall BL, Stüber E, Strober W. Antibodies to interleukin 12 abrogate established experimental colitis in mice. J Exp Med. 1995;182(5):1281-90.
  • Souza MH, Mota JM, Oliveira RB, Cunha FQ. Gastric damage induced by different doses of indomethacin in rats is variably affected by inhibiting iNOS or leukocyte infiltration. Inflamm Res. 2008;57(1):28-33.
  • Lenzen S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia. 2008;51(2):216-26.
  • Mathews CE. Utility of murine models for the study of spontaneous autoimmune type 1 diabetes. Pediatr Diabetes. 2005;6(3):165-77.
  • Jun HS, Yoon JW. The role of viruses in type 1 diabetes: two distinct cellular and molecular pathogenic mechanisms of virus-induced diabetes in animals. Diabetologia. 2001;44(3):271-85.
  • Allen TJ, Cooper ME, Lan HY. Use of genetic mouse models in the study of diabetic nephropathy. Curr Diab Rep. 2004;4(6):435-40.
  • Pickup JC, Williams G, editors. Textbook of diabetes, 2nd ed. Cambridge, MA: Blackwell Science; 1997.
  • Kim JH, Saxton AM. The TALLYHO mouse as a model of human type 2 diabetes. Methods Mol Biol. 2012;933:75-87.
  • Almosailleakh M, Schwaller J. Murine models of acute myeloid leukaemia. Int J Mol Sci. 2019;20(2):453.
  • Hastings RH, Burton DW, Quintana RA, Biederman E, Gujral A, Deftos LJ. Parathyroid hormone-releated protein regulates the growth of orthotopic human lung tumors in athymic mice. Cancer. 2001;92(6):1402-10.
  • Jin Y, Liu M, Sa R, Fu H, Cheng L, Chen L. Mouse models of thyroid cancer: bridging pathogenesis and novel therapeutics. Cancer Lett. 2020;469:35-53.
  • Tsubura A, Lai YC, Miki H, Sasaki T, Uehara N, Yuri T, et al. Review: Animal models of N-methyl-N-nitrosourea-induced mammary cancer and retinal degeneration with special emphasis on therapeutic trials. In Vivo. 2011;25(1):11-22.
  • Akbari Bazm M, Naseri L, Khazaei M. Methods of inducing breast cancer in animal models: a systematic review. World Cancer Res J. 2018;5(4):e1182.
  • Zhang HE, Henderson JM, Gorrel MD. Animal models for hepatocellular carcinoma. Biochim Biophys Acta Mol Basis Dis. 2019;1865(5):993-1002.
  • Tatematsu M, Yamamoto M, Shimizu N, Yoshikawa A, Fukami H, Kaminishi M, et al. Induction of glandular stomach cancers in Helicobacter pylori-sensitive Mongolian gerbils treated with N-methyl-N-nitrosourea and N-methyl-N-nitro-N-nitrosoguanidine in drinking water. Jpn J Cancer Res. 1998;89(2):97-104.
  • Bobek P, Galbavy S, Ozdin L. Effect of oyster mushroom (Pleurotus ostreatus) on pathological changes in dimethylhydrazine-induced rat colon cancer. Oncol Rep. 1998;5(3):727-730.
  • Saygı Ş. Toxicity testings and the importance of test results in experimental toxicology. Gülhane Med J. 2003;45(3):291-8. Turkish.
  • İssi M. Removal techniques of blood from laboratory animals. J Bornova Vet Sci. 2008;30(44):43-48. Turkish.
Toplam 58 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Klinik Tıp Bilimleri (Diğer)
Bölüm Davetli Derleme
Yazarlar

Nuri Cenk Coşkun

Erken Görünüm Tarihi 24 Mayıs 2024
Yayımlanma Tarihi
Gönderilme Tarihi 29 Şubat 2024
Kabul Tarihi 22 Nisan 2024
Yayımlandığı Sayı Yıl 2024 Cilt: 26 Sayı: S1

Kaynak Göster

APA Coşkun, N. C. (2024). Design of Animal Experiments in Pharmacological Research. Duzce Medical Journal, 26(S1). https://doi.org/10.18678/dtfd.1489639
AMA Coşkun NC. Design of Animal Experiments in Pharmacological Research. Duzce Med J. Mayıs 2024;26(S1). doi:10.18678/dtfd.1489639
Chicago Coşkun, Nuri Cenk. “Design of Animal Experiments in Pharmacological Research”. Duzce Medical Journal 26, sy. S1 (Mayıs 2024). https://doi.org/10.18678/dtfd.1489639.
EndNote Coşkun NC (01 Mayıs 2024) Design of Animal Experiments in Pharmacological Research. Duzce Medical Journal 26 S1
IEEE N. C. Coşkun, “Design of Animal Experiments in Pharmacological Research”, Duzce Med J, c. 26, sy. S1, 2024, doi: 10.18678/dtfd.1489639.
ISNAD Coşkun, Nuri Cenk. “Design of Animal Experiments in Pharmacological Research”. Duzce Medical Journal 26/S1 (Mayıs 2024). https://doi.org/10.18678/dtfd.1489639.
JAMA Coşkun NC. Design of Animal Experiments in Pharmacological Research. Duzce Med J. 2024;26. doi:10.18678/dtfd.1489639.
MLA Coşkun, Nuri Cenk. “Design of Animal Experiments in Pharmacological Research”. Duzce Medical Journal, c. 26, sy. S1, 2024, doi:10.18678/dtfd.1489639.
Vancouver Coşkun NC. Design of Animal Experiments in Pharmacological Research. Duzce Med J. 2024;26(S1).
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