The role of animal experiments in the progress of medicine and its current stage has a significant effect. Most of the research in the medical and veterinary fields requires the use of experimental animals. It is a possible fact that the next experimental studies will be realized with the contribution of animal experiments. On the other hand, since humans cannot be included in experimental studies due to ethical reasons, the use of animals is mandatory. There are many models in which experimental animals are used. However, the use of experimental animals also brings some disadvantages. Experimental animals cannot be used randomly for scientific or any other purpose. Even if the experimental protocol was carried out properly, it will invalidate the obtained data if the appropriate experimental model is not chosen for the study. If the wrong experimental model is chosen, it will result in both economic and time loss. For these reasons, how and which model will be applied in internal and surgical branches in experimental studies and subject selection constitute an important problem. Choosing a suitable subject for the study increases the applicability of the studies and ensures that positive results can be obtained. In our article, we planned to compile the experimental models applied in the literature with different aspects including their advantages and disadvantages and to provide the practitioner with ease of choice.
Keywords: Animal use; laboratory animal; experimental animal models; proper animal selection
Tıbbın ilerlemesinde ve günümüzdeki aşamaya gelmesinde, hayvan deneylerinin rolü önemli ölçüde etkilidir. Tıp ve veteriner alanlarındaki araştırmaların birçoğu deney hayvanı kullanımını gerektirmektedir. Bundan sonra yapılacak olan deneysel çalışmaların da hayvan deneylerinin katkılarıyla gerçekleşmesi olası bir gerçektir. Öte yandan, etik nedenlerden dolayı deneysel çalışmalarda insanlara yer verilememesi, hayvanların kullanımını zorunlu kılmaktadır. Deney hayvanlarının kullanıldığı çok sayıda model bulunmaktadır. Fakat deney hayvanlarının kullanımı, birtakım dezavantajları da beraberinde getirmektedir. Bilimsel olarak ya da herhangi başka bir amaç için deney hayvanları rastgele kullanılamazlar. Deney protokolü uygun yürütülmüş olsa da çalışma için uygun deney modeli seçilmez ise elde edilen verileri geçersiz kılacaktır. Yanlış deney modeli seçildiğinde, hem ekonomik hem de zaman kaybı ile sonuçlanacaktır. Bu nedenle deneysel çalışmalarda, dahili ve cerrahi branşlarda hangi modelin nasıl uygulanacağı ve denek seçimi önemli bir sorun oluşturmaktadır. Çalışmaya uygun denek seçimi, çalışmaların uygulanabilirliğini artırmakta ve olumlu sonuçlar alınabilmesini sağlamaktadır. Yazımızda, literatürde uygulanan deney modellerini avantaj ve dezavantajlarını da içeren farklı yönleriyle derlemeyi ve uygulayıcıya seçim kolaylığı sağlamayı planladık.
Anahtar Kelimeler: Hayvan kullanımı; laboratuvar hayvanı; deneysel hayvan modelleri; uygun hayvan seçimi
- Henry J, Baker J, Russell L. Research in laboratory animal and comparative medicine. In: James G, Fox Lynn C, Anderson Franklin M, Loew Fred W, eds. Laboratory Animal Medicine. 2nd ed. Amsterdam, Netherlands: Academic Press; 2002. p.1228-37.
- Hau J. Handbook of Laboratory Animal Science Vol II Animal Models. Hau j, Van Hoosier L. ed. Induced (Experimental) Disease Models. 2nd ed. Boca Raton, US: CRC Press; 2003. p.1-9.[Crossref] [PMC]
- Barbee RW, Turner PV. Incorporating laboratory animal science into responsible biomedical research. ILAR J. 2019;31;60(1):9-16.[Crossref] [PubMed]
- de Aguilar-Nascimento JE. Fundamental steps in experimental design for animal studies. Acta Cir Bras. 2005;20(1):2-8.[Crossref] [PubMed]
- Lipman NS, Perkins SE. Factors that may influence animal research. In: Fox J, Anderson L, Loew F, Quimby F, eds. Laboratory Animal Medicine. 2nd ed. Amsterdam, Netherlands: Academic Press; 2002; p.1143-65.[Crossref]
- Wood MW, Hart LA. Selecting appropriate animal models and strains: making the best use of research, information and outreach. AATEX. 2008;14 Special Issue:303-6.[Link]
- van der Worp HB, Howells DW, Sena ES, Porritt MJ, Rewell S, O'Collins V, et al. Can animal models of disease reliably inform human studies? PLoS Med. 2010;30;7(3):e1000245.[Crossref] [PubMed] [PMC]
- Eddy NB, Leimbach D. Synthetic analgesics. II. Dithienylbutenyl- and dithienylbutylamines. J Pharmacol Exp Ther. 1953;107(3):385-93.[PubMed]
- Koster R, Anderson M, De Beer EJ. Acetic acid for analgesic screening. Federation Proceedings. 1959;18(1):412-7.[Link]
- Raj PP. Ağrı taksonomisi. Erdine S, editör. Ağrı. 1. Baskı. İstanbul: Alemdar Ofset; 2000. p.12-20.
- Jensen TS, Gottrup H, Sindrup SH, Bach FW. The clinical picture of neuropathic pain. Eur J Pharmacol. 2001;19;429(1-3):1-11.[Crossref] [PubMed]
- Wang LX, Wang ZJ. Animal and cellular models of chronic pain. Adv Drug Deliv Rev. 2003;28;55(8):949-65.[Crossref] [PubMed]
- Wuarin-Bierman L, Zahnd GR, Kaufmann F, Burcklen L, Adler J. Hyperalgesia in spontaneous and experimental animal models of diabetic neuropathy. Diabetologia. 1987;30(8):653-8.[PubMed]
- Cavaletti G, Tredici G, Braga M, Tazzari S. Experimental peripheral neuropathy induced in adult rats by repeated intraperitoneal administration of taxol. Exp Neurol. 1995;133(1):64-72.[Crossref] [PubMed]
- Authier N, Fialip J, Eschalier A, Coudoré F. Assessment of allodynia and hyperalgesia after cisplatin administration to rats. Neurosci Lett. 2000;15;291(2):73-6.[Crossref] [PubMed]
- Vural A, Özatik rslan A, Uzunlar K. Deneysel spinal kord travmalarında dopamin ile kombine nimodipin ve nalorfinin etkileri. Ankara Patoloji Bülteni. 1994;11(2):21-5.[Link]
- Döşoğlu M, Kırış T, İzgi N, Ünal ÖF. Omurilik travmalarında ikincil hasar mekanizmaları. Ulus Travma Acil Cerrahi Derg. 1998;4(3):147-57.[Link]
- Montilla MP, Cabo J, Navarro MC, Risco S, Jimenez J, Aneiros J, et al. The protective and curative action of Withania frutescens leaf extract against CCl4-induced hepatotoxicity. Phytotherapy Research. 1990;4(6):212-5.[Crossref]
- Chan-Yeung M. A clinician's approach to determine the diagnosis, prognosis, and therapy of occupational asthma. Med Clin North Am. 1990;74(3):811-22.[Crossref] [PubMed]
- Bousquet J, Jeffery PK, Busse WW, Johnson M, Vignola AM. Asthma. From bronchoconstriction to airways inflammation and remodeling. Am J Respir Crit Care Med. 2000;161(5):1720-45.[Crossref] [PubMed]
- Dietrich WF, Miller J, Steen R, Merchant MA, Damron-Boles D, Husain Z, et al. A comprehensive genetic map of the mouse genome. Nature. 1996;14;380(6570):149-52. Erratum in: Nature. 1996;9;381(6578):172.[Crossref] [PubMed]
- Elias JA, Lee CG, Zheng T, Ma B, Homer RJ, Zhu Z, et al. New insights into the pathogenesis of asthma. J Clin Invest. 2003;111(3):291-7.[Crossref] [PubMed] [PMC]
- Boskabady MH, Rahbardar MG, Jafari Z. The effect of safranal on histamine (H(1)) receptors of guinea pig tracheal chains. Fitoterapia. 2011;82(2):162-7.[Crossref] [PubMed]
- Zosky GR, von Garnier C, Stumbles PA, Holt PG, Sly PD, Turner DJ, et al. The pattern of methacholine responsiveness in mice is dependent on antigen challenge dose. Respir Res. 2004;23;5(1):15.[Crossref] [PubMed] [PMC]
- Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008;83(5):584-94.[Crossref]
- Howard RB, Chu H, Zeligman BE, Marcell T, Bunn PA, McLemore TL, et al. Irradiated nude rat model for orthotopic human lung cancers. Cancer Res. 1991;15;51(12):3274-80.[PubMed]
- Hastings RH, Burton DW, Quintana RA, Biederman E, Gujral A, Deftos LJ, et al. Parathyroid hormone-related protein regulates the growth of orthotopic human lung tumors in athymic mice. Cancer. 2001;15;92(6):1402-10.[Crossref] [PubMed]
- Kellar A, Egan C, Morris D. Preclinical murine models for lung cancer: clinical trial applications. Biomed Res Int. 2015;2015:621324.[Crossref] [PubMed] [PMC]
- Memon AA, Jakobsen S, Dagnaes-Hansen F, Sorensen BS, Keiding S, Nexo E, et al. Positron emission tomography (PET) imaging with [11C]-labeled erlotinib: a micro-PET study on mice with lung tumor xenografts. Cancer Res. 2009;1;69(3):873-8.[Crossref] [PubMed]
- Steiner P, Joynes C, Bassi R, Wang S, Tonra JR, Hadari YR, et al. Tumor growth inhibition with cetuximab and chemotherapy in non-small cell lung cancer xenografts expressing wild-type and mutated epidermal growth factor receptor. Clin Cancer Res. 2007;1;13(5):1540-51.[Crossref] [PubMed]
- Sakuma Y, Matsukuma S, Nakamura Y, Yoshihara M, Koizume S, Sekiguchi H, et al. Enhanced autophagy is required for survival in EGFR-independent EGFR-mutant lung adenocarcinoma cells. Lab Invest. 2013;93(10):1137-46.[Crossref] [PubMed]
- Akhtar S, Meeran SM, Katiyar N, Katiyar SK. Grape seed proanthocyanidins inhibit the growth of human non-small cell lung cancer xenografts by targeting insulin-like growth factor binding protein-3, tumor cell proliferation, and angiogenic factors. Clin Cancer Res. 2009;1;15(3):821-31. Erratum in: Clin Cancer Res. 2018;1;24(23):6101.[Crossref] [PubMed]
- Chen MF, Chen WC, Wu CT, Lin PY, Shau H, Liao SK, et al. p53 status is a major determinant of effects of decreasing peroxiredoxin I expression on tumor growth and response of lung cancer cells to treatment. Int J Radiat Oncol Biol Phys. 2006;1;66(5):1461-72.[Crossref] [PubMed]
- Wang H, Li M, Rinehart JJ, Zhang R. Pretreatment with dexamethasone increases antitumor activity of carboplatin and gemcitabine in mice bearing human cancer xenografts: in vivo activity, pharmacokinetics, and clinical implications for cancer chemotherapy. Clin Cancer Res. 2004;1;10(5):1633-44.[Crossref] [PubMed]
- McLemore TL, Liu MC, Blacker PC, Gregg M, Alley MC, Abbott BJ, et al. Novel intrapulmonary model for orthotopic propagation of human lung cancers in athymic nude mice. Cancer Res. 1987;1;47(19):5132-40.[PubMed]
- Carter CA, Chen C, Brink C, Vincent P, Maxuitenko YY, Gilbert KS, et al. Sorafenib is efficacious and tolerated in combination with cytotoxic or cytostatic agents in preclinical models of human non-small cell lung carcinoma. Cancer Chemother Pharmacol. 2007;59(2):183-95.[Crossref] [PubMed]
- Feng Z, Zhao G, Yu L, Gough D, Howell SB. Preclinical efficacy studies of a novel nanoparticle-based formulation of paclitaxel that out-performs Abraxane. Cancer Chemother Pharmacol. 2010;65(5):923-30.[Crossref] [PubMed] [PMC]
- Yamori T, Sato S, Chikazawa H, Kadota T. Anti-tumor efficacy of paclitaxel against human lung cancer xenografts. Jpn J Cancer Res. 1997;88(12):1205-10.[Crossref] [PubMed] [PMC]
- Sakai Y, Sasahira T, Ohmori H, Yoshida K, Kuniyasu H. Conjugated linoleic acid reduced metastasized LL2 tumors in mouse peritoneum. Virchows Arch. 2006;449(3):341-7.[Crossref] [PubMed]
- Akbay E, Onur MA, Gürpınar ÖA. [Myocardial infarction models]. Turkiye Klinikleri J Cardiovasc Surg-Special Topics. 2013;5(3):49-57.[Link]
- Karasu-Minareci E, Öğütman Ç. [Experimental animal models for cardiovascular diseases]. Turkiye Klinikleri J Cardiovasc Sci. 2011;23(1):65-74.[Link]
- Bopda OS, Longo F, Bella TN, Edzah PM, Taïwe GS, Bilanda DC, et al. Antihypertensive activities of the aqueous extract of Kalanchoe pinnata (Crassulaceae) in high salt-loaded rats. J Ethnopharmacol. 2014;28;153(2):400-7.[Crossref] [PubMed]
- Qui-ones M,Guerrero L, Suarez M, Pons Z, Aleixandre A, Arola L, et al. Low-molecular procyanidin rich grape seed extract exerts antihypertensive effect in males spontaneously hypertensive rats. Food Research International. 2013;51(2):587-95.[Crossref]
- Sun ZJ, Zhang ZE. Historic perspectives and recent advances in major animal models of hypertension. Acta Pharmacol Sin. 2005;26(3):295-301.[Crossref] [PubMed]
- Selye H. Production of nephrosclerosis by overdosage with desoxycorticosterone acetate. Can Med Assoc J. 1942;47(6):515-9.[PubMed] [PMC]
- Terris JM, Berecek KH, Cohen EL, Stanley JC, Whitehouse WM Jr, Bohr DF, et al. Deoxycorticosterone hypertension in the pig. Clin Sci Mol Med Suppl. 1976;3:303s-5s.[Crossref] [PubMed]
- Bois P, Selye H. The hormonal production of nephrosclerosis and periarteritis nodosa in the primate. Br Med J. 1957;26;1(5012):183-6.[Crossref] [PubMed] [PMC]
- Crofton JT, Share L. Gonadal hormones modulate deoxycorticosterone-salt hypertension in male and female rats. Hypertension. 1997;29(1 Pt 2):494-9.[Crossref] [PubMed]
- Dahl LK, Heine M, Tassinari L. Effects of chronic excess salt ingestion. Further demonstration that genetic factors influence the development of hypertension: evidence from experimental hypertension due to cortisone and to adrenal regeneration. J Exp Med. 1965;1;122(3):533-45.[Crossref] [PubMed] [PMC]
- Knowlton AI, Loeb EN, Stoerk HC, Whıte JP, Heffernan JF. Induction of arterial hypertension in normal and adrenalectomized rats given cortisone acetate. J Exp Med. 1952;96(3):187-205.[Crossref] [PubMed] [PMC]
- Ergül Erkeç Ö. Tıbbi çalışmalarda hayvan modelleri. Int J Hum Sci Uluslararası İnsan Bilim Derg. 2014;50-63.[Crossref]
- Baskurt OK, Marshall-Gradisnik S, Pyne M, Simmonds M, Brenu E, Christy R, et al. Assessment of the hemorheological profile of koala and echidna. Zoology (Jena). 2010;113(2):110-7.[Crossref] [PubMed] [PMC]
- Bailey SR, Habershon-Butcher JL, Ransom KJ, Elliott J, Menzies-Gow NJ. Hypertension and insulin resistance in a mixed-breed population of ponies predisposed to laminitis. Am J Vet Res. 2008;69(1):122-9.[Crossref] [PubMed]
- Reaven GM. Role of insulin resistance in human disease. Diabetes. 1988;37(12):1595-1607.[Crossref] [PubMed]
- Emanuela F, Grazia M, Marco de R, Maria Paola L, Giorgio F, Marco B, et al. Inflammation as a link between obesity and metabolic syndrome. J Nutr Metab. 2012;2012:476380.[Crossref] [PubMed] [PMC]
- Kaplan NM. The deadly quartet. Upper-body obesity, glucose intolerance, hypertriglyceridemia, and hypertension. Arch Intern Med. 1989;149(7):1514-20.[Crossref] [PubMed]
- Kim SH, Reaven GM. The metabolic syndrome: one step forward, two steps back. Diab Vasc Dis Res. 2004;1(2):68-75.[Crossref] [PubMed]
- Caltabilota TJ, Earl LR, Thompson DL Jr, Clavier SE, Mitcham PB. Hyperleptinemia in mares and geldings: assessment of insulin sensitivity from glucose responses to insulin injection. J Anim Sci. 2010;88(9):2940-9.[Crossref] [PubMed]
- Panchal SK, Brown L. Rodent models for metabolic syndrome research. J Biomed Biotechnol. 2011;2011:351982.[Crossref] [PubMed] [PMC]
- Polotsky VY. Mouse model of the metabolic syndrome: the quest continues. J Appl Physiol (1985). 2007;102(6):2088-9.[Crossref] [PubMed]
- Sharma K, McCue P, Dunn SR. Diabetic kidney disease in the db/db mouse. Am J Physiol Renal Physiol. 2003;284(6):F1138-44.[Crossref] [PubMed]
- Shafrir E, Ziv E. A useful list of spontaneously arising animal models of obesity and diabetes. Am J Physiol Endocrinol Metab. 2009;296(6):E1450-2.[Crossref] [PubMed]
- Silva APS, Guimarâes DED, Mizurini DM, Maia IC, Ortiz-Costa S, Sardinha FL, et al. Dietary fatty acids early in life affect lipid metabolism and adiposity in young rats. Lipids. 2006;41(6):535-41.[Crossref] [PubMed]
- Akagiri S, Naito Y, Yoshikawa T. Diyet and metabolic syndrome. J Biol Macromol. 2009;9(2):39-48.[Link]
- Basciano H, Federico L, Adeli K. Fructose, insulin resistance, and metabolic dyslipidemia. Nutr Metab (Lond). 2005;21;2(1):5.[Crossref] [PubMed] [PMC]
- Santos MP, França SA, Santos JT, Buzelle SL, Bertolini GL, Garófalo MA, et al. A low-protein, high-carbohydrate diet increases fatty acid uptake and reduces norepinephrine-induced lipolysis in rat retroperitoneal white adipose tissue. Lipids. 2012;47(3):279-89.[Crossref] [PubMed]
- Desrois M, Sidell RJ, Gauguier D, King LM, Radda GK, Clarke K, et al. Initial steps of insulin signaling and glucose transport are defective in the type 2 diabetic rat heart. Cardiovasc Res. 2004;1;61(2):288-96.[Crossref] [PubMed]
- Mizoguchi A, Mizoguchi E. Animal models of IBD: linkage to human disease. Curr Opin Pharmacol. 2010;10(5):578-87.[Crossref] [PubMed] [PMC]
- DeVoss J, Diehl L. Murine models of inflammatory bowel disease (IBD): challenges of modeling human disease. Toxicol Pathol. 2014;42(1):99-110.[Crossref] [PubMed]
- Jones-Hall YL, Grisham MB. Immunopathological characterization of selected mouse models of inflammatory bowel disease: Comparison to human disease. Pathophysiology. 2014;21(4):267-88.[Crossref] [PubMed]
- te Velde AA, de Kort F, Sterrenburg E, Pronk I, ten Kate FJ, Hommes DW, et al. Comparative analysis of colonic gene expression of three experimental colitis models mimicking inflammatory bowel disease. Inflamm Bowel Dis. 2007;13(3):325-30.[Crossref] [PubMed]
- Erben U, Loddenkemper C, Doerfel K, Spieckermann S, Haller D, Heimesaat MM, et al. A guide to histomorphological evaluation of intestinal inflammation in mouse models. Int J Clin Exp Pathol. 2014;15;7(8):4557-76.[PubMed] [PMC]
- Gibson-Corley KN, Olivier AK, Meyerholz DK. Principles for valid histopathologic scoring in research. Vet Pathol. 2013;50(6):1007-15.[Crossref] [PubMed] [PMC]
- Ngo ST, Steyn FJ, McCombe PA. Gender differences in autoimmune disease. Front Neuroendocrinol. 2014;35(3):347-69.[Crossref] [PubMed]
- Bouma G, Kaushiva A, Strober W. Experimental murine colitis is regulated by two genetic loci, including one on chromosome 11 that regulates IL-12 responses. Gastroenterology. 2002;123(2):554-65.[Crossref] [PubMed]
- Alex P, Zachos NC, Nguyen T, Gonzales L, Chen TE, Conklin LS, et al. Distinct cytokine patterns identified from multiplex profiles of murine DSS and TNBS-induced colitis. Inflamm Bowel Dis. 2009;15(3):341-52.[Crossref] [PubMed] [PMC]
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