Variability of blood biochemical parameters and establishment of reference intervals in preclinical studies. Part 5: ferrets

DOI: 10.29296/2618723X-2021-04-04

M.V. Miroshnikov, Candidate of Medical Sciences, Head of the Laboratory of Biochemistry and Hematology,
ORCHID 0000-0002-9828-3242;
K.T. Sultanova, Candidate of Medical Sciences, ORCHID 0000-0002-9846-8335;
M.A. Kovaleva, Candidate of Biological Sciences, Head of the scientific and methodological group,
ORCHID 0000-0002-0740-9357;
M.N. Makarova, MD, Director, ORCHID 0000-0003-3176-6386

Research and manufacturing company «Home оf Pharmacy»,
188663, Russia, Leningrad oblast, Vsevolozhskiy district, Kuzmolovskiy t.s., Zavodskaya st. 3-245

Е-mail: [email protected]

Keywords: assessment of the state of laboratory animals blood serum biological system laboratory research

For citation:

Miroshnikov M.V., Sultanova K.T., Kovaleva M.A., Makarova M.N. Variability of blood biochemical parameters and establishment of reference intervals in preclinical studies. Part 5: ferrets. Laboratory Animals for Science. 2021; 4.


Despite the relatively small number in preclinical studies, ferrets occupy a certain niche and have several unique features. Ferrets are used as models in the study of gastrointestinal and tumor diseases, cardiovascular pathology, as well as in research on the development of the nervous and visual systems. There is a significant similarity in the physiology and morphology of the lungs of ferrets and humans, and therefore this animal species is used as a model for studying cystic fibrosis, influenza and COVID-19. The purpose of this work is to summarize the results of biochemical blood parameters obtained in earlier studies on ferrets based on the NGO "House оf Pharmacy" in the period from January to June 2021 to establish reference values of the most frequently determined biochemical parameters.  A retrospective analysis of the data of 11 indicators was carried out.   A sample consisting of 112 females (56 males and 56 females) was analyzed, the body weight of females was 1200–1700 g, the body weight of males was 1500–1900 g. The animals were obtained from LLC "Novye Meha". During the adaptation period and subsequent experiments, the animals were kept in the same standard vivarium conditions: air temperature 22–26 ° C, relative humidity 40-75%, 12-hour daylight. Ferrets were fed in accordance with Directive 2010/63/EU of the European Parliament and of the Council of the European Union of September 22, 2010 on the protection of animals used for scientific purposes. The study was carried out in compliance with the principles of the European Convention for the Protection of Vertebrates Used for Experiments and Other Scientific Purposes (Strasbourg, 1986) and in accordance with the rules of good laboratory practice. Determination of biochemical parameters for all animals was carried out under equal conditions using generally accepted analytical methods. The following parameters were determined in the blood serum of animals: creatinine, urea, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, cholesterol, triglycerides, total protein, albumin, glucose and total bilirubin. When comparing the obtained and the literature data, it was shown that the reference values of biochemical parameters of ferrets calculated in JSC NPO Dom Pharmacy generally correlate with those of other scientific centers and laboratories, which confirms the reliability of the data obtained. The reference intervals of biochemical examination of ferret blood presented in the article confirm the relevance of periodic revision of indicators and indicate the importance of the results obtained for an adequate interpretation of the data obtained in the laboratory of biochemistry. A comparative analysis of the interindividual variability of biochemical parameters of ferret and human blood demonstrates the presence of species differences that must be taken into account when considering the results of preclinical studies.

Full text avaliable in Russain only 


The study was performed without external funding.

Authors’ contributions

M.V. Miroshnikov – analysis of scientific literature and guidelines, writing, editing and revision of the text, carrying responsibility for all aspects of the study related to the reliability of the data
K.T. Sultanova – writing and editing of the text, summarising the study results, preparation of the tables
M.A. Kovaleva – аnalysis of scientific literature and guidelines, editing and revision of the text.
M.N. Makarova – idea, planning of the study design, editing of the text



Conflict of interest

The authors declare no conflicts of interest.


  1. Bähr A., Wolf E. Domestic animal models for biomedical research // Reproduction in domestic animals. – 2012. – Vol.47. – Р. 59-71.
  2. Park S.E., Schaer T.P. Preclinical animal models // Academic Entrepreneurship for Medical and Health Scientists. – 2019. – Vol.1. – №. 3. – Р. 20.
  3. Varga O.E., Hansen A.K., Sandøe P., Olsson I.A.S. Validating animal models for preclinical research: a scientific and ethical discussion // Alternatives to Laboratory Animals. – 2010. – Vol.38. – №. 3. – Р. 245-248.
  4. Ball R.S. Issues to consider for preparing ferrets as research subjects in the laboratory // ILAR journal. – 2006. – Vol. 47. – №. 4. – P. 348-357.
  5. Gad S. C. Pigs and ferrets as models in toxicology and biological safety assessment // International journal of toxicology. – 2000. – Vol. 19. – №. 3. – P. 149-168.
  6. Siegel A., Walton R. M. Hematology and Biochemistry of small mammals //Ferrets, Rabbits, and Rodents. – 2020. – P. 569.
  7. Fox J.G., Adrian L. Gastric Helicobacter infection in animals: natural and experimental infections // Helicobacter pylori Biology and Clinical Practice. – CRC Press, 2018. – P. 407-430.
  8. Whary M.T., Fox J.G. Natural and experimental Helicobacter infections // Comparative medicine. – 2004. – Vol. 54. – №. 2. – P. 128-158.
  9. Burkitt M.D., Duckworth C.A., Williams J.M. Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models // Disease models & mechanisms. – 2017. – Vol. 10. – №. 2. – P. 89-104.
  10. Fox J. G., Marini R. P. (ed.). Biology and Diseases of the Ferret. – John Wiley & Sons, 2014.
  11. Raila J., Gomez C., Schweigert F. J. The ferret as a model for vitamin A metabolism in carnivores // The Journal of nutrition. – 2002. – Vol. 132. – №. 6. – P. 1787S-1789S.
  12. Wang J., Ma Y., Sachs F. GsMTx4-D is a cardioprotectant against myocardial infarction during ischemia and reperfusion // Journal of molecular and cellular cardiology. – 2016. – Vol. 98. – P. 83-94.
  13. Van Riel D., Verdijk R., Kuiken T. The olfactory nerve: a shortcut for influenza and other viral diseases into the central nervous system //The Journal of pathology. – 2015. – Vol. 235 (№2). – P. 277-287.
  14. Barica, R., Engelhardtb, J., Gibbsc, R. Genomic and EST Sequencing of the Ferret (Mustela putorius furo). – 2013.
  15. Morrisey J. K. and Rebecca L. Malakoff, DVM, Diplomate ACVIM (Cardiology, Internal Medicine) //Ferrets, Rabbits and Rodents-E-Book: Clinical Medicine and Surgery. – 2020. – P. 55.
  16. Li Z., Jiang Q., Rezaei Sabet M. Conditions for in vitro maturation and artificial activation of ferret oocytes //Biology of reproduction. – 2002. – Vol. 66. – №. 5. – P. 1380-1386.
  17. Belser J.A., Pulit-Penaloza J.A., Maines T.R. Ferreting out influenza virus pathogenicity and transmissibility: Past and future risk assessments in the ferret model // Cold Spring Harbor perspectives in medicine. – 2020. – Vol. 10. – №. 7. – P. a038323.
  18. Nachbagauer R., Liu W.C., Choi A.A universal influenza virus vaccine candidate confers protection against pandemic H1N1 infection in preclinical ferret studies // npj Vaccines. – 2017. – Vol. 2. – №. 1. – P. 1-13.
  19. Крышень, К. Л., Кательникова, А. Е., Макарова, М. Н., Макаров, В. Г. Особенности экспериментальной работы с хорьками //Лабораторные животные для научных исследований. – 2019. – №. 2. [Kryshen K.L., Katelnikova А.Е., Makarova M.N., Makarov V.G. Peculiarities of Biomedical Experiments Involving Ferrets // Laboratory Animals for Science. – 2019. – №. 2. (in Russ.)].
  20. Maher J.A., DeStefano J. The ferret: an animal model to study influenza virus // Lab animal. – 2004. – Vol. 33. – №. 9. – P. 50-53.
  21. Cleary S.J., Pitchford S.C., Amison R. T. Animal models of mechanisms of SARS-CoV-2 infection and COVID-19 pathology // British journal of pharmacology. – 2020. – Vol. 177. – №. 21. – P. 4851-4865.
  22. Mardani, R., Vasmehjani, A. A., Zali, F. SARS-CoV-2 host diversity: An update of natural infections and experimental evidence //Journal of Microbiology, Immunology and Infection. – 2021. – Vol. 54. – №. 2. – Р. 175-181.
  23. Peng, X., Alföldi, J., Gori, K. The draft genome sequence of the ferret (Mustela putorius furo) facilitates study of human respiratory disease //Nature biotechnology. – 2014. – Vol. 32. – №. 12. – P. 1250-1255.
  24. Kannan K.S., Manoj K., Arumugam S. Labeling methods for identifying outliers // International Journal of Statistics and Systems. – 2015. – Т. 10. – №. 2. – С. 231-238.
  25. Giner J., Villanueva-Saz S., Tobajas A. P. SARS-CoV-2 seroprevalence in household domestic ferrets (Mustela putorius furo) // Animals. – 2021. – Vol. 11. – №. 3. – P. 667.
  26. Huynh M., Laloi F. Diagnosis of liver disease in domestic ferrets (Mustela putorius) // Veterinary Clinics: Exotic Animal Practice. – 2013. – Vol. 16. – №. 1. – P. 121-144.
  27. Hoffmann W.E., Solter P.F. Diagnostic enzymology of domestic animals //Clinical biochemistry of domestic animals. – 2008. – Vol. 6. – P. 351-378.
  28. Hein J., Spreyer F., Sauter-Louis C. Reference ranges for laboratory parameters in ferrets // Veterinary Record. – 2012. – Vol. 171. – №. 9. – P. 218-218.
  29. Greenacre C.B. Avian and Exotic Companion Animals //Nephrology and Urology of Small Animals. – 2011. – P. 855-876.
  30. Войтенко Н.Г., Макарова М.Н. Вариабельность биохимических показателей крови и установление референсных интервалов в доклинических исследованиях. Сообщение 3: карликовые свиньи // Лабораторные животные для научных исследований. – 2020. – №. 3. [Voitenko N.G., Makarova M.N. Variability of blood biochemical parameters and establishment of reference intervals in preclinical studies.Part 3: mini pigs. Laboratory Animals for Science. – 2020. – № 3. – P. 7–15(in Russ.)].
  31. Войтенко Н.Г., Макарова М.Н., Зуева А.А. Вариабельность биохимических показателей крови и установление референсных интервалов в доклинических исследованиях. Сообщение 1: крысы // Лабораторные животные для научных исследований. – 2020. – №. 1. – С. 47-53. [Voitenko N.G., Makarova M.N., Zueva A.A. Variability of blood biochemical parameters and establishing of reference ranges in nonclinical studies. Part 1: rats // Laboratory Animals for Science. – 2020. – № 1. – P. 42-53. (in Russ.)].
  32. Ellis C. Ferrets // Saunders Manual of Small Animal Practice. – 2006. – P. 1816.
  33. Hall B.A., Ketz-Riley C.J. Cholestasis and cholelithiasis in a domestic ferret (Mustela putorius furo) // Journal of Veterinary Diagnostic Investigation. – 2011. – Vol. 23. – №. 4. – P. 836-839.
  34. Mayer J. Interpreting the chemistry profile in ferrets // Proc North American Veterinary Conference. Orlando, FL, USA. – 2008.
  35. Лившиц В. М., Сидельникова В. И. Биохимические анализы в клинике: справ.-3-е изд. – 2011.
  36. Whalan J. E. A toxicologist's guide to clinical pathology in animals //Hematology, clinical chemistry, urinalysis. Switzerland: Springer International Publishing. – 2015.
  37. Mardani R. et al. Laboratory parameters in detection of COVID-19 patients with positive RT-PCR; a diagnostic accuracy study //Archives of academic emergency medicine. – 2020. – Р. 8. – №. 1.
  38. Конвертор единиц измерения используемых в лабораторной и медицинской практике в единицы международной системы СИ. – URL.: (дата обращения: 08.2021 г.).
  39. Matchett C. A., Marr R., Berard F. M. The laboratory ferret. – CRC Press, 2019.
  40. Fudge A. M. Laboratory medicine: avian and exotic pets. – 2000.
  41. Greenacre C. B. Ferrets //Exotic Animal Laboratory Diagnosis. – 2020. – P. 17-44.
  42. Lee E.J., Moore W.E., Fryer H.C. Haematological and serum chemistry profiles of ferrets (Mustela putorius furo) //Laboratory Animals. – 1982. – Vol. 16. – №. 2. – P. 133-137.
  43. Kurtz D. M., Travlos G. S. (ed.). The clinical chemistry of laboratory animals. – CRC Press, 2017.
  44. Deng, X., Liu, B., Li, J. Blood biochemical characteristics of patients with coronavirus disease 2019 (COVID-19): a systemic review and meta-analysis //Clinical Chemistry and Laboratory Medicine (CCLM). – 2020. – Vol. 58. – №. 8. – P. 1172-1181.
  45. ГОСТ Р 53022.2–2008 Технологии лабораторные клинические. Требования к качеству клинических лабораторных исследований. Часть 2. Оценка аналитической надежности методов исследования (точность, чувствительность, специфичность) М., 2008. [GOST R 53022.2–2008 Tekhnologii laboratornye klinicheskie. Trebovaniya k kachestvu klinicheskih laboratornyh issledovanij. CHast' 2. Ocenka analiticheskoj nadezhnosti metodov issledovaniya (tochnost', chuvstvitel'nost', specifichnost') M., 2008. (In Russ.)]

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