Variability of blood biochemical parameters and establishment of reference intervals in preclinical studies. Part 7: guinea pig

Original article

УДК 001.891.53
DOI: 10.57034/2618723X-2022-03-01

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

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

* E-mail: [email protected]


Keywords: assessment of the clinical state of laboratory animals blood serum biological system laboratory studies mammalian herbivores rodents сavia porcellus

Acknowledgements

The study was performed without external funding.


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 7: guinea pig. Laboratory Animals for Science. 2022; 3. https://doi.org/10.29296/2618723X-2022-03-01

Abstract

The guinea pig is a significant model in preclinical studies because of its optimal body size, wide commercial availability; similarity to humans in anatomical, immunological and biochemical features. The animals in question are widely used for research in allergology and immunology, infectious and cardiovascular diseases, atherosclerosis, and arthritis. In addition, guinea pig metabolism of lipids, cholesterol and glucose is similar to that of humans. Due to the high involvement of these animals in preclinical studies and the possibility of modeling a large number of pathological conditions, an important point is to monitor animal health, assess the condition of internal organs and information on metabolism — the metabolism of lipids, proteins and carbohydrates. The aim of this study was to establish the reference intervals of some biochemical parameters of guinea pig blood serum. These parameters are required in preclinical studies for monitoring animal health, assessing the presence/absence of drift of the studied parameters, comparing the obtained values with human values, and evaluating model pathology. To form the reference intervals we used data obtained from intact healthy animals in December 2021 — April 2022 at «Home оf Pharmacy». All experiments performed were approved by the bioethics commission. The following parameters were determined in the blood serum of the animals on an automatic biochemical analyzer Rendom Access A-25 using appropriate test kits: creatinine, urea, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, high-density lipoproteins, α-amylase, triglycerides, total protein, albumin, glucose, creatine kinase, lactate dehydrogenase and total bilirubin. Based on the total protein content of each animal, the number of globulins was determined and the guinea pig albumin/globulin ratio was calculated. When comparing the obtained and literature data, it was shown that the calculated in the «Home оf Pharmacy» reference values of biochemical parameters of animals in general correlate with those of other research centers and laboratories, which confirms their representativeness. When comparing the obtained values of biochemical blood parameters of guinea pigs with human data, it was shown that some values are similar to each other — creatinine, lactate dehydrogenase, globulins. Alkaline phosphatase, cholesterol, high-density lipoproteins, α-amylase, triglycerides, total bilirubin and glucose differ in the value of the reference range. Urea, alanine aminotransferase and aspartate aminotransferase were higher in animals than in humans. These differences need to be taken into account in further preclinical studies for a more accurate analysis of the results obtained.

Conflict of interest

The authors declare no conflict of interest.

Authors contribution

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, revision of the text.
M.N. Makarova — idea, editing of the text, editing of the text.

References

  1. Акимова М.А., Акимов Д.Ю. Морские свинки в доклинических исследованиях, оптимальные характеристики тест-системы // Лабораторные животные для научных исследований. 2021. № 1. [Akimova M.A., Akimov D.Yu. Morskie svinki v do­klinicheskikh issledovaniyakh, optimal’nye kharakteristiki test-sistemy // Laboratornye zhivotnye dlya nauchnykh issledovaniy. 2021. №. 1. (In Russ.)]. doi: 10.29296/2618723X-2021-01-08.
  2. Taylor D.K., Lee V.K. Guinea pigs as experimental mo­dels // The Laboratory Rabbit, Guinea Pig, Hamster, and Other Rodents. Academic Press, 2012. P. 705–744. doi: 10.1016/B978-0-12-380920-9.00025-0.
  3. Lykkesfeldt J., Tveden-Nyborg P. The pharmacokinetics of vitamin C // Nutrients. 2019. Vol. 11. N. 10. Р. 2412. doi: 10.3390/nu11102412.
  4. Padilla-Carlin D.J., McMurray D.N., Hickey A.J. The gui­nea pig as a model of infectious diseases // Comparative medicine. 2008. Vol. 58. N. 4. Р. 324–340.
  5. Adner M. Canning B.J., Meurs H. et al. Back to the future: re-establishing guinea pig in vivo asthma models // Clinical Science. 2020. Vol. 134. N. 11. P. 1219–1242. doi: 10.1042/CS20200394.
  6. Bouvier N.M., Lowen A.C. Animal models for influenza virus pathogenesis and transmission // Viruses. 2010. Vol. 2. N. 8. P. 1530–1563. doi: 10.3390/v20801530.
  7. Bell T.M., Shaia C.I., Bearss J.J. et al. Temporal progression of lesions in guinea pigs infected with Lassa virus // Veterinary pathology. 2017. Vol. 54. N. 3. P. 549–562. doi: 10.1177/0300985816677153.
  8. Gowen B.B., Juelich T.L., Sefing E.J. et al. Favipiravir (T-705) inhibits Junin virus infection and reduces mortality in a guinea pig model of Argentine hemorrhagic fever // PLoS neglected tropical diseases. 2013. Vol. 7. N. 12. P. e2614. doi: 10.1371/journal.pntd.0002614.
  9. Bente D., Gren J., Strong J., Feldmann H. Disease mo­deling for Ebola and Marburg viruses // Disease models & mechanisms. 2009. Vol. 2. N. 1–2. P. 12–17.
  10. Yoon J.J., Toots M., Lee S. et al. Orally efficacious broad-spectrum ribonucleoside analog inhibitor of influenza and respiratory syncytial viruses // Antimicrobial agents and chemotherapy. 2018. Vol. 62. N. 8. P. e00766–18. doi: 10.1128/AAC.00766-18.
  11. Gonciarz W., Walencka M., Moran A.P. et al. Upregulation of MUC5AC production and deposition of Lewis determinants by Helicobacter pylori facilitate gastric tissue colonization and the maintenance of infection // Journal of Biomedical Science. 2019. Vol. 26. N. 1. P. 1–12. doi: 10.1186/s12929-019-0515-z.
  12. Hunter R.L., Actor J.K., Hwang S.A. et al. Pathogenesis and animal models of post-primary (bronchogenic) tuberculosis, a review // Pathogens. 2018. Vol. 7. N. 1. P. 19. doi: 10.3390/pathogens7010019.
  13. Zhao Y., Qu H., Wang Y. et al. Small rodent models of atherosclerosis // Biomedicine & Pharmacotherapy. 2020. Vol. 129. P. 110426. doi: 10.1016/j.biopha.2020.110426.
  14. Radakovich L.B., Marolf A.J., Culver L.A. et al. Calorie restriction with regular chow, but not a high-fat diet, delays onset of spontaneous osteoarthritis in the Hartley guinea pig model // Arthritis research & therapy. 2019. Vol. 21. N. 1. P. 1–14. doi: 10.1186/s13075-019-1925-8.
  15. Fernandez M.L., Volek J.S. Guinea pigs: a suitable animal model to study lipoprotein metabolism, atherosclerosis and inflammation // Nutrition & metabolism. 2006. Vol. 3. N. 1. P. 1–6. doi: 10.1186/1743-7075-3-17.
  16. Priyadharsini R.P. Animal models to evaluate anti-athe­rosclerotic drugs // Fundamental & Clinical Pharmaco­logy. 2015. Vol. 29. N. 4. P. 329–340.
  17. Witztum J.L., Young S.G., Elam R.L. et al. Cholesty­ramine-induced changes in low density lipoprotein composition and metabolism. I. Studies in the guinea pig // Journal of Lipid Research. 1985. Vol. 26.1. P. 92–103.
  18. Turley S.D., West C.E. Effect of cholesterol and cholestyramine feeding and of fasting on sterol synthesis in the liver, ileum, and lung of the guinea pig // Lipids. 1976. Vol. 11.7. P. 571–577. doi: 10.1007/BF02532904.
  19. Podell B.K., Ackart D.F., Richardson M.A. et al. A model of type 2 diabetes in the guinea pig using sequential diet-induced glucose intolerance and streptozotocin treatment // Disease models & mechanisms. 2017. Vol. 10 (2). P. 151–162. doi: 10.1242/dmm.025593.
  20. Friedrichs K.R., Harr K.E., Freeman K.P. et al. ASVCP reference interval guidelines: determination of de novo reference intervals in veterinary species and other rela­ted topics // Veterinary clinical pathology. 2012. Vol. 41. N. 4. P. 441–453. doi: 10.1111/vcp.12006.
  21. Horn P. S., Pesce A.J. Reference intervals: an update // Clinica Chimica Acta. 2003. Vol. 334 (1–2). Р. 5–23. doi: 10.1016/s0009-8981(03)00133-5.
  22. Dang V., Bao S., Ault A., Murray C. et al. Efficacy and safety of five injectable anesthetic regimens for chronic blood collection from the anterior vena cava of Guinea pigs // Journal of the American Association for Laboratory Animal Science. 2008. Vol. 47 (6). P. 56–60.
  23. Suckow M.A., Stevens K.A., Wilson R.P. (ed.). The laboratory rabbit, guinea pig, hamster, and other rodents. Academic Press, 2012.
  24. Siegel A., Walton R.M. Hematology and Biochemistry of small mammals // Ferrets, Rabbits, and Rodents. 2020. P. 569.
  25. McClure D.E. Clinical pathology and sample collection in the laboratory rodent // Veterinary Clinics of North America: Exotic Animal Practice. 1999. Vol. 2. N. 3. P. 565–590. doi: 10.1016/s1094-9194(17)30111-1.
  26. Baldrey V., Ashpole I. Interpreting blood profiles in non-domestic small mammals. 2012.
  27. Kitagaki M., Yamaguchi M., Nakamura M. et al. Age-related changes in haematology and serum chemistry of Weiser — Maples guineapigs (Cavia porcellus) // Laboratory animals. 2005. Vol. 39 (3). P. 321–330. doi: 10.1258/0023677054307042.
  28. Конвертор единиц измерения используемых в лабораторной и медицинской практике в единицы международной системы СИ. URL.: http://unitslab.com/ru (дата обращения: 01.2022 г.).
  29. https://agmv.ro/wp-content/uploads/2021/06 (дата обращения: 01.2022 г.).
  30. Spittler A.P., Afzali M.F., Bork S.B. et al. Age-and sex-associated differences in hematology and biochemistry parameters of Dunkin Hartley guinea pigs (Cavia porcellus) // Plos one. 2021. Vol. 16. N. 7. P. e0253794. doi: 10.1371/journal.pone.0253794.
  31. https://en.wikivet.net/Guinea_Pig_Biochemistry (дата обращения: 01.2022 г.).
  32. Rabe H. Reference ranges for biochemical parameters in guinea pigs for the Vettest® 8008 blood analyzer // Tierarztliche Praxis. Ausgabe K., Kleintiere/heimtiere. 2011. Vol. 39. N. 3. P. 170–175.
  33. David M. Kurtz, Gregory S. Travlos. The Clinical Chemistry of Laboratory Animals. 3rd Edition. CRC Press, 2017. 1162 p.
  34. Washington I.M., Van Hoosier G. Clinical biochemistry and hematology // The laboratory rabbit, guinea pig, hamster, and other rodents. Academic Press, 2012. P. 57–116.
  35. Hein J., Hartmann K. Labordiagnostische Referenzbereiche bei Meerschweinchen // Tierarztl Prax Ausg K Kleintiere Heimtiere. 2003. Vol. 31. N. 06. P. 383–389. doi: 10.1055/s-0037-1622380.
  36. Rice B.H., Kraft J., Destaillats F. et al. Ruminant-produced trans-fatty acids raise plasma HDL particle concentrations in intact and ovariectomized female Hartley guinea pigs // The Journal of nutrition. 2012. Vol. 1; 142 (9). P. 679–683. doi: 10.3945/jn.112.160077.
  37. Azab A.E., Albasha M.O. Simultaneous administration of aqueous extract of Rosmarinus officinal with nicotine resulted in prevention of induced hepatorenal toxicity in guinea pigs // American Journal of Bioscience and Bioengineering. 2015. Vol. 3. N. 5. P. 80–86.
  38. Лившиц В.М., Сидельникова В.И. Биохимические анализы в клинике: справ.-3-е изд. 2011. [Livshits V.M., Sidel’nikova V.I. Biokhimicheskie analizy v klinike: sprav.-3-e izd. 2011 (In Russ.)].
  39. Ингерлейб М.Б. Медицинские анализы. Самый полный современный справочник [Текст] / М.Б. Ингерлейб. М.: Изд-во АСТ, 2015. 416 с. [Ingerleib M.B. Meditsinskie analizy. Samyi polnyi sovremennyi spravochnik [Tekst] / M.B. Ingerleib. M.: Izd-vo AST, 2015. 416 p. (In Russ.)].
  40. 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’, specifi chnost’) M., 2008. (In Russ.)].

Received: 2022-04-24
Reviewed: 2022-07-07
Accepted for publication: 2022-07-12

You may be interested