Features of blood parameters and adaptational status of Balb/c and C57Bl/6 mice lines in the absence of special influences

Purpose of the study. A comparative analysis of blood parameters and some characteristics of the adaptation status of intact Balb/c and C57Bl/6 mice of both sexes.

Materials and methods. We investigated intact mice of both sexes belonging to the C57Bl/6 (n = 18) and Balb/c (n = 20) lines. The age characteristics of these animals corresponded to the first half of the reproductive period. We studied the parameters of the complete and biochemical blood tests, the weight characteristics of the thymus, spleen and adrenal glands. The character and tension of general nonspecific adaptational reactions of the body (AR) were assessed as well. In statistical analysis we used the coefficient of variation (CV), Student's t-test, Mann-Whitney test.

Results. In mice of both studied lines, the dominance of females over males was noted in terms of the weight characteristics of the thymus and spleen, the development of the most favorable antistress AR, and the number of indicators with low variability. At the same time, in C57Bl/6 mice, animals of different sexes had a similar nature of AR (AR of elevated activation),but differed in signs of tension, this might indicate the difference in the range of levels of reactivity, appropriate to AR in males and females C57Bl/6. Unlike C57Bl/6, mice Balb/c mice of different sexes were distinguished with the predominant antistress AR. Differences between C57Bl/6 mice and Balb/c mice in terms of amylase and ALT activity indicated a shift towards carbohydrate metabolism in Balb/c mice and a shift towards protein metabolism in C57Bl/6 mice. Animals of the С57Bl/6 line had an advantage over Balb/c mice (especially pronounced in females) in some indicators of the adaptation status.

Conclusion. The results of the study indicated possible difference in the ratio of carbohydrate and protein metabolism in the animals of the studied lines and testified a more favorable state of the regulatory systems in C57Bl/6 mice compared to animals of the Balb/c line. The revealed regulatory and metabolic interlinear differences can determine the features in the reaction of the body of animals belonging to different lines to the malignant process and efficiency of antitumor therapy.

1. Karkischenko VN, Schmidt EF, Braitseva EV. The researchers prefer BALB/c mice. Journal Biomed. 2007;(1):57–70. (In Russ.). EDN: NTSTLJ

2. Zhukova GV, Schikhlyarova AI, Barteneva TA, Shevchenko AN, Zakharyuta FM. Effect of Thymalin on the Tumor and Thymus under Conditions of Activation Therapy In Vivo. Bull Exp Biol Med. 2018 May 1;165(1):80–83. https://doi.org/10.1007/s10517-018-4104-z, EDN: XXKARF

3. Kit OI, Frantsiyants EM, Kozlova LS, Kaplieva IV, Bandovkina VA, Pogorelova YuA, et all. Urokinase and its receptor in cutaneous melanoma reproduced in chronic neurogenic pain in mice of both genders in comparison. Problems in Oncology. 2020;66(4):445–450. (In Russ.). https://doi.org/10.37469/0507-3758-2020-66-4-445-450, EDN: HMDEUV

4. Makarova OV, Postovalova EA, Gao Yu, Dobrynina MT. Sex differences of subpopulation composition of lymphocytes in the peripheral blood in experimental acute and chronic ulcerative colitis. Medical Immunology (Russia). 2020;22(1):157–164. (In Russ.). https://doi.org/10.15789/1563-0625-SDO-1661

5. Hensel JA, Khattar V, Ashton R, Ponnazhagan S. Characterization of immune cell subtypes in three commonly used mouse strains reveals gender and strain-specific variations. Lab Invest. 2019 Jan;99(1):93–106. https://doi.org/10.1038/s41374-018-0137-1

6. Pinchuk LM, Filipov NM. Differential effects of age on circulating and splenic leukocyte populations in C57BL/6 and BALB/ c male mice. Immun Ageing. 2008 Feb 11;5:1. https://doi.org/10.1186/1742-4933-5-1

7. Ahsani DN, Fidianingsih I. Age-related changes of malondialdehyde, body weight and organ weight in male mice. Universa Medicina. 2018 Jun 25;37(2):115–126. https://doi.org/10.18051/UnivMed.2018.v37.115-126

8. Ermakova AV, Kudyasheva AG. Variability of hematological parameters in different species of laboratory mice. Proceedings of the Komi Science Centre of the Ural Division of the Russian Academy of Sciences. 2021;5(51):13–19. (In Russ.). https://doi.org/10.19110/1994-5655-2021-5-13-19, EDN: OTYKKI

9. Abrashova TV, Gushchin YaA, Kovaleva MA, Rybakova AV, Selezneva AI, Sokolova AP, et al. Guide. Physiological, biochemical and biometric indicators of the norm of experimental animals. St. Petersburg: Publishing house "LEMA", 2013, 116 p. (In Russ.). EDN: PTSRUO

10. Zapadnyuk IP, Zapadnyuk VI, Zakharia EA, Zapadnyuk BV. Laboratory animals. Breeding, maintenance, use in the experiment. Kiev: Vishcha shkola, 3rd ed., 1983, 383 p. (In Russ.).

11. Kashkin V. Differences in the behavior of two line C57BL/6 and BALB/C mice in the "open field" test in the background of pregabalin. Laboratory Animals for Science. 2020;4. (In Russ.). https://doi.org/10.29296/2618723X-2020-04-09

12. Wirth-Dzięciołowska E, Karaszewska J, Sadowski T, Pyśniak K, Gajewska M. Selected blood serum biochemical indicators in twelve inbred strains of laboratory mice. Animal Science Papers and Reports. 2009;27(2):159–167. Available at: https://www.yumpu.com/en/document/read/22548022/selected-blood-serum-biochemical-indicators-in-twelve-inbred-, Accessed: 27.03.2023.

13. Semenov KK, Karkischenko NN, Kazakova LK, Beskova TB, Lushnikova ZS, Egorova IYu, et al. Interlinear distinctions in sensitivity to a sharp hypobaric hypoxia at inbred mice of collection fund. Journal Biomed. 2013;1(1):78–82. (In Russ.). EDN: RTGJEJ

14. Flint MS, Tinkle SS. C57BL/6 mice are resistant to acute restraint modulation of cutaneous hypersensitivity. Toxicol Sci. 2001 Aug;62(2):250–256, https://doi.org/10.1093/toxsci/62.2.250

15. Pialek J, Vyskocilová M, Bímová B, Havelková D, Piálková J, Dufková P, et al. Development of unique house mouse resources suitable for evolutionary studies of speciation. J Hered. 2008;99(1):34–44. https://doi.org/0.1093/jhered/esm083

16. Amstislavskaya ET, Novikov SN. Activation response of testicular endocrine system induced by the exposure to a female in C57BL/6J mice. Laboratory Animals for Science. 2018;3. (In Russ.). https://doi.org/10.29296/2618723X-2018-03-01

17. Selye H. Thymus and adrenals in the response of the organisms to injuries and intoxication. British Journal of Experimental Pathology. 1936;17:234–224.

18. Garkavi LH, Kvakina EB, Kuz'menko TS, SHihlyarova AI. Anti-stress reactions and activation therapy. Ekaterinburg: Filantrop, 2002, 196 p. (In Russ.). EDN: XMYPUT

19. Astashkin EI, Achkasov EE, Afonin KV, Berzin IA, Beskova TB, Bolotskikh LA, et al. The guide to laboratory animals and alternative models in biomedical researches. Moscow: Profil – 2C, 2010, 358 p. (In Russ.). EDN: UAOCKN

20. Zhukova GV, Frantsyants EM, Shikhlyarova AI, Kaplieva IV, Trepitaki LK, Galina AV. About the blood characteristics and adaptation status variability in intact Balb/c mice of different sex. South Russian Journal of Cancer. 2023;4(4):13-22. https://doi.org/10.37748/2686-9039-2023-4-4-2, EDN: DQDKII

21. Singh SB, Lin HC. Role of Intestinal Alkaline Phosphatase in Innate Immunity. Biomolecules. 2021 Nov 29;11(12):1784. https://doi.org/10.3390/biom11121784

22. Manchia M, Comai S, Pinna M, Pinna F, Fanos V, Denovan-Wright E, et al. Biomarkers in aggression. Adv Clin Chem. 2019;93:169–237. https://doi.org/10.1016/bs.acc.2019.07.004

23. Makushkina OA, Gurina OI, Golenkova VA. Biological basis of aggressive behavior. Neurology, Neuropsychiatry, Psychosomatics. 2021;13(5):76–82. (In Russ.). https://doi.org/10.14412/2074-2711-2021-5-76-82, EDN: VWKKYA

24. Markova EV. Behavior and immunity. Novosibirsk: Novosibirsk State Pedagogical University. 2013, 165 p. (In Russ.). EDN: SCWHZP

25. Krzych U, Thurman GB, Goldstein AL, Bressler JP, Strausser HR. Sex-related immunocompetence of BALB/c mice. I. Study of immunologic responsiveness of neonatal, weanling, and young adult mice. J Immunol. 1979 Dec;123(6):2568–2574.

26. Jacobsen H, Klein SL. Sex Differences in Immunity to Viral Infections. Front Immunol. 2021;12:720952. https://doi.org/10.3389/fimmu.2021.720952

27. Bakhmetyev BA. Age and sex differences in the formation of the immune system: connection with anthropometric data. Bulletin of the Orenburg Scientific Center of the Ural Branch of the Russian Academy of Sciences. 2016;(1):2. (In Russ.). EDN: VPZKCV

28. Ponomarenko GN, Turkovsky II. Biophysical foundations of physiotherapy: Textbook. Moscow: JSC "Publishing House "Medicine". 2006, 176 p. (In Russ.).

29. Kondepudi D, Prigogine I. Modern Thermodynamics: From Heat Engines to Dissipative Structures. Second Edition. John Wiley and Sons. 2014, 560 p.

30. Fehm HL, Kern W, Peters A. The selfish brain: competition for energy resources. Prog Brain Res. 2006;153:129–140. https://doi.org/10.1016/S0079-6123(06)53007-9

31. Linear Laboratory Mice C57Bl/6. BioPitomnik Stezar. [Internet] Available at: https://biopitomnik.ru/laboratornye-zhivotnye/linejnye-laboratornye-myshi-c57black-6.html, Assessed: 03/25/2023.

32. Tang X, Xiao J, Parris BS, Fang J, Sanford LD. Differential effects of two types of environmental novelty on activity and sleep in BALB/cJ and C57BL/6J mice. Physiol Behav. 2005 Jul 21;85(4):419–429. https://doi.org/10.1016/j.physbeh.2005.05.008

33. Hutchings C, Phillips JA, Djamgoz MBA. Nerve input to tumours: Pathophysiological consequences of a dynamic relationship. Biochim Biophys Acta Rev Cancer. 2020 Dec;1874(2):188411. https://doi.org/10.1016/j.bbcan.2020.188411

34. Kamiya A, Hiyama T, Fujimura A, Yoshikawa S. Sympathetic and parasympathetic innervation in cancer: therapeutic implications. Clin Auton Res. 2021 Apr;31(2):165–178. https://doi.org/10.1007/s10286-020-00724-y

35. Kostyuchenko LN, Kuz’mina TN. Strategy for accompanying nutritional support in digestive tract tumors: remaxol in the structure of nutritional and metabolic therapy in patients with extensive liver resections. P. A. Herzen Journal of Oncology. 2020;9(1):34–39. (In Russ.). https://doi.org/10.17116/onkolog2020901134

36. Moore FA, Phillips SM, McClain CJ, Patel JJ, Martindale RG. Nutrition Support for Persistent Inflammation, Immunosuppression, and Catabolism Syndrome. Nutr Clin Pract. 2017 Apr;32(1_suppl):121S–127S. https://doi.org/10.1177/0884533616687502

37. Chubenko VA, Moiseenko VM. Preclinical and clinical evidence of the prospects of metabolic cancer therapy. Practical oncology. 2022;23(1):51–60. (In Russ.). https://doi.org/10.31917/2301051

38. Lugtenberg RT, de Groot S, Kaptein AA, Fischer MJ, Kranenbarg EMK, Carpentier MD de, et al. Quality of life and illness perceptions in patients with breast cancer using a fasting mimicking diet as an adjunct to neoadjuvant chemotherapy in the phase 2 DIRECT (BOOG 2013-14) trial. Breast Cancer Res Treat. 2021 Feb;185(3):741–758. https://doi.org/10.1007/s10549-020-05991-x

39. Shatova OP, Kaplun DS, Zinkovych II. Metformin as target metabolic drug in oncology. Malignant Tumours. 2017;(2):83–89. (In Russ.). https://doi.org/10.18027/2224-5057-2017-2-83-89, EDN: ZXJOCL

40. Vancura A, Bu P, Bhagwat M, Zeng J, Vancurova I. Metformin as an Anticancer Agent. Trends Pharmacol Sci. 2018 Oct;39(10):867–878. https://doi.org/10.1016/j.tips.2018.07.006