Effect of mitochondrial suspension injections on changes in serum biochemical parameters in rats with ischemic muscle damage

Limb ischemia is a severe form of damage to skeletal muscle tissue, which leads to decreased viability and dysfunction. Mitochondrial damage plays a key role in the development of skeletal muscle ischemia. Mitochondrial transplantation as a new effective therapeutic strategy for replacing defective mitochondria is expected to increase the viability and improve the functional state of damaged skeletal muscles. An analysis of changes in the levels of a number of biochemical parameters in the blood serum of Wistar rats with experimental ischemia of the hind limbs and during the correction of these pathologies using a suspension of mitochondria was carried out. Serum levels of creatinine, alanine aminotransferase, total creatine kinase, interleukin-6 and interleukin-10 were significantly increased during experimental hind limb ischemia in rats. Correction of damage in ischemic muscles using injections of a suspension of mitochondria had protective and reparative effects in damaged tissues, which caused changes in the biochemical parameters of blood serum towards normalization. Thus, peripheral ischemia is accompanied by hyperenzymemia and increased creatine kinase activity, while local administration of a mitochondrial suspension to site of injury produces pronounced cytoprotective and immunomodulatory effect.

1. Creager M. A., Kaufman J. A., Conte M. S. Acute limb ischemia. New England Journal of Medicine, 2012, vol. 366, no. 23, pp. 2198–2206. https://doi.org/10.1056/nejmcp1006054

2. Qadura M., Terenzi D. C., Verma S., Al-Omran M., Hess D. A. Concise review: cell therapy for critical limb ischemia: an integrated review of preclinical and clinical studies. Stem Cells, 2018, vol. 36, no. 2, pp. 161–171. https://doi.org/10.1002/stem.2751

3. Annex B. H. Therapeutic angiogenesis for critical limb ischaemia. Nature Reviews Cardiology, 2013, vol. 10, pp. 387–396. https://doi.org/10.1038/nrcardio.2013.70

4. Paradis S., Charles A.-L., Meyer A., Lejay A., Scholey J. W., Chakfé N., Zoll J., Geny B. Chronology of mitochondrial and cellular events during skeletal muscle ischemia-reperfusion. American Journal of Physiology-Cell Physiology, 2016, vol. 310, no. 11, pp. 968–982. https://doi.org/10.1152/ajpcell.00356.2015

5. Durhuus J. A., Desler C., Rasmussen L. J. Mitochondria in health and disease. Mitochondrion. 3rd Annual Conference of Society for Mitochondrial Research and Medicine, 19–20 December 2013, Bengaluru, India, 2015, vol. 20, pp. 7–12. https:// doi.org/10.1016/j.mito.2014.10.004

6. McCully J. D., Cowan D. B., Emani S. M., del Nido P. J. Mitochondrial transplantation: from animal models to clinical use in humans. Mitochondrion, 2017, vol. 34, pp. 127–134. https://doi.org/10.1016/j.mito.2017.03.004

7. Orfany A., Arriola C. G., Doulamis I. P., Guariento A., Ramirez-Barbieri G., Moskowitzova K., Shin B., Blitzer D., Rogers C., del Nido P. J., McCully J. D. Mitochondrial transplantation ameliorates acute limb ischemia. Journal of Vascular Surgery, 2020, vol. 71, no. 3, pp. 1014–1026. https://doi.org/10.1016/j.jvs.2019.03.079

8. Zhavoronok I. P., Fedorova E. V., Antipova O. A., Erofeeva A.-M. V. The effect of mitochondrial suspension on nociceptive sensitivity and reparative processes in ischemic tissue in experimental angiopathy. Novosti mediko-biologicheskikh nauk = News of Biomedical Sciences, 2023, vol. 23, no. 3, pp. 42–43 (in Russian).

9. Bogdan V., Doronkina A., Zhavoronok I., Fedorova E., Filippovich T., Lepeshko S., Mankovskaya S. Pathogenetic model of chronic arterial insufficiency of blood supply to a limb in an experiment. Khirurgiya. Vostochnaya Evropa = Surgery. Eastern Europe, 2024, vol. 13, no. 1, pp. 38–48 (in Russian).

10. Liao P.-C., Bergamini C., Fato R., Pon L. A., Pallotti F. Isolation of mitochondria from cells and tissues. Methods in Cell Biology, 2020, vol. 155, pp. 3–31. https://doi.org/10.1016/bs.mcb.2019.10.002

11. Gubich O. I. Medical Biochemistry. Practical Course. Minsk, 2014. 100 p. (in Russian).

12. Abrashova T. V., Guschin Ja. A., Kovaleva M. A., Rybakova A. V., Selezneva A. I., Sokolova A. P., Hodko S. V. Physiological, Biochemical and Biometric Parameters of Experimental Animals: a reference book. Saint Petersburg, 2013. 116 p. (in Russian).

13. Kaydash O. A., Ivanov V. V., Vengerovsky A. I., Buyko E. E., Schepetkin I. A. The experimental model of type 2 diabetes mellitus caused by a high-fat diet with low-dose streptozotocin in rats. Byulleten’ sibirskoi meditsiny = Bulletin of Siberian Medicine, 2020, vol. 19, no. 2, pp. 41–47. https://doi.org/10.20538/1682-0363-2020-2-41-47

14. Kidun K. A., Litvinenko A. N., Ugolnik T. S., Golubykh N. M., Solodova E. K. Changes of the biochemical parameters of the blood serum of Wistar rats exposed to chronic stres. Problemy zdorov’ya i ekologii = Health and Ecology Issues, 2019, no. 4, pp. 62–67 (in Russian). https://doi.org/10.51523/2708-6011.2019-16-4-12

15. Evdokimova N. E., Tsygankova O. V., Latyntseva L. D. Evaluation of plasma creatine phosphokinase as a diagnostic dilemma. Russkii meditsinskii zhurnal [Russian Medical Journal], 2021, vol. 29, no. 2, pp. 18–25 (in Russian).