volume | PIER Journals

Abstract

Sepsis is a life-threatening infectious disease. Mitochondrial dysfunction is widespread in severe sepsis. The myocardium contains a large number of mitochondria, and the survival rate of sepsis decreases sharply when cardiac dysfunction is involved. Vericiguat (BAY 1021189) is a novel drug for the prevention of heart failure. In this study, we evaluated the mitochondrial function of septic mice and drug-treated mice by resonance Raman spectroscopy (RRS). RRS can accurately identify the Raman characteristic peak at 750 cm^-1, 1128 cm^-1 and 1585 cm^-1 attributed to the reduced cytochrome in septic mice. We found that the intensity of the characteristic peak was significantly decreased in septic mice, indicating an imbalance of mitochondrial redox function, while the function was improved in the drug-treated group. It proves that BAY has the potential as a novel treatment for mitochondrial dysfunction in sepsis.

1. Picard, M. and O. S. Shirihai, "Mitochondrial signal transduction," Cell Metab, Vol. 34, No. 11, 1620-1653, 2022.
doi:10.1016/j.cmet.2022.10.008

2. Singer, M., C. S. Deutschman, C. W. Seymour, et al. "The third international consensus definitions for sepsis and septic shock (Sepsis-3)," Journal of Electromagnetic Waves and Applications, Vol. 315, No. 8, 801-810, 2016.

3. Navarrete, M. L., M. C. Cerdeño, M. C. Serra, et al. "Mitochondrial and microcirculatory distress syndrome in the critical patient," Med Intensiva, 2013, Vol. 37, No. 7, 476-484.
doi:10.1016/j.medin.2013.03.001

4. Galley, H. F., "Oxidative stress and mitochondrial dysfunction in sepsis," Br J. Anaesth, Vol. 107, No. 1, 57-64, 2011.
doi:10.1093/bja/aer093

5. Liaudet, L., N. Rosenblatt-Velin, and P. Pacher, "Role of peroxynitrite in the cardiovascular dysfunction of septic shock," Curr Vasc Pharmacol, Vol. 11, No. 2, 196-207, 2013.

6. Armstrong, P. W., B. Pieske, K. J. Anstrom, J. Ezekowitz, et al. "Vericiguat in patients with heart failure and reduced ejection fraction," N. Engl. J. Med., Vol. 82, No. 20, 1883-1893, 2020.
doi:10.1056/NEJMoa1915928

7. Sandner, P., D. P. Zimmer, G. T. Milne, et al. "Soluble guanylate cyclase stimulators and activators," Handb. Exp. Pharmacol., Vol. 264, 355-394, 2021.

8. Castora, F. J., "Mitochondrial function and abnormalities implicated in the pathogenesis of ASD," Prog Neuropsychopharmacol Biol Psychiatry, Vol. 92, 83-108, 2019.
doi:10.1016/j.pnpbp.2018.12.015

9. Galley, H. F., "Oxidative stress and mitochondrial dysfunction in sepsis," Br J. Anaesth, Vol. 107, 57-64, 2011.
doi:10.1093/bja/aer093

10. Carre, J. E., J. C. Orban, L. Re, K. Felsmann, W. Iffert, M. Bauer, et al. "Survival in critical illness is associated with early activation of mitochondrial biogenesis," Am J Respir Crit Care Med., Vol. 182, 745-751, 2010.
doi:10.1164/rccm.201003-0326OC

11. Jiao, C., Z. Lin, Y. Xu, and S. He, "Noninvasive raman imaging for monitoring mitochondrial redox state in septic rats," Progress In Electromagnetics Research, Vol. 175, 149-157, 2022.
doi:10.2528/PIER22101504

12. Zhang, C., A. Yang, and S. He, "Lateral flow immunoassay strip based on confocal raman imaging for ultrasensitive and rapid detection of covid-19 and bacterial biomarkers," Progress In Electromagnetics Research M, Vol. 120, 41-54, 2023.
doi:10.2528/PIERM23101104

13. Luo, J., Z. Lin, Y. Xing, E. Forsberg, C. Wu, X. Zhu, T. Guo, G. Wang, B. Bian, D. Wu, and S. He, "Portable 4D snapshot hyperspectral imager for fastspectral and surface morphology measurements," Progress In Electromagnetics Research, Vol. 173, 25-36, 2022.
doi:10.2528/PIER22021702

14. Xing, Y., C. Wang, T. Zhang, F. Shen, L. Meng, L. Wang, F. Li, Y. Zhu, Y. Zheng, N. He, and S. He, "VOC detections with optical spectroscopy," Progress In Electromagnetics Research, Vol. 173, 71-92, 2022.
doi:10.2528/PIER22033004

15. Lalonde, J. W., G. D. Noojin, N. J. Pope, S. M. Powell, V. V. Yakovlev, and M. L. Denton, "Continuous assessment of metabolic activity of mitochondria using resonance Raman microspectroscopy," Journal of Biophotonics, Vol. 14, e202000384, 2021.
doi:10.1002/jbio.202000384

16. Morimoto, T., L. D. Chiu, H. Kanda, H. Kawagoe, T. Ozawa, M. Nakamura, et al. "Using redox-sensitive mitochondrial cytochrome Raman bands for label-free detection of mitochondrial dysfunction," Analyst, Vol. 144, 2531-2540, 2019.
doi:10.1039/C8AN02213E

17. Jiao, C., Z. Lin, Y. Xu, and S. He, "Noninvasive raman imaging for monitoring mitochondrial redox state in septic rats," Progress In Electromagnetics Research, Vol. 175, 149-157, 2022.
doi:10.2528/PIER22101504

18. Brazhe, N. A., M. Treiman, B. Faricelli, J. H. Vestergaard, and O. Sosnovtseva, "In situ Raman study of redox state changes of mitochondrial cytochromes in a perfused rat heart," PLoS ONE, Vol. 8, e70488, 2013.
doi:10.1371/journal.pone.0070488

19. Chen, Z., J. Liu, L. Tian, Q. Zhang, Y. Guan, L. Chen, et al. "Raman micro-spectroscopy monitoring of cytochrome c redox state in Candida utilis during cell death under low-temperature plasma-induced oxidative stress," Analyst, Online ahead of print, 2020.

20. Morimoto, T., L. D. Chiu, H. Kanda, H. Kawagoe, T. Ozawa, M. Nakamura, et al. "Using redox-sensitive mitochondrial cytochrome Raman bands for label-free detection of mitochondrial dysfunction," Analyst, Vol. 144, 2531-2540, 2019.
doi:10.1039/C8AN02213E

21. Shao, J., M. Lin, Y. Li, X. Li, J. Liu, J. Liang, and H. Ya, "In vivo blood glucose quantification using raman spectroscopy," Plos One, Vol. 7, No. 10, e48127, 2012.
doi:10.1371/journal.pone.0048127

22. Brazhe, N. A., M. Treiman, B. Faricelli, J. H. Vestergaard, and O. Sosnovtseva, "In situ Raman study of redox state changes of mitochondrial cytochromes in a perfused rat heart," PLoS ONE, Vol. 8, e70488, 2013.
doi:10.1371/journal.pone.0070488

Dr. Xiaoxiao Zhao

Dr. Anqi Yang

Dr. Guangbin Zheng

Dr. Ronhai Lin

Dr. Yinghe Xu

Prof. Sailing He