Determining the probable role of ferroptosis in the course of inflammatory bacterial diseases of the respiratory organs in young children accompanied by the development of anemia of inflammation
DOI:
https://doi.org/10.14739/2310-1237.2021.1.229019Keywords:
ferroptosis, acute inflammatory diseases, anemia, young childrenAbstract
Aim. To determine the probable role of ferroptosis in the course of inflammatory bacterial diseases of the respiratory system in young children, accompanied by the development of anemia of inflammation.
Materials and methods. The study included 62 children (mean age 1.4 ± 0.4 years). The main group included 42 children with acute inflammatory bacterial diseases of the respiratory system, accompanied by anemia of inflammation: 29 children were diagnosed with bacterial bronchitis, 13 children – pneumonia. Determination of the severity of inflammatory diseases was determined by Acute Bronchitis Severity Score and Pediatric Respiratory Severity Score. At the time of participation in the study, all patients under observation had no signs of impaired iron metabolism, including iron deficiency anemia, in the anamnesis. The control group included 20 relatively healthy children. The content of caspase-7, caspase-9, ferritin, nitrotyrosine, phospholipase A2 was determined by ELISA using commercial kits.
Results. We hypothesized the ineffectiveness of apoptosis in the course of bacterial inflammatory processes of the respiratory organs in young children, accompanied by the development of anemia of inflammation, and studied the probability of ferroptosis in these conditions. The obtained data indicated the presence of active oxidative stress in the main group patients. The strong direct correlation between the severity of inflammatory disease and the intensity of oxidative stress was revealed (r = 0.7, P < 0.001). A statistically significant increase in ferritin content in the main group compared with the control group was observed. There was a strong direct correlation between ferritin levels and the severity of bronchitis (r = 0.82, P < 0.01) and the severity of pneumonia (r = 0.87, P < 0.01). It was found that the upper quartile of serum ferritin levels (73.2 ± 4.6 ng/ml) was associated with severe disease. We assumed that restriction of access to iron for bacterial pathogens due to its sequestration in cells is a pathological process under certain conditions.
Conclusions. In the pathogenesis of bacterial inflammatory diseases of the respiratory organs in young children, accompanied by the development of anemia of inflammation, the processes of apoptosis did not dominate, but, obviously, necrotic phenomena did, including ferroptosis as one of the manifestations of necrosis. The protective mechanism aimed at limiting the access of bacterial pathogens to iron due to its sequestration in cells becomes pathological under certain conditions.
References
Lewerenz, J., Ates, G., Methner, A., Conrad, M., & Maher, P. (2018). Oxytosis/Ferroptosis-(Re-) Emerging Roles for Oxidative Stress-Dependent Non-apoptotic Cell Death in Diseases of the Central Nervous System. Frontiers in neuroscience, 12, 214. https://doi.org/10.3389/fnins.2018.00214
Toyokuni, S., Yanatori, I., Kong, Y., Zheng, H., Motooka, Y., & Jiang, L. (2020). Ferroptosis at the crossroads of infection, aging and cancer. Cancer science, 111(8), 2665-2671. https://doi.org/10.1111/cas.14496
Dixon, S. J., Lemberg, K. M., Lamprecht, M. R., Skouta, R., Zaitsev, E. M., Gleason, C. E., Patel, D. N., Bauer, A. J., Cantley, A. M., Yang, W. S., Morrison, B., 3rd, & Stockwell, B. R. (2012). Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell, 149(5), 1060-1072. https://doi.org/10.1016/j.cell.2012.03.042
Stockwell, B. R., Friedmann Angeli, J. P., Bayir, H., Bush, A. I., Conrad, M., Dixon, S. J., Fulda, S., Gascón, S., Hatzios, S. K., Kagan, V. E., Noel, K., Jiang, X., Linkermann, A., Murphy, M. E., Overholtzer, M., Oyagi, A., Pagnussat, G. C., Park, J., Ran, Q., Rosenfeld, C. S., … Zhang, D. D. (2017). Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease. Cell, 171(2), 273-285. https://doi.org/10.1016/j.cell.2017.09.021
Vartanian A. A. (2017). Metabolizm zheleza, ferroptoz, rak [Iron metabolism, ferroptosis and cancer]. Russian Journal of Biotherapy, 16(3), 14-20. [in Russian]. https://doi.org/10.17650/1726-9784-2017-16-3-14-2020
Ishutina, N. A. (2013). Aktivnost' fosfolipazy A2 i sostoyanie protsessov perekisnogo okisleniya lipidov v perifericheskoi krovi u beremennykh s gerpes-virusnoi infektsiei [Activity phospholipase A2 and state of processes of peroxide oxidation of lipids in the peripheric blood at pregnant with the herpes-virus infection contamination]. Uspekhi sovremennogo estestvoznaniya, (2), 12-14. [in Russian].
Mwachari, C., Nduba, V., Nguti, R., Park, D. R., Sanguli, L., & Cohen, C. R. (2007). Validation of a new clinical scoring system for acute bronchitis. The international journal of tuberculosis and lung disease, 11(11), 1253-1259.
Miyaji, Y., Sugai, K., Nozawa, A., Kobayashi, M., Niwa, S., Tsukagoshi, H., Kozawa, K., Noda, M., Kimura, H. & Mori, M. (2015). Pediatric Respiratory Severity Score (PRESS) for Respiratory Tract Infections in Children. Austin Virol and Retrovirology, 2(1), 1009.
Lezhenko, H. O., Abramov, A. V., & Pohribna, A. O. (2019). The content of apoptosis mediators in children with anemia of inflammation acquired on the background of acute bacterial diseases of respiratory organs. Pathologia, 16(2), 177-181. https://doi.org/10.14739/2310.1237.2019.2.177112
Lezhenko, H. O., Abramov, A. V., Pohribna, A. O. (2019). Pathogenetic role of nitrosative and oxidative stress in the development of anemia of inflammation in young children. Zdorov'e rebenka, 14(8), 8-12. https://doi.org/10.22141/2224-0551.14.8.2019.190837
Kenny, E. M., Fidan, E., Yang, Q., Anthonymuthu, T. S., New, L. A., Meyer, E. A., Wang, H., Kochanek, P. M., Dixon, C. E., Kagan, V. E., & Bayir, H. (2019). Ferroptosis Contributes to Neuronal Death and Functional Outcome After Traumatic Brain Injury. Critical care medicine, 47(3), 410-418. https://doi.org/10.1097/CCM.0000000000003555
Yan, N., & Zhang, J. (2020). Iron Metabolism, Ferroptosis, and the Links With Alzheimer's Disease. Frontiers in neuroscience, 13, 1443. https://doi.org/10.3389/fnins.2019.01443
Lezhenko, H. O., & Pogribna, A. O. (2020). The role of hepcidin in the pathogenetic mechanisms of anemia of inflammation development in young children with acute inflammatory bacterial diseases of the respiratory system. Zaporozhye Medical Journal, 22(4), 473-478. https://doi.org/10.14739/2310-1210.2020.4.208356
Reznik, N. L. (2018). Ferroptoz [Ferroptosis]. Khimiya i zhizn', (10), 12-16. [in Russian].
Theil E. C. (2013). Ferritin: the protein nanocage and iron biomineral in health and in disease. Inorganic chemistry, 52(21), 12223-12233. https://doi.org/10.1021/ic400484n
Lal, A. (2020). Iron in Health and Disease: An Update. Indian journal of pediatrics, 87(1), 58-65. https://doi.org/10.1007/s12098-019-03054-8
Quiles Del Rey, M., & Mancias, J. D. (2019). NCOA4-Mediated Ferritinophagy: A Potential Link to Neurodegeneration. Frontiers in neuroscience, 13, 238. https://doi.org/10.3389/fnins.2019.00238
Lei, P., Bai, T., & Sun, Y. (2019). Mechanisms of Ferroptosis and Relations With Regulated Cell Death: A Review. Frontiers in physiology, 10, 139. https://doi.org/10.3389/fphys.2019.00139
Mao, H., Zhao, Y., Li, H., & Lei, L. (2020). Ferroptosis as an emerging target in inflammatory diseases. Progress in biophysics and molecular biology, 155, 20-28. https://doi.org/10.1016/j.pbiomolbio.2020.04.001
Amaral, E. P., Costa, D. L., Namasivayam, S., Riteau, N., Kamenyeva, O., Mittereder, L., Mayer-Barber, K. D., Andrade, B. B., & Sher, A. (2019). A major role for ferroptosis in Mycobacterium tuberculosis-induced cell death and tissue necrosis. The Journal of experimental medicine, 216(3), 556-570. https://doi.org/10.1084/jem.20181776
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