Authors
- Tymoshenko Yana Evgenievna
Annotation
Considering the prooxidant effect of Fe2+ in blood plasma and its active reservation in hepatocytes, one could expect a high level of effectiveness of chelation therapy
for the correction of ischemia-reperfusion liver injury. The aim of the experimental study was a comparative assessment of the protective effect of selective and non-selective metal ion chelators in ischemia-reperfusion of the rat liver. The study was conducted on ten groups of rats (10 animals in each): the first group was a control group, five groups of animals with modeling of partial vascular isolation of the liver for 40 minutes and subsequent blood sampling 5, 30, 60, 120 or 180 minutes after blood flow restoration, and four groups were experimental, which were administered 0.5 ml of: physiological solution, 0.2 % sodium EDTA solution, 0.4 % sodium EDTA solution, deferoxamine solution at a dosage of 50 mg/kg before ischemia. The concentration of serum Fe2+, available for determination after modeling ischemiareperfusion damage to the organ for 180 minutes, did not change. During this period, the content of ferritin in the blood serum increased with a peak concentration of 10–13 times 60 minutes after blood flow restoration. Modulation of labile iron levels under oxidative stress conditions is a potential therapeutic strategy for preventing non-specific oxidative damage. Deferoxamine administration was accompanied by a 2.1-fold decrease in alanine aminotransferase, 2.6-fold decrease in aspartate aminotransferase, and 2.3-fold decrease in lactate dehydrogenase compared to the saline group. Administration of 0.2 % EDTA solution had a less pronounced protective effect. The protective effect of chelators, especially deferoxamine, was accompanied by normalization of laboratory parameters of oxidative stress, which acts as a leading pathobiochemical link in the implementation of ischemia-reperfusion syndrome. Determination of the cytoprotective activity of metal ion chelators under conditions of modeling partial liver ischemia-reperfusion clearly demonstrated the advantage of the selective iron ion chelator, deferoxamine, over the non-selective EDTA.
How to link insert
Tymoshenko, Y. E. (2024). POSSIBILITIES OF USING SELECTIVE CHELATION THERAPY TO CORRECT PATHOBIOCHEMICAL CHANGES IN EXPERIMENTAL ISCHEMIA-REPERFUSION INJURY OF THE LIVER Bulletin of the Moscow City Pedagogical University. Series "Pedagogy and Psychology", № 4 (56), 32. https://doi.org/10.24412/2076-9091-2024-456-32-43
References
1.
1. Popov K. A., Bykov I. M., Tsymbalyuk I. Yu., Bykov M. I., Azimov E. A., Stolyarova A. N., Timoshenko Ya. E. Pathobiochemistry of ischemic-reperfusion liver
injuries: monograph / ed. K. A. Popova, I. M. Bykova. Krasnodar: Quality LLC. 2023. 212 p. (In Russ.).
2.
2. Adel N., Mantawy E. M., El-Sherbiny D. A. Iron chelation by deferasirox confers protection against concanavalin A-induced liver fibrosis: A mechanistic approach. Toxicology and Applied Pharmacology. 2019;382(1):114748. https://doi.org/10.1016/j.taap.2019.114748
3.
3. Ali F., Abo-Youssef A., Messiha B., Hemeida R. Hepatic Ischemia Reperfusion Injury: Pathophysiology and Therapeutic Strategies. Pharm. J. of Innovative Drug R&D. 2016;1(2):45–61.
4.
4. Arkadopoulos N., Nastos C., Kalimeris K. Iron chelation for amelioration of liver ischemia-reperfusion injury. Hemoglobin. 2010;34(3):265–277. https://doi.org/10.3109/03630269.2010.484766
5.
5. Han D., Kang Si.‑H., Yoon C.-H., Youn T.-J., Chae I.-H. Attenuation of ischemia-reperfusion injury by intracoronary chelating agent administration. Scientific reports. 2022;12(1):2050. https://doi.org/10.1038/s41598-022-05479-2
6.
6. Ikeyama Y., Sato T., Takemura A., Sekine S., Ito K. Hypoxia/reoxygenation exacerbates drug-induced cytotoxicity by opening mitochondrial permeability transition pore: possible application for toxicity screening. Toxicology In Vitro. 2020;67:104889. https://doi.org/10.1016/j.tiv.2020.104889
7.
7. Luoa S., Luoa R., Denga G., Huanga F., Leia Z. Programmed cell death, from liver Ischemia-Reperfusion injury perspective: An overview. Неliyon. 2024;10(13):32480. https://doi.org/10.3109/03630269.2010.484766
8.
8. Mantelou A. G., Barbouti A., Goussia A., Zacharioudaki A. Combined administration of membrane-permeable and impermeable iron-chelating drugs attenuates ischemia/reperfusion-induced hepatic injury. Free Radical Biology and Medicine. 2022;193(1):227–237. https://doi.org/10.1016/j.freeradbiomed.2022.10.266
9.
9. Nastos C., Kalimeris K., Papoutsidakis N., Tasoulis M.-K., Lykoudis P. M., Theodoraki K., Nastou D., Smyrniotis V., Arkadopoulos N. Global Consequences of Liver Ischemia/Reperfusion Injury. Oxidative Medicine and Cellular Longevity. 2014:906965. https://doi.org/10.1155/2014/906965
10.
10. Nousis L., Kanavaros P., Barbouti A. Oxidative Stress-Induced Cellular Senescence: Is Labile Iron the Connecting Link? Antioxidants. 2023;12(6):1250. https://doi.org/10.3390/antiox12061250
11.
11. Ovalle R. A History of the Fenton Reactions (Fenton Chemistry for Beginners). Reactive Oxygen Species. 2022;67:11. https://doi.org/10.5772/intechopen.99846
12.
12. Tian C., Wang A., Huang H., Chen Y. Effects of remote ischemic preconditioning in hepatectomy: a systematic review and meta-analysis. BMC Anesthesiology. 2024;24(118):13. https://doi.org/10.1186/s12871-024-02506-9
13.
13. Yamadа N., Karasawa T. , Wakiya T., Sadatomo A., Ito H., Kamata R., Watanabe S., Komada T., Kimura H., Sanada Y., Sakuma Y., Mizuta K., Ohno N., Sata N., Takahashi M. Iron overload as a risk factor for hepatic ischemia-reperfusion injury in liver transplantation: Potential role of ferroptosis // American Journal of Transplantation. 2020;20(6):1606–1618. https://doi.org/10.1111/ajt.15773
14.
14. Zdujic P., Bogdanovic A., Djindjic U., Kovac J. D., Basaric D., Zdujic N., Dugalic V. Impact of prolonged liver ischemia during intermittent Pringle maneuver on postoperative outcome following liver resection. Asian Journal of Surgery. 2024;47(8):3485–3491. https://doi.org/10.1016/j.asjsur.2024.03.005
15.
15. Zhang C. H., Yan Yu.-J., Luo Q. The molecular mechanisms and potential drug targets of ferroptosis in myocardial ischemia–reperfusion injury. Life Sciences. 2024;340(1):122439. https://doi.org/10.1016/j.lfs.2024.122439