HYDROGEN SULFIDE METABOLISM PARAMETERS IN THE RAT BRAIN UNDER CONDITIONS OF ACUTE CEREBRAL ISCHEMIA AND PHARMACOLOGICAL CORRECTION

Authors

DOI:

https://doi.org/10.11603/mcch.2410-681X.2026.i2.16262

Keywords:

cerebral ischemia; citicoline; hydrogen sulfide; metabolism; brain; rats.

Abstract

Introduction. The severe epidemiological situation regarding ischemic strokes is partly due to unresolved issues in pharmacotherapy. The role of the hydrogen sulfide (H2S) system in the mechanisms of action of known neuroprotective agents and the modification of their pharmacological activity remains insufficiently studied. The aim of the study – to evaluate the indices of H2S metabolism in the rat brain under conditions of acute cerebral ischemia and against the background of treatment with citicoline and its combination with H2S metabolic modulators. Research Methods. The study was conducted on 75 adult male rats divided into 5 groups: Group 1 – sham- operated animals; Groups 2–5 – modeled acute cerebral ischemia; Groups 3–5 – treated with citicoline for one week; Groups 4 and 5 – received an H2S donor (sodium hydrosulfide, NaHS) and a synthesis inhibitor (aminooxyacetate, AOA), respectively, in addition to citicoline for 7 days. In the brain homogenate, H2S content, as well as the activity of its synthesis, deposition, and utilization processes, were determined. Statistical analysis was performed using the SPSS Statistics 17.0 software package. Results and Discussion. Pharmacotherapy of acute cerebral ischemia with citicoline is accompanied by the replenishment of H2S stores, improvement of its sequestration (deposition), enhancement of enzymatic synthesis, and inhibition of oxidative degradation in the rat brain. The applied H2S modulators exert multidirectional effects on the ability of citicoline to correct H2S metabolism during acute cerebrovascular accidents: NaHS potentiates these effects of citicoline, whereas AOA exhibits the opposite effect. Conclusions. The combination of citicoline and NaHS demonstrates the most pronounced corrective effect on H2S metabolism in the rat brain under conditions of acute cerebral ischemia.

References

Global burden of cardiovascular diseases: projections from 2025 to 2050 (2025). Eur J Prev Cardiol., 32(11), 1001–1015. https://doi.org/10.1093/eurjpc/ zwae281.

GBD 2019 Stroke Collaborators (2021). Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol., 20(10), 795–820. https://doi.org/10.1016/S1474-4422(21)00252-0.

Salaudeen, M. A., Bello, N., Danraka, R. N., & Ammani, M. L. (2024). Understanding the Pathophysiology of Ischemic Stroke: The Basis of Current Therapies and Opportunity for New Ones. Biomolecules, 14(3), 305. https://doi.org/10.3390/biom14030305.

Karimulin, R. F., & Semenenko, A. I. (2023). Effect of different combinations of neuroprotectors on neurological deficit, motor and orientation-research activity, cognitive functions during experimental ischemic stroke. Reports of Vinnytsia National Medical University, 27(3), 372–376. https://doi.org/10.31393/reports- vnmedical-2023-27(3)-03 [in Ukrainian].

Secades, J. J., & Gareri, P. (2022). Citicoline: pharmacological and clinical review, 2022 update. Citicolina: revisión farmacológica y clínica, actualización 2022. Revista de neurologia, 75(s05), 1–89. https://doi. org/10.33588/rn.75s05.2022311.

Sokrateva, T., Roussev, B., Vankova, D. V., Vankova, D. G., Ivanova, D., Tsalta-Mladenov, M., … & Nashar, M. A. (2026). Effects of Citicoline-Based Supplementation on Lipid Peroxidation Markers and Sirtuin-1 Expression in Ischemic Stroke. Current issues in molecular biology, 48(3), 314. https://doi.org/10.3390/ cimb48030314.

Ding, J. S., Zhang, Y., Wang, T. Y., Li, X., Ma, C., Xu, Z. M., … & Chen, G. (2023). Therapeutic applications of hydrogen sulfide and novel donors for cerebral ischemic stroke: a narrative review. Medical gas research, 13(1), 7–9. https://doi.org/10.4103/2045-9912.350863.

Percie du Sert, N., Hurst, V., Ahluwalia, A., Alam, S., Avey, M. T., Baker, … & Würbel, H. (2020). The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. British Journal of Pharmacology, 177(16), 3617–3624. https://doi.org/10.1111/bph.15193.

Konovalov, S. V., Konovalova, N. V., & Husakova, I. V. (2025). Protective effect of citicoline in acute reversible cerebral ischemia in rats. Bukovinian Medical Herald, 29(2 [114]), 16–21). https://doi.org/10.24 061/2413-0737.29.2.114.2025.3 [in Ukrainian].

Yurchenko, P. O., & Zaichko, N. V. (2015). Biochemical changes in rats’ brain with isolated hyperhomocysteinemia in modulation of hydrogen sulfide metabolism. Medical Сhemistry, 17(1), 17–21). https://doi.org/10.11603/1681-2557.2015.v17.i1.4066. [in Ukrainian].

Wiliński, B., Wiliński, J., Somogyi, E., Piotrowska, J., & Góralska, M. (2011). Atorvastatin affects the tissue concentration of hydrogen sulfide in mouse kidneys and other organs. Pharmacological reports, 63(1), 184–188. DOI: https://doi.org/10.1016/ s1734-1140(11)70414-5.

Melnik, A.V., & Pentiuk, O.O. (2009). Activity of hydrogen sulfide production enzymes in kidneys of rats. Ukrainian Biochemical Journal, 81(4), 12-23. [in Ukrainian].

Yurchenko, P.О. (2015). Effect of Isolated Hyperhomocysteinemia on Hydrogen Sulfide System in Rats’ Brain. Bulletin of problems biology and medicine, 2(3), 252-256. http://nbuv.gov.ua/UJRN/ Vpbm_2015_2%283%29__58. [in Ukrainian].

Jung, H. I., Lim, H. W., Kim, B. C., Park, E. H., & Lim, C. J. (2004). Differential thioredoxin reductase activity from human normal hepatic and hepatoma cell lines. Yonsei Medical Journal, 45(2), 263–272. https://doi. org/10.3349/ymj.2004.45.2.263.

Lowry, O. H., Rosebrough, N. J., Farr, A. L., & Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. The Journal of biological chemistry, 193(1), 265–275. Retrieved from: https://www.jbc.org/ article/S0021-9258(19)52451-6/pdf.

Cirino G, Szabo C, & Papapetropoulos A. (2023). Physiological roles of hydrogen sulfide in mammalian cells, tissues, and organs, Physiol Rev, 103(1), 31-276. https://doi.org/10.1152/physrev.00028.2021.

Wu, D., Pan, J., Fang, X., & Chen, Z. (2025). Comparison of the effects of citicoline and vascular rehabilitation capsules on neurotrophic and inflammatory factors in patients with cerebral infarction. Journal of medical biochemistry, 44(4), 724–730. https://doi. org/10.5937/jomb0-55775.

Sahraiian, V., & Khazali, H. (2021). Ghrelin Is Effective on Passive Avoidance Memory by Altering the Expression of NMDAR and HTR1a Genes in the Hippocampus of Male Wistar Rats. Reports of biochemistry & molecular biology, 10(3), 380–386. https:// doi.org/10.52547/rbmb.10.3.380

Published

2026-05-27

Issue

Section

ORIGINAL INVESTIGATIONS

How to Cite

HYDROGEN SULFIDE METABOLISM PARAMETERS IN THE RAT BRAIN UNDER CONDITIONS OF ACUTE CEREBRAL ISCHEMIA AND PHARMACOLOGICAL CORRECTION. (2026). Medical and Clinical Chemistry, 2, 87-92. https://doi.org/10.11603/mcch.2410-681X.2026.i2.16262