Oxidative Stress Induced Alterations in Red Blood Cells and Their Role in Cardiovascular Pathophysiology

Aristoteles Aristoteles; Rosmiarti Asmar; Nurhi Dayanti

doi:10.31632/ijalsr.2026.v09i02.014

Aristoteles Aristoteles Universitas Muhammadiyah Ahmad Dahlan Palembang, Jl. Jendral Ahmad Yani 13 Ulu, Kec. Sebrang Ulu II, Kota Palembang, Indonesia https://orcid.org/0000-0003-0316-8450
Rosmiarti Asmar Universitas Muhammadiyah Ahmad Dahlan Palembang, Jl. Jendral Ahmad Yani 13 Ulu, Kec. Sebrang Ulu II, Kota Palembang, Indonesia https://orcid.org/0000-0001-9252-2751
Nurhi Dayanti Universitas Muhammadiyah Ahmad Dahlan Palembang, Jl. Jendral Ahmad Yani 13 Ulu, Kec. Sebrang Ulu II, Kota Palembang, Indonesia https://orcid.org/0000-0002-0018-4589

DOI https://doi.org/10.31632/ijalsr.2026.v09i02.014

Abstract

Introduction: Oxidative stress is a fundamental contributor to cardiovascular pathophysiology, primarily through excessive generation of reactive oxygen species (ROS) that disrupt cellular homeostasis. Red blood cells play a critical role in oxygen transport and redox balance; however, they are highly vulnerable to oxidative damage, which may impair their structural integrity and promote vascular dysfunction. Objective: This study aimed to examine oxidative stress-induced alterations in red blood cell parameters, antioxidant defence systems, and inflammatory responses, and to elucidate their potential role in cardiovascular pathophysiology. Methods: An experimental laboratory study was conducted using 30 male Wistar rats randomly assigned to control and oxidative stress groups. Oxidative stress was induced by intraperitoneal administration of hydrogen peroxide (H₂O₂) for 14 days. Haematological indices, including red blood cell count, haematocrit, and haemoglobin levels, were evaluated. Oxidative damage and antioxidant status were assessed by measuring malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Serum C-reactive protein (CRP) was analysed as an indicator of systemic inflammation. Data were analysed using independent t-tests with a significance level of α = 0.05. Results:The oxidative stress group demonstrated a significant decline in haematological parameters compared with the control group, including red blood cell count (5.98 ± 0.38 vs. 6.75 ± 0.41 ×10⁶/µL, p = 0.001), haematocrit (38.7 ± 3.2% vs. 43.5 ± 2.8%, p = 0.002), and haemoglobin concentration (12.5 ± 1.1 vs. 14.3 ± 0.9 g/dL, p = 0.001). Markers of oxidative damage were markedly elevated, as indicated by increased malondialdehyde levels (5.3 ± 1.0 vs. 2.1 ± 0.6 nmol/mL, p< 0.001). Conversely, antioxidant enzyme activities were significantly reduced in the oxidative stress group, including superoxide dismutase (1.92 ± 0.35 vs. 2.85 ± 0.43 U/mL, p< 0.001), catalase (32.6 ± 4.3 vs. 48.2 ± 5.1 U/mg protein, p< 0.001), and glutathione peroxidase (54.1 ± 7.4 vs. 71.4 ± 6.8 U/mL, p< 0.001). In addition, serum C-reactive protein levels were significantly higher in the oxidative stress group (4.9 ± 1.2 vs. 1.4 ± 0.7 mg/L, p< 0.001), indicating enhanced systemic inflammation. Conclusion: Oxidative stress induces pronounced alterations in red blood cell integrity, suppresses antioxidant defence mechanisms, and triggers systemic inflammation. These changes represent key early events in cardiovascular pathophysiology and highlight erythrocyte-related oxidative biomarkers as potential indicators for cardiovascular risk assessment.

Keywords: Antioxidant Enzymes, Cardiovascular Pathophysiology, Inflammation, Oxidative Stress, Red Blood Cells

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References

Abdelazim, A. M., & Abomughaid, M. M. (2024). Oxidative stress: An overview of past research and future insights. All Life, 17(1), 2316092. https://doi.org/10.1080/26895293.2024.2316092
Alfhili, M. A., Alghareeb, S. A., Alotaibi, G. A., & Alsughayyir, J. (2024). Galangin triggers eryptosis and hemolysis through Ca2+ nucleation and metabolic collapse mediated by PKC/CK1α/COX/p38/Rac1 signaling axis. International Journal of Molecular Sciences, 25(22), 12267. https://doi.org/10.3390/ijms252212267
Amponsah-Offeh, M., Diaba-Nuhoho, P., Speier, S., & Morawietz, H. (2023). Oxidative stress, antioxidants and hypertension. Antioxidants, 12(2), 281. https://doi.org/10.3390/antiox12020281
Aristoteles, Shatriadi, H., Haryoko, I., & Poddar, S. (2021). Comparative study of examination of LED value using the wintrobe method and hemoglobin examination using the sahli method on rattus norvegicus Wistar Exposed to Cigarette Smoke. Malaysian Journal of Medicine & Health Sciences. https://medic.upm.edu.my/upload/dokumen/2021061711264702_MJMHS_1219.pdf
Aristoteles., Sansuwito, T., ., B., & ., N. (2024). The Comparative study of physical exercise towards Brain Natriuretic Peptide (BNP) and Malondialdehyde (MDA) as oxidative stress markers in rattus novergicus wistar strain rats. International Journal of Advancement in Life Sciences Research, 7(2), 170-177. https://doi.org/10.31632/ijalsr.2024.v07i02.014
Awashra, A., AbuBaha, M., Mahafdah, B., AbuBaha, B., Aldwaik, S., Khaled, A., ... & Shubietah, A. (2026). Iron balance and cardiovascular health: the double-edged role of deficiency and overload. Cardiovascular Toxicology, 26, 9. https://doi.org/10.1007/s12012-025-10086-4
Cordiano, R., Di Gioacchino, M., Mangifesta, R., Panzera, C., Gangemi, S., & Minciullo, P. L. (2023). Malondialdehyde as a potential oxidative stress marker for allergy-oriented diseases: an update. Molecules, 28(16), 5979. https://doi.org/10.3390/molecules28165979
Di Franco, M., Vona, R., Gambardella, L., Cittadini, C., Favretti, M., Gioia, C., ... & Pietraforte, D. (2022). Estrogen receptors, ERK1/2 phosphorylation and reactive oxidizing species in red blood cells from patients with rheumatoid arthritis. Frontiers in Physiology, 13, 1061319. https://doi.org/10.3389/fphys.2022.1061319
dos Santos, J. L., de Quadros, A. S., Weschenfelder, C., Garofallo, S. B., & Marcadenti, A. (2020). Oxidative stress biomarkers, nut-related antioxidants, and cardiovascular disease. Nutrients, 12(3), 682. https://doi.org/10.3390/nu12030682
El Hoss, S., Lizarralde‐Iragorri, M. A., Maciel, T. T., & Hermine, O. (2026). Erythropoiesis in health and disease: Distinguishing defective and ineffective erythropoiesis. HemaSphere, 10(1), e70297. https://doi.org/10.1002/hem3.70297
Ghosh, A., & Shcherbik, N. (2020). Effects of oxidative stress on protein translation: Implications for cardiovascular diseases. International Journal of Molecular Sciences, 21(8), 2661. https://doi.org/10.3390/ijms21082661
Gusnirwan, A., & Sangging, P. R. A. (2024). Tinjauan: Malondialdehyde (MDA) sebagai Marker Stres Oksidatif Berbagai Penyakit. Medical Profession Journal of Lampung, 14(2), 321-325. https://doi.org/10.53089/medula.v14i2.990
Gwozdzinski, K., Pieniazek, A., & Gwozdzinski, L. (2021). Reactive oxygen species and their involvement in red blood cell damage in chronic kidney disease. Oxidative Medicine and Cellular Longevity, 2021(1), 6639199. https://doi.org/10.1155/2021/6639199
Krishnamurthy, H. K., Pereira, M., Rajavelu, I., Jayaraman, V., Krishna, K., Wang, T., ... & Rajasekaran, J. J. (2024). Oxidative stress: fundamentals and advances in quantification techniques. Frontiers in Chemistry, 12, 1470458. https://doi.org/10.3389/fchem.2024.1470458
Kurt, B., Reugels, M., Schneider, K. M., Spiesshoefer, J., Milzi, A., Gombert, A., ... & Kahles, F. (2025). C-reactive protein and cardiovascular risk in the general population. European Heart Journal, ehaf937. https://doi.org/10.1093/eurheartj/ehaf937
Kwon, G., Gibson, K. M., & Bi, L. (2024). Editorial Commentary on the Special Issue “Antioxidant Therapy for Cardiovascular Diseases”—Cutting-Edge Insights into Oxidative Stress and Antioxidant Therapy in Cardiovascular Health. Antioxidants, 13(9), 1034. https://doi.org/10.3390/antiox13091034
Martínez-Vieyra, I., Hernández-Rojo, I., Rosales-García, V. H., Chávez-Piña, A. E., & Cerecedo, D. (2025). Oxidative stress and cytoskeletal reorganization in hypertensive erythrocytes. Antioxidants, 14(1), 5. https://doi.org/10.3390/antiox14010005
Nashrullah, M., Fahyuni, E. F., Nurdyansyah, N., & Untari, R. S. (2023). Metodologi Penelitian Pendidikan (Prosedur Penelitian, Subyek Penelitian, Dan Pengembangan Teknik Pengumpulan Data). In Metodologi Penelitian Pendidikan (Prosedur Penelitian, Subyek Penelitian, Dan Pengembangan Teknik Pengumpulan Data) [Educational Research Methodology (Research Procedures, Research Subjects, and Development of Data Collection Techniques). In Educational Research Methodology (Research Procedures, Research Subjects, and Development of Data Collection Techniques)].Umsida Press, 1–64. https://doi.org/10.21070/2023/978-623-464-071-7
Ngadiman, N., Heza, F. N., & Wahono, B. S. (2023). Pengaruh Pemberian Vitamin E Terhadap Derajat Stress Oksidatif Akibat Olahraga. Physical Activity Journal (PAJU), 4(2), 269-280. https://doi.org/10.20884/1.paju.2023.4.2.8477
Nosalski, R., Siedlinski, M., Neves, K. B., & Monaco, C. (2024). The interplay between oxidative stress, immune cells and inflammation in cardiovascular diseases. Frontiers in Cardiovascular Medicine, 11, 1385809. https://doi.org/10.3389/fcvm.2024.1385809
Wahyu, A. E. N., Idris, I., Aras, D., Sinrang, A. W., Patellongi, I., & Nawir, N. (2023). Analysis of changes in Malondialdehyde (MDA) and Lactate Dehydrogenase (LDH) levels after a 30 km cycling event in the makassar cycling community. COMPETITOR: Jurnal Pendidikan Kepelatihan Olahraga, 15(1), 104. https://doi.org/10.26858/cjpko.v15i1.43630
Obeagu, E. I., Igwe, M. C., & Obeagu, G. U. (2024). Oxidative stress’s impact on red blood cells: Unveiling implications for health and disease. Medicine, 103(9), e37360. https://doi.org/10.1097/MD.0000000000037360
Pereira, C. P. M., Souza, A. C. R., Vasconcelos, A. R., & Prado, P. S. (2021). Antioxidant and anti inflammatory mechanisms of action of astaxanthin in cardiovascular diseases. International Journal of Molecular Medicine, 47(1), 37-48. https://doi.org/10.3892/ijmm.2020.4783
Pereira, M. (2024). No Title. February, 0–2. https://doi.org/10.14293/PR2199.000699.v1
Sadasivam, N., Kim, Y. J., Radhakrishnan, K., & Kim, D. K. (2022). Oxidative stress, genomic integrity, and liver diseases. Molecules, 27(10), 3159. https://doi.org/10.3390/molecules27103159
Tripathi, R. (2024). Antioxidants : Types , Functions and Usage. International Journal of Scientific Research In Science and Technology, 11(6), 442–454. https://doi.org/10.32628/IJSRST24114308
Tugasworo, D., Prasetyo, A., Kurnianto, A., Retnaningsih, R., Andhitara, Y., Ardhini, R., & Budiman, J. (2023). Malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in ischemic stroke: A systematic review. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery, 59(1), 87. https://doi.org/10.1186/s41983-023-00688-6
Tutino, V., De Nunzio, V., Donghia, R., Aloisio Caruso, E., Cisternino, A. M., Iacovazzi, P. A., ... & Notarnicola, M. (2024). Significant increase in oxidative stress indices in erythrocyte membranes of obese patients with metabolically-associated fatty liver disease. Journal of Personalized Medicine, 14(3), 315. https://doi.org/10.3390/jpm14030315
Valaitienė, J., & Laučytė-Cibulskienė, A. (2024). Oxidative stress and its biomarkers in cardiovascular diseases. Artery Research, 30(1), 18. https://doi.org/10.1007/s44200-024-00062-8
Wang, Y., Luo, D., Jiang, H., Song, Y., Wang, Z., Shao, L., & Liu, Y. (2023). Effects of physical exercise on biomarkers of oxidative stress in healthy subjects: A meta-analysis of randomized controlled trials. Open Life Sciences, 18(1), 20220668. https://doi.org/10.1515/biol-2022-0668
Yi, X., Zhu, Q. X., Wu, X. L., Tan, T. T., & Jiang, X. J. (2022). Histone methylation and oxidative stress in cardiovascular diseases. Oxidative Medicine and Cellular Longevity, 2022(1), 6023710. https://doi.org/10.1155/2022/6023710