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Linking oxidative stress biomarkers to disease progression and antioxidant therapy in hypertension and diabetes mellitus
Open accessAbstract
Oxidative stress (OS) is increasingly recognized as a key factor linking hypertension (HTN) and diabetes mellitus (DM). This review summarizes recent evidence regarding the dual role of OS as both an instigator and an amplifier of cardiometabolic dysfunction. In HTN, reactive oxygen species (ROS) produced by NADPH oxidases (NOXs) and mitochondrial dysfunction contribute to endothelial impairment and vascular remodeling. In DM, hyperglycemia-induced ROS production worsens beta-cell failure and insulin resistance through pathways such as the AGE-RAGE signaling, protein kinase C (PKC) activation, and the polyol pathway. Clinically validated biomarkers of OS, such as F2-isoprostanes (which indicate lipid peroxidation), 8-OHdG (which indicates DNA damage), and the activities of redox enzymes like superoxide dismutase (SOD) and glutathione peroxidase (GPx), show strong correlations with disease progression and end-organ complications. Despite promising preclinical results, the application of antioxidant therapies in clinical settings has faced challenges due to inconsistent outcomes, highlighting the need for targeted approaches. Emerging strategies include: 1. Mitochondria-targeted antioxidants to enhance vascular function in resistant HTN; 2. Nrf2 activators to restore redox balance in early diabetes; and 3. Specific inhibitors of NOX isoforms. We emphasize three transformative areas of research: (i) the interaction between the microbiome and ROS, where modifying gut microbiota can reduce systemic OS; (ii) the use of nanotechnology to deliver antioxidants directly to pancreatic islets or atherosclerotic plaques; and (iii) phenotype-specific diagnosis and therapy guided by redox biomarkers and genetic profiling (for example, KEAP1/NRF2 polymorphisms). Integrating these advances with lifestyle modifications, such as following a Mediterranean diet and exercising regularly, may provide additional benefits. This review outlines a mechanistic framework for targeting OS in the comorbidity of HTN and DM while identifying critical knowledge gaps, particularly regarding the timing of antioxidant signaling and the development of personalized redox medicine, which may serve as a reference for researchers and clinicians working in this area.
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“This supports the idea that lipid peroxidation markers may serve as mechanistically plausible candidate predictors; however, the present evidence base remains heterogeneous in marker selection, assay platform, and standardization, and direct comparative evidence against standard clinic-based models is still limited (20–22).”
From AI-driven cardiovascular risk prediction in patients with diabetes: bridging algorithmic innovation to equitable clinical application (2026) · cites this paper as [22]
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“This supports the idea that lipid peroxidation markers may serve as mechanistically plausible candidate predictors; however, the present evidence base remains heterogeneous in marker selection, assay platform, and standardization, and direct comparative evidence against standard clinic-based models is still limited (20–22).”
From AI-driven cardiovascular risk prediction in patients with diabetes: bridging algorithmic innovation to equitable clinical application (2026) · cites this paper as [22]
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“Oxidative stress plays a central role in the shared pathophysiology of diabetes and cardiovascular disease, with lipid peroxidation representing one of its major downstream consequences.”
From AI-driven cardiovascular risk prediction in patients with diabetes: bridging algorithmic innovation to equitable clinical application (2026) · cites this paper as [22]
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“Studies have shown that oxidized lipid products and related oxidative stress markers may reflect vascular injury, inflammatory activity, and cardiometabolic dysfunction (18–22).”
From AI-driven cardiovascular risk prediction in patients with diabetes: bridging algorithmic innovation to equitable clinical application (2026) · cites this paper as [22]
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“Moreover, integrating mechanistic biomarkers—such as those related to lipid peroxidation—holds potential to improve biological relevance and possibly predictive performance (18–22).”
From AI-driven cardiovascular risk prediction in patients with diabetes: bridging algorithmic innovation to equitable clinical application (2026) · cites this paper as [22]
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“The association between lipid peroxidation and diabetic cardiovascular complications has been extensively discussed in the literature (18, 19, 21, 22).”
From AI-driven cardiovascular risk prediction in patients with diabetes: bridging algorithmic innovation to equitable clinical application (2026) · cites this paper as [22]
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Cites
The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology
Bedard, K., & Krause, K.-H. (2007) · Physiological Reviews · doi:10.1152/physrev.00044.2005 · Cited by 6,989
Increased oxidative stress in obesity and its impact on metabolic syndrome
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Oxidative stress and diabetic complications
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Reactive oxygen species (ROS) as pleiotropic physiological signalling agents
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Oxidative Stress: Harms and Benefits for Human Health
Pizzino, G., Irrera, N., Cucinotta, M., Pallio, G., Mannino, F., Arcoraci, V., Squadrito, F., Altavilla, D., & Bitto, A. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/8416763 · Cited by 4,837
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Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases
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Activation of Protein Kinase C Isoforms and Its Impact on Diabetic Complications
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Cited by
Sorted by citations
Antioxidants and Reactive Oxygen Species: Shaping Human Health and Disease Outcomes
Manful, C. F., Fordjour, E., Subramaniam, D., Sey, A. A., Abbey, L., & Thomas, R. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26157520 · Cited by 193
Roy, B. (2025) · Medical Sciences · doi:10.3390/medsci13030087 · Cited by 103
Diaconescu, B. I., Dumitru, A. V., Tătaru, C. P., Toader, C., Șerban, M., Covache-Busuioc, R.-A., & Eva, L. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262210835 · Cited by 25
Chen, Y., Zhu, J., Gui, H., Liu, M., Zhang, Y., Wu, Z., Liu, C., & Wang, M. (2026) · Antioxidants · doi:10.3390/antiox15070803 · Cited by 8
Martinc, B. (2026) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2026.113197 · Cited by 5
Metadata
- Authors
- Nuñez-Selles, A. J., Nuñez-Musa, R. A., & Guillen-Marmolejos, R. A.
- Venue
- Frontiers in Molecular Biosciences
- Publisher
- Frontiers Media SA
- Published
- 2025-05-26
- Volume
- 12
- Pages
- 1611842-1611842
- ISSN
- 2296-889X (ISSN-L)
- PMC
- PMC12146192
- OpenAlex
- W4410729041
- Cited by
- 51
- References
- 239
- Citations by year
- 2026: 42 · 2025: 9
- FWCI
- 6.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Molecular Biosciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fondo Nacional de Ciencia y Tecnología
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- oxidative stress, hypertension, diabetes mellitus, antioxidant therapy, reactive oxygen species, NADPH oxidase, mitochondrial dysfunction, endothelial dysfunction, vascular remodeling, hyperglycemia, beta-cell failure, insulin resistance, AGE-RAGE signaling pathway, polyol pathway, protein kinase C, F2-isoprostanes, 8-hydroxy-2'-deoxyguanosine, superoxide dismutase, glutathione peroxidase, Nrf2, gut microbiota, mitochondria-targeted antioxidants, NOX inhibitors, Mediterranean diet, physical activity, cardiometabolic dysfunction
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