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Review
. 2024 Feb 23;12(3):501.
doi: 10.3390/biomedicines12030501.

Novel Multi-Antioxidant Approach for Ischemic Stroke Therapy Targeting the Role of Oxidative Stress

Camilo Briones-Valdivieso  1 , Felipe Briones  2 , Sofía Orellana-Urzúa  3 , Silvia Chichiarelli  4 , Luciano Saso  5 , Ramón Rodrigo  3
Affiliations
Review

Novel Multi-Antioxidant Approach for Ischemic Stroke Therapy Targeting the Role of Oxidative Stress

Camilo Briones-Valdivieso et al. Biomedicines. .

Abstract

Stroke is a major contributor to global mortality and disability. While reperfusion is essential for preventing neuronal death in the penumbra, it also triggers cerebral ischemia-reperfusion injury, a paradoxical injury primarily caused by oxidative stress, inflammation, and blood-brain barrier disruption. An oxidative burst inflicts marked cellular damage, ranging from alterations in mitochondrial function to lipid peroxidation and the activation of intricate signalling pathways that can even lead to cell death. Thus, given the pivotal role of oxidative stress in the mechanisms of cerebral ischemia-reperfusion injury, the reinforcement of the antioxidant defence system has been proposed as a protective approach. Although this strategy has proven to be successful in experimental models, its translation into clinical practice has yielded inconsistent results. However, it should be considered that the availability of numerous antioxidant molecules with a wide range of chemical properties can affect the extent of injury; several groups of antioxidant molecules, including polyphenols, carotenoids, and vitamins, among other antioxidant compounds, can mitigate this damage by intervening in multiple signalling pathways at various stages. Multiple clinical trials have previously been conducted to evaluate these properties using melatonin, acetyl-L-carnitine, chrysanthemum extract, edaravone dexborneol, saffron, coenzyme Q10, and oleoylethanolamide, among other treatments. Therefore, multi-antioxidant therapy emerges as a promising novel therapeutic option due to the potential synergistic effect provided by the simultaneous roles of the individual compounds.

Keywords: antioxidants; oxidative stress; stroke.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Summary of brain damage mechanisms. MMP: Matrix metalloproteinases. NO: Nitric oxide. VEGF: Vascular endothelial growth factor.
Figure 2
Figure 2
Pathways of cell damage and possible antioxidant target. NLRP3: Leucine-rich repeat protein 3; ROS: reactive oxygen species; JAK2: Janus kinase 2; STAT3: signal transducer and activator of transcription 3; PI3K: phosphoinositide 3-kinase; Akt: protein kinase B; mTOR: mammalian target of rapamycin; Bcl2: B-cell lymphoma 2; Bax: Bcl-2-associated X protein; Sirt1: silent information regulator 1; NF-κB: nuclear factor-kappa B; Nrf2: nuclear factor erythroid 2-related factor 2; TLR: Toll-like receptor; DHBAc: dihydroxybenzoic acid; KLF4: Krüppel-like factor 4; TRX1: thioredoxin 1; HO-1: heme oxygenase-1; NQO1: NAD(P)H quinone oxidoreductase 1; GPX4: glutathione peroxidase 4; GSH: glutathione; xCt: cystine/glutamate antiporter.
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