Blood biomarkers for stroke: the role of thioredoxin in diagnosis and prognosis of acute ischemic stroke

Oraby, Mohammed I.; Rabie, Radwa A.

doi:10.1186/s41983-019-0122-7

Cited by 21 publications

(3 citation statements)

References 34 publications

(46 reference statements)

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“…Deregulation of the Trx system has been observed in various diseases including cancer [23], stroke [24], and cardiovascular diseases [25]. Overexpression of TrxR protein has been reported in many solid tumours, leading to increased TrxR activity that may contribute to tumour development through its growth-promoting capacities [10].…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic and radiosensitising effects of a novel thioredoxin reductase inhibitor in breast cancer

et al. 2021

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SummaryRadiotherapy is an effective treatment modality for breast cancer but, unfortunately, not all patients respond fully with a significant number experiencing local recurrences. Overexpression of thioredoxin and thioredoxin reductase has been reported to cause multidrug and radiation resistance - their inhibition may therefore improve therapeutic efficacy. Novel indolequinone compounds have been shown, in pancreatic cancer models, to inhibit thioredoxin reductase activity and exhibit potent anticancer activity. The present study evaluates, using in vitro breast cancer models, the efficacy of a novel indolequinone compound (IQ9) as a single agent and in combination with ionising radiation using a variety of endpoint assays including cell proliferation, clonogenic survival, enzyme activity, and western blotting. Three triple-negative breast cancer (MDA-MB-231, MDA-MB-468, and MDA-MB-436) and two luminal (MCF-7 and T47D) breast cancer cell lines were used. Results show that treatment with IQ9 significantly inhibited thioredoxin reductase activity, and inhibited cell growth and colony formation of breast cancer cells with IC50 values in the low micromolar ranges. Enhanced radiosensitivity of triple-negative breast cancer cells was observed, with sensitiser enhancement ratios of 1.20–1.43, but with no evident radiosensitisation of luminal breast cancer cell lines. IQ9 upregulated protein expression of thioredoxin reductase in luminal but not in triple-negative breast cancer cells which may explain the observed differential radiosensitisation. This study provides important evidence of the roles of the thioredoxin system as an exploitable radiobiological target in breast cancer cells and highlights the potential therapeutic value of indolequinones as radiosensitisers.***This study was not part of a clinical trial. Clinical trial registration number: N/A

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Section: Discussionmentioning

confidence: 99%

Cytotoxic and radiosensitising effects of a novel thioredoxin reductase inhibitor in breast cancer

et al. 2021

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“…The TRX protein can be used as a marker, with its increased levels indicative of oxidative stress. The upregulation of TRX is a protective response to counteract the damaging effects of oxidative stress [104,105].…”

Section: Secondary Enzymesmentioning

confidence: 99%

Oxidative Stress: Mechanisms, Quantification and its role in human aging

Krishnamurthy,

Pereira,

et al. 2024

Preprint

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Oxidative stress refers to the imbalance between the production of oxidant species and the body’s ability to quench them using antioxidants, favoring the rise in oxidant levels. This leads to the damage of cellular macromolecules such as lipids, DNA, RNA, and proteins. The body’s ability to manage oxidative stress and maintain it at an optimum level is crucial for overall health. Oxidative damage, if left unmitigated, contributes to the aging process characterized by the progressive deterioration of physiological functions and cellular structures. Understanding the mechanisms of oxidative stress along with its reliable quantification can enable consistency and comparability in clinical practice across diseases. While direct quantification of oxidant species in the body would be ideal for assessing oxidative stress, it is not feasible owing to their high reactivity, short half-life, and quantification challenges using conventional techniques. Quantifying oxidative damage products and antioxidants pose as appropriate markers, indicating the degree of oxidative stress in the body. This review comprehensively discusses the mechanism of generation of key oxidant species, their sources, the beneficial roles played by them at low levels and the detrimental effects exerted by their elevated levels. The review also provides insights into the effective quantification techniques for damage products of lipids nucleic acids, and proteins along with the endogenous and exogenous antioxidant markers. Effective quantification of oxidative stress may improve our understanding on the phenomenon which may aid in maintaining cellular integrity, preventing age-associated diseases, and thereby promoting optimal well-being and longevity.

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“…However, it is important to understand that the variance of redox biomarkers levels is seen in many diseases, which makes it difficult to associate one specific biomarker with acute ischemic stroke. Concurrently, the changes occurring in oxidative homeostasis can be carried out by qualitatively and quantitatively evaluating the biomarkers that enable the accessible disease prognosis [ 21 , 44 , 45 , 46 , 47 ]. The oxidative stress-associated tissue damage occurring in many pathologies is often appraised by determining the extent of the cellular pathways that compel the structural and functional impairment of molecules.…”

Section: Introductionmentioning

confidence: 99%

The Role of Potential Oxidative Biomarkers in the Prognosis of Acute Ischemic Stroke and the Exploration of Antioxidants as Possible Preventive and Treatment Options

Zahra

Lefter

Jaber

et al. 2023

IJMS

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Ischemic strokes occur when the blood supply to a part of the brain is interrupted or reduced due to arterial blockage, and it often leads to damage to brain cells or death. According to a myriad of experimental studies, oxidative stress is an important pathophysiological mechanism of ischemic stroke. In this narrative review, we aimed to identify how the alterations of oxidative stress biomarkers could suggest a severity-reflecting diagnosis of ischemic stroke and how these interactions may provide new molecular targets for neuroprotective therapies. We performed an eligibility criteria-based search on three main scientific databases. We found that patients with acute ischemic stroke are characterized by increased oxidative stress markers levels, such as the total antioxidant capacity, F2-isoprostanes, hydroxynonenal, total and perchloric acid oxygen radical absorbance capacity (ORACTOT and ORACPCA), malondialdehyde (MDA), myeloperoxidase, and urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine. Thus, acute ischemic stroke is causing significant oxidative stress and associated molecular and cellular damage. The assessment of these molecular markers could be useful in diagnosing ischemic stroke, finding its causes, predicting its severity and outcomes, reducing its impact on the cellular structures of the brain, and guiding preventive treatment towards antioxidant-based therapy as novel therapeutic alternatives.

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Blood biomarkers for stroke: the role of thioredoxin in diagnosis and prognosis of acute ischemic stroke

Cited by 21 publications

References 34 publications

Cytotoxic and radiosensitising effects of a novel thioredoxin reductase inhibitor in breast cancer

Cytotoxic and radiosensitising effects of a novel thioredoxin reductase inhibitor in breast cancer

Oxidative Stress: Mechanisms, Quantification and its role in human aging

The Role of Potential Oxidative Biomarkers in the Prognosis of Acute Ischemic Stroke and the Exploration of Antioxidants as Possible Preventive and Treatment Options

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