Targeting oxidative stress in disease: promise and limitations of antioxidant therapy

Forman, Henry Jay; Zhang, Hongqiao

doi:10.1038/s41573-021-00233-1

Cited by 1,370 publications

(1,041 citation statements)

References 291 publications

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“…Prior studies have shown that endothelial dysfunction acts in the preclinical development of atherosclerosis, and inflammation could increase the vulnerability of plaques. Under oxidative stress, LDL could be transformed into oxidized low-density lipoprotein (ox-LDL), and vascular endothelial dysfunction and increased permeability could promote the deposition of ox-LDL in the intima (33). Furthermore, the accumulated ox-LDL contributes to the initiation of inflammatory reactions, infiltration of monocytes and T cells, and accumulation of extracellular matrix (34).…”

Section: Discussionmentioning

confidence: 99%

Serum Bilirubin Levels and Extent of Symptomatic Intracranial Atherosclerotic Stenosis in Acute Ischemic Stroke: A Cross-Sectional Study

Zhou

Liao

et al. 2021

Front. Neurol.

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Background: Bilirubin plays a paradoxical role in the pathological mechanism of stroke. To date, few clinical studies have investigated the effect of serum bilirubin on symptomatic intracranial atherosclerotic stenosis (sICAS). This study aims to evaluate the connection between serum bilirubin and sICAS.Methods: From September 2015 to May 2020, 1,156 sICAS patients without hepatobiliary diseases admitted to our hospital were included. Patients were distributed into none-mild (0–49%), moderate (50–69%) and severe-occlusion sICAS groups (70–100%) by the degree of artery stenosis. Moderate and severe-occlusion sICAS patients were classified into three groups by the number of stenotic arteries (single-, two- and multiple-vessel stenosis). The relationship between serum bilirubin levels and sICAS was analyzed by logistic regression analysis.Results: In univariable analyses, sICAS patients with severe and multiple atherosclerotic stenoses had lower levels of total bilirubin (Tbil), direct bilirubin (Dbil), and indirect bilirubin (Ibil). In multinomial logistic regression analyses, when compared with the highest tertile of bilirubin, lower levels of Tbil, Dbil, and Ibil showed higher risks of severe-occlusion sICAS (95% CI: 2.018–6.075 in tertile 1 for Tbil; 2.380–7.410 in tertile 1 for Dbil; 1.758–5.641 in tertile 1 for Ibil). Moreover, the logistic regression analyses showed that lower levels of Tbil, Dbil, and Ibil were related to multiple (≥3) atherosclerotic stenoses (95% CI: 2.365–5.298 in tertile 1 and 2.312–5.208 in tertile 2 for Tbil; 1.743–3.835 in tertile 1 and 1.416–3.144 in tertile 2 for Dbil; 2.361–5.345 in tertile 1 and 1.604–3.545 in tertile 2 for Ibil) when compared with tertile 3.Conclusions: Our findings suggest that lower bilirubin levels may indicate severe and multiple intracranial atherosclerotic stenoses.

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Section: Discussionmentioning

confidence: 99%

Serum Bilirubin Levels and Extent of Symptomatic Intracranial Atherosclerotic Stenosis in Acute Ischemic Stroke: A Cross-Sectional Study

Zhou

Liao

et al. 2021

Front. Neurol.

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“…Oxidative stress induced by excessive ROS accumulation causes severe damage to cellular lipids, DNA, and proteins, linked to cancers, inflammatory, cardiovascular, and neurological diseases [ 33 , 34 , 35 ]. LPS activation of macrophages results in the formation of ROS.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Anti-Inflammatory and Antioxidant Effects of Citrus unshiu Peel (CUP) Flavonoids on LPS-Stimulated RAW 264.7 Cells

Karthikeyan

Kim

Vetrivel

et al. 2021

Plants

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Citrus unshiu is a popular medicinal herb in several Asian countries, in particular South Korea. C. unshiu peel (CUP) has several biologically active compounds, including flavonoids. Hence, this research aimed to label the flavonoids from CUP by HPLC-MS/MS analysis and examine their anti-inflammatory and antioxidant potential on LPS-stimulated RAW 264.7 macrophages. A total of four flavonoids (Rutin, naringin, hesperidin, and poncirin) were characterized, and their contents were quantified from CUP. It showed that the naringin is rich in CUP. Further, treatment with the flavonoids at concentrations of 2.5 and 5 μg/mL had no effect on the cell viability of RAW 264.7 macrophages. On the other hand, it decreased the production and expression of inflammatory mediators and pro-inflammatory cytokines such as NO, PGE2, TNF-α, IL-1β, iNOS, and COX2 in the LPS-stimulated RAW 264.7 macrophages. In addition, flavonoids treatment inhibited the NF-κB activation by downregulating the p-p65 and p-IκBα proteins expression. Furthermore, reactive oxygen species (ROS) production considerably decreased at the same concentrations while antioxidant enzyme activity increased in the LPS-stimulated RAW 264.7 macrophages. Collectively, our results show that CUP flavonoids have the potential to decrease inflammation and oxidative damage.

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“…Developing multiparametric state and process speci c redox signatures could have far-reaching signi cance. For example, disease speci c redox state signatures could rapidly screen how large numbers of patients respond to a treatment; which might make it easier to evaluate the therapeutic value of next-generation antioxidants 38 .…”

Section: Discussionmentioning

confidence: 99%

RedoxiFluor: A microplate assay to quantify protein thiol redox state in percentages and moles

Tuncay¹,

Noble

Guille

et al. 2021

Preprint

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An accessible, time- and cost-efficient microplate assay to quantify protein thiol redox state in percentages and moles relative to the thiol proteome (i.e., context) and other targets (i.e., array mode) would be invaluable for understanding how protein thiols regulate essential biological processes. RedoxiFluor achieves several key benefits (i.e., percentages, moles, context, array mode) in a microplate format. After robustly validating RedoxiFluor, comparative analysis reveals that key benefits are intractable to other immunological techniques. Moles is an unprecedented achievement. Proof-of-concept studies illuminating fundamental redox principles (i.e., specificity, context, and heterogeneity) through measurement alone demonstrate how RedoxiFluor can advance understanding. For example, target specific protein thiol redox state changes are: (1) context specific (i.e., redox stimulus dependent); (2) selective (i.e., redox stimuli oxidise select targets); and (3) heterogenous (i.e., target responses vary markedly). RedoxiFluor is a powerful new tool for advancing a far-reaching and influential field: protein thiol redox biology.

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Targeting oxidative stress in disease: promise and limitations of antioxidant therapy

Cited by 1,370 publications

References 291 publications

Serum Bilirubin Levels and Extent of Symptomatic Intracranial Atherosclerotic Stenosis in Acute Ischemic Stroke: A Cross-Sectional Study

Serum Bilirubin Levels and Extent of Symptomatic Intracranial Atherosclerotic Stenosis in Acute Ischemic Stroke: A Cross-Sectional Study

Assessment of Anti-Inflammatory and Antioxidant Effects of Citrus unshiu Peel (CUP) Flavonoids on LPS-Stimulated RAW 264.7 Cells

RedoxiFluor: A microplate assay to quantify protein thiol redox state in percentages and moles

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