Formation of Reactive Oxygen Species by Spermatozoa From Asthenospermic Patients: Response to Treatment With Pentoxifylline

The development of nonhormonal treatment of pemphigus vulgaris (PV) has been hampered by a lack of clear understanding of the mechanisms leading to keratinocyte (KC) detachment and death in pemphigus. In this study, we sought to identify changes in the vital mitochondrial functions in KCs treated with the sera from PV patients and healthy donors. PV sera significantly increased proton leakage from KCs, suggesting that PV IgGs increase production of reactive oxygen species. Indeed, measurement of intracellular reactive oxygen species production showed a drastic increase of cell staining in response to treatment by PV sera, which was confirmed by FACS analysis. Exposure of KCs to PV sera also caused dramatic changes in the mitochondrial membrane potential detected with the JC-1 dye. These changes can trigger the mitochondria-mediated intrinsic apoptosis. Although sera from different PV patients elicited unique patterns of mitochondrial damage, the mitochondria-protecting drugs nicotinamide (also called niacinamide), minocycline, and cyclosporine A exhibited a uniform protective effect. Their therapeutic activity was validated in the passive transfer model of PV in neonatal BALB/c mice. The highest efficacy of mitochondrial protection of the combination of these drugs found in mitochondrial assay was consistent with the ability of the same drug combination to abolish acantholysis in mouse skin. These findings provide a theoretical background for clinical reports of the efficacy of mitochondria-protecting drugs in PV patients. Pharmacological protection of mitochondria and/or compensation of an altered mitochondrial function may therefore become a novel approach to development of personalized nonhormonal therapies of patients with this potentially lethal autoimmune blistering disease.

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Human Fibroblasts Release Reactive Oxygen Species in Response to Treatment with Synovial Fluids from Patients Suffering from Arthritis

Free Radical Research Communications ◽

10.3109/10715769009087988 ◽

1990 ◽

Vol 8 (3) ◽

pp. 149-160 ◽

Cited By ~ 36

Author(s):

Beate Meier ◽

Heinfried H. Radeke ◽

Susanne Selle ◽

H.-H. Raspe ◽

Helmut Sies ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Human Fibroblasts ◽

Reactive Oxygen ◽

Response To Treatment ◽

Oxygen Species ◽

Synovial Fluids

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Overexpression of Reactive Oxygen Species Modulator 1 Predicts Unfavorable Clinical Outcome in EGFR-Mutant Lung Adenocarcinomas Treated With Targeted Therapy

Frontiers in Oncology ◽

10.3389/fonc.2021.770230 ◽

2021 ◽

Vol 11 ◽

Author(s):

Won Gun Kwack ◽

Ji-Youn Sung ◽

Seung Hyeun Lee

Keyword(s):

Reactive Oxygen Species ◽

Kinase Inhibitors ◽

Multivariate Analyses ◽

Reactive Oxygen ◽

Progression Free Survival ◽

Poor Response ◽

Response To Treatment ◽

Oxygen Species ◽

T790m Mutation ◽

Distinct Subgroup

PurposeReactive oxygen species modulator 1 (Romo1) is a novel protein that regulates the production of intracellular reactive oxygen species. Romo1 has been shown to be associated with poor survival in various clinical settings for the treatment of lung cancer. In this study, we evaluated whether tissue Romo1 expression was associated with clinical outcomes in epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma treated with tyrosine kinase inhibitors (TKIs).MethodRomo1 expression in tumor tissues was examined by immunohistochemistry and evaluated by histologic score. Univariate and multivariate analyses were performed to identify the clinicopathologic parameters, including Romo1 expression, which may be associated with progression-free survival (PFS), overall survival (OS), and incidence of secondary T790M mutation.ResultsA total of 96 tumor specimens were analyzed. With the cut-off value of 200, 71 (74.0%) and 25 (26.0%) patients were classified into low and high Romo1 groups, respectively. The median PFS of the high Romo1 group was significantly shorter than that of the low Romo1 group (13.1 vs 19.9 months, p = 0.0165). The median OS of the high Romo1 group was also significantly shorter than that of the low Romo1 group (19.8 vs 37.0 months, p = 0.0006). Multivariate analyses showed that high Romo1 expression was independently associated with both poor PFS (hazard ratio [HR] = 2.48, 95% confidence interval [CI]: 1.35–4.56, p = 0.0034) and poor OS (HR = 3.17, 95% CI: 1.57–6.41, p = 0.0013). In addition, the rate of secondary T790M mutation after TKI failure was significantly lower in the high Romo1 group than the low Romo1 group (16.7% vs. 38.3%, p = 0.0369).ConclusionsRomo1 overexpression was associated with poor response to treatment and short survival in patients treated with EGFR-TKIs, suggesting a distinct subgroup warranting active surveillance and tailored therapeutic approach. In addition, our data highlight that Romo1 could be a potential predictive and prognostic biomarker for this patient population.

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Mitochondria as a source of reactive oxygen species

Biochemical Journal ◽

10.1042/bj20090056 ◽

2009 ◽

pp. c3 ◽

Cited By ~ 1

Author(s):

Helena M. Cochemé ◽

Michael P. Murphy

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Oxygen Species

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Clinical aspects of reactive oxygen and nitrogen species

Biochemical Society Symposium ◽

10.1042/bss0710121 ◽

2004 ◽

Vol 71 ◽

pp. 121-133 ◽

Cited By ~ 25

Author(s):

Ascan Warnholtz ◽

Maria Wendt ◽

Michael August ◽

Thomas Münzel

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Risk Factor ◽

Endothelial Dysfunction ◽

Vascular Tissue ◽

Rapid Development ◽

Reactive Oxygen ◽

Clinical Aspects ◽

No Production ◽

Oxygen Species

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus and chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species in endothelial and/or smooth muscle cells and the adventitia, and the subsequent decrease in vascular bioavailability of NO. Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include NAD(P)H-oxidase, xanthine oxidase and endothelial nitric oxide synthase in an uncoupled state. Recent studies indicate that endothelial dysfunction of peripheral and coronary resistance and conductance vessels represents a strong and independent risk factor for future cardiovascular events. Ways to reduce endothelial dysfunction include risk-factor modification and treatment with substances that have been shown to reduce oxidative stress and, simultaneously, to stimulate endothelial NO production, such as inhibitors of angiotensin-converting enzyme or the statins. In contrast, in conditions where increased production of reactive oxygen species, such as superoxide, in vascular tissue is established, treatment with NO, e.g. via administration of nitroglycerin, results in a rapid development of endothelial dysfunction, which may worsen the prognosis in patients with established coronary artery disease.

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