Induction of Oxidative Stress and Human Leukocyte/Endothelial Cell Interactions in Polycystic Ovary Syndrome Patients with Insulin Resistance

Víctor, Víctor M.; Rocha, Milagros; Bañuls, Celia; Álvarez, Ángeles; Pablo, Carmen de; Sánchez-Serrano, María; Gómez, Mercedes; Hernández‐Mijares, Antonio

doi:10.1210/jc.2011-0651

Cited by 114 publications

(94 citation statements)

References 40 publications

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“…The parallel plate flow chamber in vitro model has been described in detail elsewhere (7). To perform adhesion assays, coverslips containing confluent HUVEC monolayers were inserted into a circular recess in the bottom plate of the flow chamber (maintained at 37°C), to which a 5 · 25 mm portion of the endothelial cells were exposed.…”

Section: Adhesion Assay Levels Of Cytokines and Adhesion Moleculesmentioning

confidence: 99%

Is Myeloperoxidase a Key Component in the ROS-Induced Vascular Damage Related to Nephropathy in Type 2 Diabetes?

Rovira‐Llopis

Rocha

Falcón

et al. 2013

Antioxidants & Redox Signaling

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It is still unclear whether microvascular complications of type 2 diabetes correlate with leukocyte-endothelium interactions and/or myeloperoxidase (MPO) levels. In the present study, we found that serum levels of glucose, the rate of ROS and MPO concentration were higher in type 2 diabetic patients. Patients with nephropathy (39.6%) presented higher MPO levels that correlate positively with the albumin/creatinine ratio (r = 0.59, p < 0.05). In addition, nephropatic patients showed increased leukocyte-endothelium interactions due to an undermining of polymorphonuclear leukocytes (PMN) rolling velocity and increased rolling flux and adhesion, which was accompanied by a rise in levels of the proinflammatory cytokine tumour necrosis factor alpha (TNFa) and the adhesion molecule E-selectin. Furthermore, MPO levels were positively correlated with PMN rolling flux (r = 0.855, p < 0.01) and adhesion (r = 0.682, p < 0.05). Our results lead to the hypothesis that type 2 diabetes induces oxidative stress and an increase in MPO levels and leukocyte-endothelium interactions, and that these effects correlate with the development of nephropathy.

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Section: Adhesion Assay Levels Of Cytokines and Adhesion Moleculesmentioning

confidence: 99%

Is Myeloperoxidase a Key Component in the ROS-Induced Vascular Damage Related to Nephropathy in Type 2 Diabetes?

Rovira‐Llopis

Rocha

Falcón

et al. 2013

Antioxidants & Redox Signaling

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“…3 The mechanism underlying oxidative stress in PCOS is not fully understood, but studies strongly suggest that insulin resistance plays a pivotal role in the pathogenesis of PCOS and encourages oxidative stress. 4 Oxidative stress (OS) is caused by imbalance between pro-oxidant and antioxidants. 5 This ratio can be altered by increased levels of reactive oxygen species (ROS) and /or reactive nitrogen species (RNS), or decrease in antioxidant defence mechanism.…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress and outcome of antioxidant supplementation in patients with polycystic ovarian syndrome (PCOS)

Panti

Shehu

Saidu

et al. 2018

Int J Reprod Contracept Obstet Gynecol

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Background: PCOS is a condition with significant decrease in antioxidant with an increased risk of oxidative stress. Antioxidant supplementation has been shown to improve insulin sensitivity in PCOS and may improve outcome of management of PCOS. Objectives of this study were to determine the oxidative stress level of PCOS patients, to assess the effect of antioxidant supplementation on the outcome of management of PCOS and to compare with a control group.Methods: The study was a single blind randomised control trial involving 200 patients with PCOS. The study was conducted at Usmanu Danfodiyo University Teaching Hospital Sokoto. They were randomly divided into intervention and control groups and base line serum levels of oxidative stress marker, antioxidant enzymes, vitamins and minerals were determined. Antioxidant supplementation and placebo were given to the intervention and control groups respectively. All the patients had ovulation induction with clomiphene citrate and were followed up for 6 months. Outcome measures were clinical pregnancy or menstrual regularisation. Level of significance was <0.05.Results: There was statistical significance in the serum levels of oxidative stress marker, antioxidant enzymes, vitamins and minerals between the two groups (post intervention). Glutathione peroxidase (p = 0.001), superoxide dismutase (p = 0.0001), catalase (p= 0.0369), melondialdehyde (p= 0.007), Vitamin A, Vitamin C, Vitamin E (p = 0.0001), zinc and copper (p = 0.0001). The clinical pregnancy outcomes were 22 (22%) versus 2 (2%); live births 18 (18%) versus 2 (2%) and menstrual regularisation 48 (48%) versus 46 (46%) in the intervention and control groups respectively.Conclusions: Antioxidant supplementation in this study significantly affected pregnancy rate in patients with PCOS. Larger studies are suggested to revisit the conclusion of the Cochrane review that antioxidants supplementation had no significant role in female infertility.

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“…Several studies in PCOS patients have demonstrated that acute hyperglycemia and IR induce an increase in reactive oxygen species (ROS) production by peripheral blood leukocytes (18,19), activate leukocyte-endothelium interactions (20) and proinflammatory transcription factor nuclear kappa B (NF-kB) (21), and increase levels of proinflammatory cytokines (22). In this way, oxidative stress has been implicated in the etiology of IR in leukocytes from PCOS patients.…”

Section: Introductionmentioning

confidence: 99%

Effects of metformin on mitochondrial function of leukocytes from polycystic ovary syndrome patients with insulin resistance

Víctor

Rovira‐Llopis

Bañuls

et al. 2015

European Journal of Endocrinology

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Objective: Oxidative stress and mitochondrial dysfunction are implicated in polycystic ovary syndrome (PCOS). The present study assesses the effect of metformin treatment on mitochondrial function in polymorphonuclear cells from PCOS subjects. Additionally, we evaluate endocrine parameters and levels of interleukin 6 (IL6) and tumour necrosis factor alpha (TNFa). Design and methods: Our study population was comprised of 35 women of reproductive age diagnosed with PCOS and treated with metformin for 12 weeks, and their corresponding controls (nZ41), adjusted by age and BMI. We evaluated the alteration of endocrinological and anthropometrical parameters and androgen levels. Mitochondrial O 2 consumption (using a Clark-type O 2 electrode), membrane potential, mitochondrial mass, and levels of reactive oxygen species (ROS) and glutathione (GSH) (by means of fluorescence microscopy) were assessed in poymorphonuclear cells. H 2 O 2 was evaluated with the Amplex Red R H 2 O 2 /Peroxidase Assay kit. IL6 and TNFa were measured using the Luminex 200 flow analyser system.Results: Metformin had beneficial effects on patients by increasing mitochondrial O 2 consumption, membrane potential, mitochondrial mass and glutathione levels, and by decreasing levels of reactive oxygen species and H 2 O 2 . In addition, metformin reduced glucose, follicle-stimulating hormone, IL6 and TNFa levels and increased dehydroepiandrosterone sulfate levels. HOMA-IR and mitochondrial function biomarkers positively correlated with ROS production (rZ0.486, PZ0.025), GSH content (rZ0.710, PZ0.049) and H 2 O 2 (rZ0.837, PZ0.010), and negatively correlated with membrane potential (rZK0.829, PZ0.011) at baseline. These differences disappeared after metformin treatment.Conclusions: Our results demonstrate the beneficial effects of metformin treatment on mitochondrial function in leukocytes of PCOS patients.

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Induction of Oxidative Stress and Human Leukocyte/Endothelial Cell Interactions in Polycystic Ovary Syndrome Patients with Insulin Resistance

Cited by 114 publications

References 40 publications

Is Myeloperoxidase a Key Component in the ROS-Induced Vascular Damage Related to Nephropathy in Type 2 Diabetes?

Is Myeloperoxidase a Key Component in the ROS-Induced Vascular Damage Related to Nephropathy in Type 2 Diabetes?

Oxidative stress and outcome of antioxidant supplementation in patients with polycystic ovarian syndrome (PCOS)

Effects of metformin on mitochondrial function of leukocytes from polycystic ovary syndrome patients with insulin resistance

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