Sodium–glucose co-transporter 2 inhibitors (iSGLT2) have been linked to a considerable reduction in cardiovascular risk in patients with type 2 diabetes (T2D), but the precise molecular mechanisms are still elusive. We aimed to evaluate the effects of the iSGLT2 empagliflozin on systemic inflammation and its potential antioxidant properties. This is an observational, prospective follow-up study of a cohort of fifteen patients with T2D who received 10 mg/day of empagliflozin according to standard clinical care. Measures at baseline, 12 and 24 weeks were taken. Metabolic and anthropometric parameters were evaluated. Production of mitochondrial superoxide, glutathione content, and glutathione s-reductase and catalase mRNA levels were measured in leukocytes. Serum levels of myeloperoxidase, hs-CRP and IL-10 were determined. In addition to decreased body weight and reduced glucose and HbA1c levels, we observed a reduction in superoxide production in leukocytes of diabetic patients and increased glutathione content, prominently after 24 weeks of empagliflozin treatment. Leukocyte expression of glutathione s-reductase and catalase, and serum levels of IL-10 were enhanced at 24 weeks of empagliflozin treatment. Concomitantly, reduced hs-CRP and myeloperoxidase levels were seen. This study provides evidence of the antioxidant and anti-inflammatory properties of empagliflozin treatment in humans, which may contribute to its beneficial cardiovascular effects.
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.
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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