Increased systemic oxidative stress in patients with keratoconus

PurposeTo establish the effect of systemic oxidative stress on the pathogenesis of keratoconus by measuring serum total oxidant status (TOS) and total antioxidant status (TAS) in patients with keratoconus.MethodsTwenty-five patients with keratoconus (keratoconus group) and 25 age-sex-matched healthy subjects (control group) were enrolled in the study. Exclusion criteria were smoking habit, history of any other corneal pathology, systemic disease or inflammation, and current antioxidant or anti-inflammatory therapies. All participants underwent a detailed ophthalmological examination and corneal topography. Serum samples were obtained from all participants. Oxidative stress markers (TAS and TOS) were measured using a commercial kit and oxidative stress index (OSI) was calculated.ResultsThe study comprised 25 patients with keratoconus (mean age of 26.4±1.7 years) and 25 healthy control subjects (mean age of 26.6±1.7 years) (P>0.05). The serum TOS and OSI values were significantly higher in patients with keratoconus compared with those of the controls (P=0.036 and 0.037, respectively). However, serum TAS did not show significant difference between the keratoconus and control groups (P=0.497).ConclusionsThe higher levels of serum oxidant status and OSI in patients with keratoconus suggest that systemic oxidative stress might be involved in the pathogenesis of keratoconus. © 2014 Macmillan Publishers Limited

Nitric oxide synthetic pathway and cGMP levels are altered in red blood cells from end-stage renal disease patients

Red blood cells (RBCs) enzymatically produce nitric oxide (NO) by a functional RBC-nitric oxide synthase (RBC-NOS). NO is a vascular key regulatory molecule. In RBCs its generation is complex and influenced by several factors, including insulin, acetylcholine, and calcium. NO availability is reduced in end-stage renal disease (ESRD) and associated with endothelial dysfunction. We previously demonstrated that, through increased phosphatidylserine membrane exposure, ESRD-RBCs augmented their adhesion to human cultured endothelium, in which NO bioavailability decreased. Since RBC-NOS-dependent NO production in ESRD is unknown, this study aimed to investigate RBC-NOS levels/activation, NO production/bioavailability in RBCs from healthy control subjects (C, N = 18) and ESRD patients (N = 27). Although RBC-NOS expression was lower in ESRD-RBCs, NO, cyclic guanosine monophosphate (cGMP), RBC-NOS Serine1177 phosphorylation level and eNOS/Calmodulin (CaM)/Heat Shock Protein-90 (HSP90) interaction levels were higher in ESRD-RBCs, indicating increased enzyme activation. Conversely, following RBCs stimulation with insulin or ionomycin, NO and cGMP levels were significantly lower in ESRD- than in C-RBCs, suggesting that uremia might reduce the RBC-NOS response to further stimuli. Additionally, the activity of multidrug-resistance-associated protein-4 (MRP4; cGMP-membrane transporter) was significantly lower in ESRD-RBCs, suggesting a possible compromised efflux of cGMP across the ESRD-RBCs membrane. This study for the first time showed highest basal RBC-NOS activation in ESRD-RBCs, possibly to reduce the negative impact of decreased NOS expression. It is further conceivable that high NO production only partially affects cell function of ESRD-RBCs maybe because in vivo they are unable to respond to physiologic stimuli, such as calcium and/or insulin

Public Health Reports ; v. 46, no. 43 : table of contents

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Spontaneously Hypertensive Rats

https://stars.library.ucf.edu/cfm-ch-register-vol13/1230/thumbnail.jp

Effect of sulfite on red blood cell deformability ex vivo and in normal and sulfite oxidase-deficient rats in vivo.

The effect of sulfite, a widely used food additive, on red blood cell deformability ex vivo and in vivo was investigated. Ex vivo experiments were conducted in human blood exposed to sulfite (5, 10 and 20 mM). In vivo experiments were carried out in sulfite oxidase-competent (SOXC) and sulfite oxidase-deficient (SOXD) rats. In the in vivo experiments, sulfite was administered in the form of sodium metabisulfite (Na(2)S(2)O(5), 25 mg/kg/day) via drinking water. Vitamin E dissolved in olive oil at a dose of 50 mg/kg was administered by gastric gavages. Red blood cell (RBC) deformability was determined at various fluid shear stresses using an ektacytometer. Ex vivo sulfite exposure to RBC did not affect RBC deformability. In the in vivo experiments, although RBC deformability was not affected by sulfite treatment in SOXD rats, it was found to be significantly increased in SOXC rats. Vitamin E treatment in combination with sulfite caused impairment in RBC deformability in both SOXC and SOXD rats. We suggest that sulfite needs to be oxidized in order to improve RBC deformability

Effect of sulfite treatment on erythrocyte deformability in young and aged rats.

It is known that aging is associated with marked effects on integrity and function of cell membrane. These effects may also be exacerbated by exogenous chemicals, e.g. sulfite. Thus, the aim of this paper is to examine the influence of sulfite on hemorheological and related hematological parameters in rats of various ages. In this study, male Wistar rats at the age of 3 and 18 months were used and the following parameters were evaluated: Mean Cell Volume (MCV), Mean Corpuscular Hemoglobin Concentration (MCHC), Red blood Cell (RBC) deformability and aggregation. The results show that aging is associated with a decrease in RBC deformability and MCHC, an increase in MCV. Sulfite administration significantly increased RBC deformability in both young and aged rats. Although MCHC was decreased in young rats, it was increased in aged rats in response to sulfite exposure. Additionally, sulfite induced a decrement in MCV of aged rats. Neither aging nor sulfite treatment caused significant alterations in RBC aggregation parameters in all experimental groups. In conclusion, these findings suggest that RBC deformability impairs with age and sulfite has ameliorating effects on RBC deformability in both young and aged rats

Effect of ingested sulfite on hippocampus antioxidant enzyme activities in sulfite oxidase competent and deficient rats.

Animal tissues are exposed to sulfite used as a preservative in food and drugs, and generated from the catabolism of sulfur-containing amino acids. Sulfite, which is a very reactive and potentially toxic molecule, is detoxified by the enzyme sulfite oxidase (SOX). Laboratory animals can be made deficient in SOX by the administration of a high-tungsten/low molybdenum regimen. It has been suggested that SOX deficient rats might be used as a model for the prediction of sulfite toxicity in humans. The aim of this study was to investigate the effects of ingested sulfite on hippocampus superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities in SOX competent and deficient rats. Hippocampus SOD, CAT and GPx activities were found to be significantly increased by sulfite treatment in SOX competent groups. On the other hand, exposure to sulfite had no effect on antioxidant status in hippocampus of SOX deficient rats. In conclusion, these results suggest that hippocampus antioxidant capacity where defense mechanism against the oxidative challenge is up regulated by sulfite in SOX competent rats. This up regulation mechanism in antioxidant enzymes against to sulfite related oxidative stress is not observed in SOX deficient rats and remains to be explained

in sulfite oxidase competent and deficient rats

Animal tissues are exposed to sulfite used as a preservative in food and drugs, and generated from the catabolism of sulfur-containing amino acids. Sulfite, which is a very reactive and potentially toxic molecule, is detoxified by the enzyme sulfite oxidase (SOX). Laboratory animals can be made deficient in SOX by the administration of a high-tungsten/low molybdenum regimen. It has been suggested that SOX deficient rats might be used as a model for the prediction of sulfite toxicity in humans. The aim of this study was to investigate the effects of ingested sulfite on hippocampus superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities in SOX competent and deficient rats. Hippocampus SOD, CAT and GPx activities were found to be significantly increased by sulfite treatment in SOX competent groups. On the other hand, exposure to sulfite had no effect on antioxidant status in hippocampus of SOX deficient rats. In conclusion, these results suggest that hippocampus antioxidant capacity where defense mechanism against the oxidative challenge is up regulated by sulfite in SOX competent rats. This up regulation mechanism in antioxidant enzymes against to sulfite related oxidative stress is not observed in SOX deficient rats and remains to be explained.C1 Pamukkale Univ, Fac Med, Dept Physiol, TR-20020 Denizli, Turkey.Akdeniz Univ, Fac Med, Dept Physiol, Antalya, Turkey