Effects of Occupational Inorganic Dust Exposure on Plasma Glutathione

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Methodological Fallacies in the Determination of Serum/Plasma Glutathione Limit Its Translational Potential in Chronic Obstructive Pulmonary Disease

This study aimed to review and critically appraise the current methodological issues undermining the suitability of the measurement of serum/plasma glutathione, both in the total and reduced form, as a measure of systemic oxidative stress in chronic obstructive pulmonary disease (COPD). Fourteen relevant articles published between 2001 and 2020, in 2003 subjects, 1111 COPD patients, and 892 controls, were reviewed. Nine studies, in 902 COPD patients and 660 controls, measured glutathione (GSH) in the reduced form (rGSH), while the remaining five, in 209 COPD patients and 232 controls, measured total GSH (tGSH). In the control group, tGSH ranged between 5.7 and 7.5 µmol/L, whilst in COPD patients, it ranged between 4.5 and 7.4 µmol/L. The mean tGSH was 6.6 ± 0.9 µmol/L in controls and 5.9 ± 1.4 µmol/L in patients. The concentrations of rGSH in the control group showed a wide range, between 0.47 and 415 µmol/L, and a mean value of 71.9 ± 143.1 µmol/L. Similarly, the concentrations of rGSH in COPD patients ranged between 0.49 and 279 µmol/L, with a mean value of 49.9 ± 95.9 µmol/L. Pooled tGSH concentrations were not significantly different between patients and controls (standard mean difference (SMD) = −1.92, 95% CI −1582 to 0.0219; p = 0.057). Depending on whether the mean concentrations of rGSH in controls were within the accepted normal range of 0.5–5.0 µmol/L, pooled rGSH concentrations showed either a significant (SMD = −3.8, 95% CI −2.266 to −0.709; p < 0.0001) or nonsignificant (SMD = −0.712, 95% CI −0.627 to 0.293; p = 0.48) difference. These results illustrate the existing and largely unaddressed methodological issues in the interpretation of the serum/plasma concentrations of tGSH and rGSH in COPD.

Plasma glutathione status as indicator of pre-analytical centrifugation delay

Prolonged incubation of blood prior to plasma preparation can significantly influence the quality of the resulting data. Different markers for this pre-clinical variability have been proposed over the years but with limited success. In this study we explored the usefulness of glutathione (GSH) status, namely ratio of reduced to oxidized glutathione (GSH/GSSG), as potential marker of plasma preparation delay. For that purpose, blood from 20 healthy volunteers was collected into tubes with a cysteine quencher (N-ethylmaleimide; NEM) for GSH stabilization. Plasma preparation was delayed at room temperature for up to 3 hours and every hour, a plasma sample was prepared and the GSH/GSSG ratio measured. We report that over the course of the investigation, plasma concentrations of both GSH and GSSG increased linearly (R2 = 0.99 and 0.98, respectively). Since GSH increased at a much faster rate compared to GSSG, the GSH/GSSG ratio also increased linearly in a time dependent manner (R2 = 0.99). As GSH is an intracellular antioxidant, we speculated that this might stem from ongoing blood hemolysis, which was confirmed by the time dependent rise in lactate dehydrogenase (LDH) activity in the plasma samples. Moreover, we demonstrate that the addition of the thiol alkylating reagent NEM directly to the blood tubes does not seem to influence downstream analysis of clinical parameters. In conclusion we propose that the glutathione status could be used as an indicator of the centrifugation delay prior to plasma preparation.

Metabolomic Analysis Identified Reduced Levels of Xenobiotics, Oxidative Stress, and Improved Vitamin Metabolism in Smokers Switched to Vuse Electronic Nicotine Delivery System

Introduction Switching to noncombustible tobacco products presents an opportunity for cigarette smokers to potentially reduce the health risks associated with smoking. Electronic Nicotine Delivery Systems (ENDS) are one such product because the vapor produced from ENDS contains far fewer toxicants than cigarette smoke. To investigate the biochemical effects of switching from smoking to an ENDS, we assessed global metabolomic profiles of smokers in a 7-day confinement clinical study. Methods In the first 2 days of this clinical study, the subjects used their usual brand of cigarettes and then switched to exclusive ENDS ad libitum use for 5 days. Urine and plasma samples were collected at baseline and 5 days after switching. The samples were analyzed using a mass spectrometry-based metabolomic platform. Results Random forest analyses of urine and plasma metabolomic data revealed excellent predictive accuracy (&gt;97%) of a 30-metabolite signature that can differentiate smokers from 5-day ENDS switchers. In these signatures, most biomarkers are nicotine-derived metabolites or xenobiotics. They were significantly reduced in urine and plasma, suggesting a decreased xenobiotic load on subjects. Our results also show significantly decreased levels of plasma glutathione metabolites after switching, which suggests reduced levels of oxidative stress. In addition, increased urinary and plasma levels of vitamins and antioxidants were identified, suggesting enhanced bioavailability due to discontinuation of cigarette smoking and switching to Vuse ENDS use. Conclusions Our results suggest reduced toxicant exposure, reduced oxidative stress, and potential beneficial changes in vitamin metabolism within 5 days in smokers switching to Vuse ENDS. Implications Switching from smoking to exclusive ENDS use in clinical confinement settings results in significant reduction of nicotine metabolites and other cigarette-related xenobiotics in urine and plasma of subjects. Significantly decreased oxidative stress-related metabolites and increased urinary and plasma levels of vitamin metabolites and antioxidants in 5-day short-term ENDS switchers suggest less toxic physiological environment for consumers of ENDS products and potential health benefits if such changes persist.

Supplementation of Postbiotic RI11 Improves Antioxidant Enzymes Activity, Upregulated Gut Barrier Genes and Reduced Cytokines, Acute Phase Proteins and HSP70 Gene Expression Levels in Heat-Stressed Broilers

Background To alleviate the adverse impacts of stressful environmental conditions on poultry and promoting the animal's health and growth performance, antibiotics have been added to poultry diets as growth promoters. Nevertheless, improper and overuse of antibiotics as feed additives have resulted the emergence of antibiotic-resistant bacteria and increased the levels of antibiotic residues in animal products, which have disastrous effects on the health of both animals and humans. Postbiotics produced from probiotic Lactobacillus plantarum have been the recent research of interest as dietary additives for livestock and potential alternatives to antibiotics. However, there is very scarce of study has considered the effect of postbiotics on broilers under heat stress. The aim of this work was to evaluate the impacts of feeding different levels of postbiotic RI11 on antioxidant enzyme activity, physiological stress indicators, cytokines and gut barrier genes expression in broilers under heat stress. Materials and Methods A total of 252 male Cobb 500 were fed with 1 of 7 diets: NC (negative control, 0.0% RI11) basal diet; OTC (positive control) NC + 0.02% (w/w) oxytetracycline; AA (antioxidant control) NC + 0.02% (w/w) ascorbic acid. Four further groups were NC + 0.2, 0.4, 0.6 and 0.8% postbiotic RI11 (v/w) of the respective levels. Results Supplementation of different levels of postbiotic RI11 increased plasma glutathione peroxidase, catalase and glutathione enzymes activity. Postbiotic RI11 groups upregulated the mRNA expression of interleukin 10 and downregulated of interleukin 8, tumor necrosis factor-alpha, heat shock protein 70 and alpha 1- acid glycoprotein levels compared to the NC and OTC groups. Feeding various doges of postbiotic RI11 improved the integrity of the intestinal barrier by the upregulation of zonula occludens-1 and mucin2 mRNA expressions. However, no difference was observed in claudin1, ceruloplasmin, interleukin 6, interleukin 2 and interferon expression, but downregulation for occludin expression as compared with the NC group. Supplementation of postbiotic RI11 in different levels quadratically increased the plasma glutathione peroxidase, catalase and glutathione, interleukin 10, mucin2 and zonula occludens-1 mRNA expression, and reduced plasma interleukin 8, tumor necrosis factor-alpha, alpha 1- acid glycoprotein and heat shock protein 70 mRNA expression. Supplementation of postbiotic RI11 at level 0.6% was sufficient to achieve the improvement in health of broiler chickens under heat stress as compared to other levels. Conclusions The results suggested that postbiotic produced from L. plantarum RI11 particularly at level 0.6% (v/w) could be used as an alternative to antibiotics and natural sources of antioxidants in the poultry industry.

Clinical Prognosis for SAH Consistent with Redox Imbalance and Lipid Peroxidation

Subarachnoid hemorrhage (SAH) accounts for 3% of all strokes. As more and more data indicates the role of oxidative stress in acute brain damage caused by SAH, an attempt was made to correlate the clinical status of patients with systemic level of antioxidants and lipid peroxidation products. The hemorrhage was diagnosed with brain computed tomography (CT) and aneurysm with angio-CT and angiography, while the vasospasm was monitored with transcranial Doppler. Plasma glutathione peroxidase activity (GSH-Px) and vitamin A, E, and C levels were determined spectrophotometrically and by HPLC, respectively. The levels of polyunsaturated fatty acids (PUFAs) cyclization products were determined by GC–MS, while F2-isoprostanes and neuroprostanes (NP) were determined by LC–MS. SAH was accompanied by changes in antioxidant capacity in blood plasma, including initially (day 1) an increase in GSH-Px activity, followed by its decrease and a progressive decrease in glutathione (GSH) levels and vitamins A, E, and C. On the other hand, levels of PUFAs cyclization products, F2-isoprostanes, and neuroprostanes were highest on day 1 (two and eight times higher, respectively) and decreased over time. The levels of 4-HNE (4-hydroxynonenal), 4-ONE (4-oxononenal), and MDA (malondialdehyde) changed similarly. In contrast, the 4-HHE (4-hydroxyhexenal) level reduced after SAH increased significantly after a week. It was found that the deterioration of the overall clinical and neurological condition of SAH patients due to cerebral edema, intracranial hemorrhage, or vasoconstriction corresponded to reduced antioxidant defense and, as a consequence, increased lipid peroxidation and slower observed changes in regression. It can be concluded that monitoring the level of lipid peroxidation products (neuroprostanes, 4-ONE, and MDA) can support the monitoring of the clinical status of patients, especially with regard to the assessment of vasospasm.

Correlation Between Age, Body Mass Index, And Blood Selenium Level with Glutathione Peroxidase Activity Among Elderly in South Jakarta

Oxidative stress contributed in aging process and several degenerative diseases. Selenium was an important trace element due to as a component of antioxidants enzymes (selenoproteins), including glutathione peroxidase for protection against free radical.Objective: We aimed to study the correlation between blood selenium level and plasma glutathione peroxidase activity in elderly.Materials and Methods: Cross sectional study was held in 5 elderly communities in south Jakarta. Body mass index, blood selenium level and plasma glutathione peroxidase activity were measured in 95 elderly aged between 60-86 years old. Nonparametric correlation was used for correlation analysis.Results and Discussion: The median of subject’s age was 69 years old (60-86) and for body mass index was 23.57 (13.59-36.05). The median of selenium level among subject was 0.19 (0.023-0.56). The mean of plasma glutathione peroxidase activity was 164.45 U/L ± 68.07. There was no correlation among variables. However, plasma glutathione peroxidase activity decreased with increasing age and body mass index although it was not significant.Conclusion: There was no correlation between blood selenium level and plasma glutathione peroxidase activity. Detection of plasma selenium level is needed to confirm this result.International Journal of Human and Health Sciences Vol. 04 No. 02 April’20 Page : 89-93

Plasma glutathione peroxidase (GPx3) activity in the freshwater turtle Trachemys scripta elegans after isoflurane inhalation anesthesia

Introduction. Glutathione peroxidases are selenoenzymes which have a crucial role in the protection of animals against oxidative stress. Materials and Methods. From September 2017 to April 2018, a group of eight red-eared sliders were admitted at the Clinic for Small Animals, Faculty of Veterinary Medicine, University of Belgrade for elective diagnostic celioscopy. The turtles were of unknown age, weight from 1.20 kg to 1.86 kg. The anesthesia protocol involved using ketamine and medetomidine, both at a low dosage (10 mg kg-1 and 0.1 mg kg-1, respectively) as induction, after which anesthesia was maintained using isoflurane at 3% (vapor setting) in 100% oxygen (0.5 L min-1). Medetomidine was reversed with atipamezole (0.2 mg kg-1), given intramuscularly. The elective celioscopy was performed according to standard protocols. One day prior to anesthesia, heparinized blood samples were taken using the subcarapacial venous plexus for venipuncture. The second sampling took place three hours after the anesthetics were administered. Results and Conclusions. GPx3 activity in the blood plasmas (n=8) was measured by the coupled test as described by G?nzler et al. (1974). Data were tested for normality by the Shapiro-Wilk normality test and the groups were compared using a paired t-test. Blood plasma GPx3 activity was significantly higher (p=0.009) after a three-hour recovery period from inhalation anesthesia performed for elective diagnostic celioscopy, than before anesthesia. The measured post-anesthesia GPx3 activities were, on average, 80% higher than the measurements prior to anesthesia. It can be concluded that the statistically significant increase in the activity of plasma GPx3 from 91.02?36.05 mKat L-1 prior to anesthesia to 160.21?58.94 mKat L-1 three hours after anesthesia is due to the change in oxygen saturation. This is increased to 100% during the procedure, thus exposing the turtles to conditions of high oxygen saturation.

Protective effect of coenzyme Q10 against bisphenol-A-induced toxicity in the rat testes

The present study was conducted to investigate the antioxidant, histomorphometric, histochemical, immunohistochemical, biochemical, and cytological effects of coenzyme Q10 (CoQ10) against bisphenol-A (BPA)-induced testicular toxicity in rats. A total of 40 adult male Wistar rats were divided into five equal groups. The control group remained untreated. The vehicle control group was administered corn oil (2 ml/kg/day), the BPA group was given BPA (100 mg/kg/day), the CoQ10 group was supplemented with CoQ10 (10 mg/kg/day), and the rats in the CoQ10-BPA group received CoQ10 (10 mg/kg/day) followed by BPA (100 mg/kg/day) 1 h later. The treatments were administered by oral gavage for 14 days. Results showed that the seminiferous tubule diameters (STDs) and seminiferous epithelium heights (SEHs) at stages VII–VIII and XII–XIV, number of undifferentiated embryonic cell transcription factor-1 (UTF-1) positive cells per tubule, UTF-1 positive tubules (%), plasma glutathione (GSH), and serum superoxide dismutase activities, testicular GSH activity and sperm viability (%) decreased whereas the number of terminal dUTP nick end labeling (TUNEL) positive cells per tubule, TUNEL positive tubules (%), testicular and serum malondialdehyde (MDA) levels, and the rate of mid-piece sperm abnormality increased in the BPA administered group. However, while the STDs at stages VII–VIII and XII–XIV, SEHs at stages VII–VIII, plasma GSH, and serum SOD activities increased, serum MDA level decreased in the CoQ10-BPA group. In conclusion, these results suggest a protective effect of CoQ10 against BPA-induced testicular toxicity in rats.