Commiphora myrrh Supplementation Protects and Cures Ethanol-Induced Oxidative Alterations of Gastric Ulceration in Rats

Gastric ulceration is a multifactorial disease defined as a defect in the gastric wall that extends through the muscularis mucosae into the deeper layers of the wall. The most common cause of gastric ulceration is alcohol consumption. In the current study, rats were gavaged by ethanol to investigate the protective (before ethanol) and curative (after ethanol) ability of Commiphora myrrh (myrrh) oil and extract against gastric ulcer oxidative alterations induced by ethanol. Myrrh significantly improved ulcer index, histomorphology, and periodic acid Schiff (PAS) impaired by ethanol. In addition, myrrh improved the antioxidant potential of gastric mucosa through enhancement of nuclear factor related to erythroid 2 (Nrf2), total glutathione (GSH), reduced GSH, and oxidized glutathione (GSSG), along with significant reduction in malondialdehyde (MDA) levels. Amelioration of gastric oxidative stress by myrrh enables gastric mucosa to counteract the ethanol’s inflammatory and apoptotic processes leading to improved gastric proliferation and healing. Interestingly, myrrh extract showed better protective and curative effects than myrrh oil against gastric ulceration.

Profiling the Concentration of Reduced and Oxidized Glutathione in Rat Brain Using HPLC/DAD Chromatographic System

This study aimed to develop a HPLC/DAD method in order to determine and quantify the reduced glutathione (GSH) and oxidized glutathione (GSSG) levels in rat brain. Due to the presence of the thiol group (-SH), GSH can interact with the Ellman's reagent (DTNB), with which it forms a reaction product through which the level of GSH can be quantified, using the DAD detection system. Chromatographic separation was achieved after a derivatization process by using a mobile phase acetonitrile (A) and phosphate buffer (20 mM, pH = 2.5) (B). The compounds of interest were detected at 330 nm using a chromatographic C8 column. The method of determination met the validation criteria, specified by the regulatory bodies. The applicability of the method was demonstrated in a chronic toxicology study of central nervous system (CNS), following different treatment regimens with haloperidol.

Glutathione system activity in the blood of overweight postmenopausal women

One of the important components of the antioxidant defense system is the glutathione system, the activity of which, when overweight, changes direction depending on gender and ethnicity. The results of studies involving overweight menopausal women are mixed. The study involved 61 postmenopausal women, who, after clinical and anamnestic examination, were divided into 2 groups: control (BMI = 19-24.9 kg / m2) and overweight group (BMI = 25-29.9 kg/m2). The use of hormone replacement therapy; the use of antioxidant drugs; diseases of endocrine genesis; exacerbation of chronic diseases; premature early menopause; surgical menopause was the exclusion criteria for women from the study. The lipid profile parameters with the calculation of the atherogenic coefficient; reduced and oxidized glutathione levels with the calculation of their ratio, the glutathione S-transferase and glutathione reductase activities were determined in the blood. Overweight women showed an increase in the triacylglycerols (p = 0.041) and cholesterol in very low density lipoproteins levels (p = 0.044). When assessing the glutathione system activity in women of the main group, compared with the control, an increase in the glutathione-S-transferase (p = 0.023) and glutathione reductase (p = 0.022) activities was noted, however, the reduced and oxidized glutathione levels, as well as their ratio did not differ from the control values. The results obtained indicate the activation of the glutathione system enzymatic link in response to changes in lipid status in postmenopausal women with overweight.

A connexin/ifi30 pathway bridges HSCs with their niche to dampen oxidative stress

Reactive oxygen species (ROS) represent a by-product of metabolism and their excess is toxic for hematopoietic stem and progenitor cells (HSPCs). During embryogenesis, a small number of HSPCs are produced from the hemogenic endothelium, before they colonize a transient organ where they expand, for example the fetal liver in mammals. In this study, we use zebrafish to understand the molecular mechanisms that are important in the caudal hematopoietic tissue (equivalent to the mammalian fetal liver) to promote HSPC expansion. High levels of ROS are deleterious for HSPCs in this niche, however this is rescued by addition of antioxidants. We show that Cx41.8 is important to lower ROS levels in HSPCs. We also demonstrate a new role for ifi30, known to be involved in the immune response. In the hematopoietic niche, Ifi30 can recycle oxidized glutathione to allow HSPCs to dampen their levels of ROS, a role that could be conserved in human fetal liver.

Dithiophosphate-Induced Redox Conversions of Reduced and Oxidized Glutathione

Phosphorus species are potent modulators of physicochemical and bioactive properties of peptide compounds. O,O-diorganyl dithiophoshoric acids (DTP) form bioactive salts with nitrogen-containing biomolecules; however, their potential as a peptide modifier is poorly known. We synthesized amphiphilic ammonium salts of O,O-dimenthyl DTP with glutathione, a vital tripeptide with antioxidant, protective and regulatory functions. DTP moiety imparted radical scavenging activity to oxidized glutathione (GSSG), modulated the activity of reduced glutathione (GSH) and profoundly improved adsorption and electrooxidation of both glutathione salts on graphene oxide modified electrode. According to NMR spectroscopy and GC–MS, the dithiophosphates persisted against immediate dissociation in an aqueous solution accompanied by hydrolysis of DTP moiety into phosphoric acid, menthol and hydrogen sulfide as well as in situ thiol-disulfide conversions in peptide moieties due to the oxidation of GSH and reduction of GSSG. The thiol content available in dissolved GSH dithiophosphate was more stable during air oxidation compared with free GSH. GSH and the dithiophosphates, unlike DTP, caused a thiol-dependent reduction of MTS tetrazolium salt. The results for the first time suggest O,O-dimenthyl DTP as a redox modifier for glutathione, which releases hydrogen sulfide and induces biorelevant redox conversions of thiol/disulfide groups.

Effect of Chronic Exposure to Pesticide Methomyl on Antioxidant Defense System in Testis of Tilapia (Oreochromis niloticus) and Its Recovery Pattern

The chronic effect of environmental methomyl on the antioxidant system in testis of Nile tilapia (Oreochromis niloticus) and its recovery pattern was investigated. Tilapia were exposed to sublethal concentrations of 0.2, 2, 20 and 200 μgL−1 methomyl for 30 days and thereafter moved to methomyl-free water for 18 days. Antioxidant levels in testis, including glutathione peroxidase, catalase, glutathione-S-transferase, glutathione reductase, superoxide dismutase, reduced glutathione, oxidized glutathione were measured every 6 days during the period of exposure, and at 18 days after being transferred to methomyl-free water. The results showed that lower methomyl concentration (0.2 μgL−1) had no effect on the above antioxidants, thus 0.2 μgL−1 could be seen as NOAEL for methomyl to tilapia. However, higher methomyl concentration of 2, 20 and 200 μgL−1 could significantly influence the above antioxidants. Glutathione peroxidase and oxidized glutathione increased significantly. On the contrary, reduced glutathione decreased significantly. Catalase, superoxide dismutase, glutathione reductase, glutathione-S-transferase increased at lower methomyl (2 and 20 μgL−1), but decreased at higher methomyl (200 μgL−1). The recovery test showed that oxidative damage caused by lower methomyl of 2 and 20 μgL−1 was reversible, and oxidative damage caused by higher methomyl of 200 μgL−1 was irreversible within 18 days of recovery period.

Development and Validation of HPLC Method for Simultaneous Estimation of Reduced and Oxidized Glutathione in Bulk Pharmaceutical Formulation

The objective of this study was the development, optimization, and validation of a RP-HPLC method for the quantification of reduced glutathione (GSH) and oxidized glutathione (GSSG) in pharmaceutical formulations The separation utilized a C18 column at room temperature with absorption wavelength 210nm. The mobile phase was an isocratic flow of a 95:5 (v/v) mixture of 25mM phosphate buffer (pH 2.7) and methanol with flow rate at 1.0 mL/min. Validation of the method assessed with the methods ability in seven categories: linearity, range, limit of detection, limit of quantification, accuracy, precision, and selectivity. The method show an acceptable degree of linearity with r²=0.9994 and 0.999 over a concentration range of 10-200 μg/mL for GSH and GSSG respectively. The detection limit and quantification limit for GSH 20.7μg/mL and 69.24μg/mL and for GSSG 17.22μg/mL and 57.42μg/mL respectively. The percent recovery of the method was 99.98-100.93 %. Following validation, the method was employed in the determination of glutathione in pharmaceutical formulations in the form of a liposome. The proposed method offers a simple, accurate, and inexpensive way to quantify reduced glutathione.

Differences between Professional and Amateur Cyclists in Endogenous Antioxidant System Profile

Currently, no studies have examined the differences in endogenous antioxidant enzymes in professional and amateur cyclists and how these can influence sports performance. The aim of this study was to identify differences in endogenous antioxidants enzymes and hemogram between competitive levels of cycling and to see if differences found in these parameters could explain differences in performance. A comparative trial was carried out with 11 professional (PRO) and 15 amateur (AMA) cyclists. All cyclists performed an endogenous antioxidants analysis in the fasted state (visit 1) and an incremental test until exhaustion (visit 2). Higher values in catalase (CAT), oxidized glutathione (GSSG) and GSSG/GSH ratio and lower values in superoxide dismutase (SOD) were found in PRO compared to AMA (p < 0.05). Furthermore, an inverse correlation was found between power produced at ventilation thresholds 1 and 2 and GSSG/GSH (r = −0.657 and r = −0.635; p < 0.05, respectively) in PRO. Therefore, there is no well-defined endogenous antioxidant enzyme profile between the two competitive levels of cyclists. However, there was a relationship between GSSG/GSH ratio levels and moderate and submaximal exercise performance in the PRO cohort.

Effect of Rosmarinic Acid and Ionizing Radiation on Glutathione in Melanoma B16F10 Cells: A Translational Opportunity

To explain a paradoxical radiosensitizing effect of rosmarinic acid (RA) on the melanoma B16F10 cells, we analyzed the glutathione (GSH) intracellular production on this cell (traditionally considered radioresistant) in comparison with human prostate epithelial cells (PNT2) (considered to be radiosensitive). In PNT2 cells, the administration of RA increased the total GSH content during the first 3 h (p < 0.01) as well as increased the GSH/oxidized glutathione (GSSG) ratio in all irradiated cultures during all periods studied (1h and 3h) (p < 0.001), portraying an increase in the radioprotective capacity. However, in B16F10 cells, administration of RA had no effect on the total intracellular GSH levels, decreasing the GSH/GSSG ratio (p < 0.01); in addition, it caused a significant reduction in the GSH/GSSG ratio in irradiated cells (p < 0.001), an expression of radioinduced cell damage. In B16F10 cells, the administration of RA possibly activates the metabolic pathway of eumelanin synthesis that would consume intracellular GSH, thereby reducing its possible use as a protector against oxidative stress. The administration of this type of substance during radiotherapy could potentially protect healthy cells for which RA is a powerful radioprotector, and at the same time, cause significant damage to melanoma cells for which it could act as a radiosensitive agent.