A 78-year-old man with dementia experienced waxing and waning of symptoms with changes in altitude as he traveled from his home in the Rocky Mountains to lower elevations and back. To replicate the improvement in his symptoms with travel to lower elevations (higher pressure), the patient was treated with a near-identical repressurization in a hyperbaric chamber using compressed air. With four 1-h treatments at 1.3 Atmospheres Absolute (ATA) and concurrent administration of low-dose oral glutathione amino acid precursors, he recovered speech and showed improvement in activities of daily living. Regional broadcast media had documented his novel recovery. Nosocomial COVID-19 and withdrawal of hyperbaric air therapy led to patient demise 7 months after initiation of treatment. It is theorized that hyperbaric air therapy stimulated mitochondrial biochemical and physical changes, which led to clinical improvement.

Protein persulfidation is a thiol-based oxidative posttranslational modification (oxiPTM) that involves the modification of susceptible cysteine thiol groups present in peptides and proteins through hydrogen sulfide (H2S), thus affecting their function. Using sweet pepper (Capsicum annuum L.) fruits as a model material at different stages of ripening (immature green and ripe red), endogenous persulfidated proteins (persulfidome) were labeled using the dimedone switch method and identified using liquid chromatography and mass spectrometry analysis (LC-MS/MS). A total of 891 persulfidated proteins were found in pepper fruits, either immature green or ripe red. Among these, 370 proteins were exclusively present in green pepper, 237 proteins were exclusively present in red pepper, and 284 proteins were shared between both stages of ripening. A comparative analysis of the pepper persulfidome with that described in Arabidopsis leaves allowed the identification of 25% of common proteins. Among these proteins, glutathione reductase (GR) and leucine aminopeptidase (LAP) were selected to evaluate the effect of persulfidation using an in vitro approach. GR activity was unaffected, whereas LAP activity increased by 3-fold after persulfidation. Furthermore, this effect was reverted through treatment with dithiothreitol (DTT). To our knowledge, this is the first persulfidome described in fruits, which opens new avenues to study H2S metabolism. Additionally, the results obtained lead us to hypothesize that LAP could be involved in glutathione (GSH) recycling in pepper fruits.

BACKGROUND: Periodontal diseases are the most frequently diagnosed problem in cats. It has been well-established that periodontal diseases could not only cause various oral health issues but could also contribute to systemic diseases. Oxidative stress is a possible link between systemic diseases and periodontitis. Our study aimed to illustrate the influence of periodontitis on oxidative stress development in cats. Furthermore, the changes in the bacterial flora of the gums were investigated.
METHODS: Based on the clinical and laboratory examinations, fifty cats were divided into two groups normal (n = 25) and moderate to advanced periodontitis (n = 25). Serum total antioxidant capacity (TAC), total oxidant status (TOS), reduced (GSH) and oxidized glutathione (GSSG) were measured. In addition, samples were taken from the subgingival plaques of all cats for bacterial culture.
RESULTS: Serum TOS, GSSG, GSSG to GSH ratio, and oxidative stress index (OSI), calculated as the ratio of TOS to TAC in cats with periodontal disease were significantly higher, and TAC was significantly lower (p < 0.05) compared with controls. The results of bacterial culture indicated that the number of isolated bacterial colonies is higher in patients than in the control group. Additionally, the analysis of these data showed a positive association between periodontal index and oxidative stress.
CONCLUSIONS: Our results revealed that periodontitis in cats is related to a main oxidative stress. Furthermore, oxidant factors such as TOS and OSI, compared to antioxidant factors, may better indicate the presence of oxidative stress conditions in patients with periodontitis.

UNASSIGNED: Oxidative stress is involved in pathogenesis of some psychiatric disorders. To examine the role of oxidative stress in the etiopathogenesis of obsessive-compulsive disorder (OCD), we aimed to determine oxidative stress indices, including malondialdehyde (MDA) levels in serum and red blood cells (RBC) membrane, total antioxidant capacity (TAC), serum glutathione (GSH) levels, serum antioxidant vitamins (A and E), and Na+/K+-ATPase activity, in patients with the mentioned disorder vs. healthy controls.
UNASSIGNED: 39 OCD patients diagnosed based on Diagnostic and Statistical Manual of Mental Disorders (DSM-V) and 39 volunteer healthy subjects were included in this study. MDA levels in serum and RBC membrane were measured using fluorometric method. Serum TAC level, serum GSH level, and Na+/K+-ATPase activity were also measured using spectrophotometric methods. Serum levels of vitamins were calculated by reversed-phase high-performance liquid chromatography (RP-HPLC).
UNASSIGNED: There was a significantly higher MDA level in serum (p < 0.0001) and RBC membrane (p = 0.002) of OCD patients compared with those in controls. A significant reduction in vitamin A (p = 0.001) and vitamin E (p = 0.024) levels was found in OCD patients vs. controls. There was significantly lower activity of erythrocyte membrane Na+/K+-ATPase in RBC membrane of OCD patients vs. controls (p < 0.0001).
UNASSIGNED: Our findings indicate significantly higher levels MDA in both serum and RBC membrane, lower levels of serum vitamins A and E, and lower activity of membrane Na+/K+-ATPase in OCD patients compared to controls. These suggest an imbalance between oxidant and antioxidant factors in OCD patients that might play a fundamental role in the etiopathogenesis of OCD.

Autism spectrum disorder (ASD) is a type of neurodevelopmental disorder that has been diagnosed in an increasing number of children around the world. The existing data suggest that early diagnosis and intervention can improve ASD outcomes. The causes of ASD remain complex and unclear, and there are currently no clinical biomarkers for autism spectrum disorder. There is an increasing recognition that ASD might be associated with oxidative stress through several mechanisms including abnormal metabolism (lipid peroxidation) and the toxic buildup of reactive oxygen species (ROS). Glutathione acts as an antioxidant, a free radical scavenger and a detoxifying agent. This open-label pilot study investigates the tolerability and effectiveness of oral supplementation with OpitacTM gluthathione as a treatment for patients with ASD. The various aspects of glutathione OpitacTM glutathione bioavailability were examined when administered by oral routes. The absorption of glutathione from the gastrointestinal tract has been recently investigated. The results of this case series suggest that oral glutathione supplementation may improve oxidative markers, but this does not necessarily translate to the observed clinical improvement of subjects with ASD. The study reports a good safety profile of glutathione use, with stomach upset reported in four out of six subjects. This article discusses the role of the gut microbiome and redox balance in ASD and notes that a high baseline oxidative burden may make some patients poor responders to glutathione supplementation. In conclusion, an imbalance in redox reactions is only one of the many factors contributing to ASD, and further studies are necessary to investigate other factors, such as impaired neurotransmission, immune dysregulation in the brain, and mitochondrial dysfunction.

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Omics techniques have been increasingly recognized as promising tools for Next Generation Risk Assessment. Targeted metabolomics offer the advantage of providing readily interpretable mechanistic information about perturbed biological pathways. In this study, a high-throughput LC-MS/MS-based broad targeted metabolomics system was applied to study nitrofurantoin metabolic dynamics over time and concentration and to provide a mechanistic-anchored approach for point of departure (PoD) derivation. Upon nitrofurantoin exposure at five concentrations (7.5 µM, 15 µM, 20 µM, 30 µM and 120 µM) and four time points (3, 6, 24 and 48 h), the intracellular metabolome of HepG2 cells was evaluated. In total, 256 uniquely identified metabolites were measured, annotated, and allocated in 13 different metabolite classes. Principal component analysis (PCA) and univariate statistical analysis showed clear metabolome-based time and concentration effects. Mechanistic information evidenced the differential activation of cellular pathways indicative of early adaptive and hepatotoxic response. At low concentrations, effects were seen mainly in the energy and lipid metabolism, in the mid concentration range, the activation of the antioxidant cellular response was evidenced by increased levels of glutathione (GSH) and metabolites from the de novo GSH synthesis pathway. At the highest concentrations, the depletion of GSH, together with alternations reflective of mitochondrial impairments, were indicative of a hepatotoxic response. Finally, a metabolomics-based PoD was derived by multivariate PCA using the whole set of measured metabolites. This approach allows using the entire dataset and derive PoD that can be mechanistically anchored to established key events. Our results show the suitability of high throughput targeted metabolomics to investigate mechanisms of hepatoxicity and derive point of departures that can be linked to existing adverse outcome pathways and contribute to the development of new ones.

Considering the biological and ecological importance of Cu-thiol interactions and the discrepancies in previous research, this study focuses on Cu interactions with biologically and ecologically relevant thiols: glutathione (GSH), L-cysteine (L-cys), 3-mercaptopropionic acid (MPA), and thioacetic acid (TAA) in aqueous solution. The addition of Cu(II) to a thiol-containing solution led to a rapid reduction of Cu(II) and the formation of a Cu(I)-thiol complex. The mechanism of Cu(II) reduction and Cu(I) complex formation as well as the kinetics of Cu(I) oxidation strongly depend on the structural properties of the individual thiols investigated. The reducing power of the investigated thiols can be summarized as follows: L-cys ≅ GSH > MPA > TAA. The reaction order, with respect to Cu(I) oxidation, also changes over the time of the reaction course. The deviation of the reaction kinetics from the first order with respect to Cu(I) in the later stages of the reaction course can be attributed to a Fenton-like reaction occurring under low thiol concentration conditions. At high Cu:thiol ratios, in the case of GSH, L-cys, and MPA, the early stage of the reaction course is characterized by high Cu(I) stability, most likely as a result of Cu(I) complexation by the thiols present in excess in the reaction mixture.

BACKGROUND: Recurrent Aphthous Stomatitis (RAS) is an inflammatory lesion of the oral mucous lining, accounting for 5 to 25% of the chronic oral lesions. Studies have suggested that RAS patients have increased oxidative stress (OS) and impaired antioxidant capacity, and non-invasive screening using saliva assessment of oxidative stress and antioxidant capacity may be beneficial in RAS.
OBJECTIVE: This study determined total salivary antioxidant concentration and compared it to the total serum antioxidant levels in patients with RAS and controls.
METHODS: This was a case-control study of subjects with RAS and without RAS. Unstimulated mid-morning saliva was collected using the spitting method, and venous blood was collected into a plastic vacutainer. Saliva and blood samples were assayed for total oxidative stress (TOS), total antioxidant capacity (TAC), ferric reducing antioxidant power (FRAP) and glutathione.
RESULTS: A total of 46 subjects, 23 with RAS and 23 healthy controls, participated in the study. Twenty-five (54.35%) were males, and 21(45.65) were females aged 17 to 73 years. We identified an increase in salivary and serum TOS (10.06 ± 7.49, 8.26 ± 2.18/ 15.00 ± 8.92, 9.36 ± 3.55µmol/L) and OSI while the TAC (16.85 ± 1.97, 17.07 ± 2.36/17.07 ± 2.36, 2.97 ± 0.29mM/L) and significantly GSH (0.02 ± 0.02, 0.10 ± 0.02/0.10 ± 0.02/0.19 ± 0.11 µmol/ml) were decreased in serum and saliva of the RAS group compared to controls respectively. In addition, there were positive correlations between salivary and serum levels of FRAP r=0.588, p= 0.003 and glutathione r=0.703, p<0.001 in RAS subjects and controls.
CONCLUSIONS: Oxidative stress is associated with RAS, and saliva can be used as a biological marker for glutathione and FRAP.
BACKGROUND: La stomatite aphteuse récurrente (SAR) est une lésion inflammatoire de la muqueuse buccale qui représente 5 à 25 % des lésions buccales chroniques. Des études ont suggéré que les patients atteints de stomatite aphteuse récurrente présentent un stress oxydatif (SO) accru et une capacité antioxydante altérée, et qu’un dépistage non invasif utilisant l’évaluation salivaire du stress oxydatif et de la capacité antioxydante pourrait être bénéfique dans la stomatite aphteuse récurrente.
OBJECTIVE: Cette étude a déterminé la concentration totale d’antioxydants dans la salive et l’a comparée aux niveaux totaux d’antioxydants dans le sérum chez des patients atteints de SRA et chez des témoins.
UNASSIGNED: Il s’agit d’une étude cas-témoins portant sur des sujets atteints ou non du syndrome respiratoire aigu sévère. De la salive non stimulée a été recueillie en milieu de matinée par la méthode du crachat, et du sang veineux a été prélevé dans un vacutainer en plastique. Les échantillons de salive et de sang ont été analysés pour déterminer le stress oxydatif total (TOS), la capacité antioxydante totale (TAC), le pouvoir antioxydant réducteur ferrique (FRAP) et le glutathion.
UNASSIGNED: Au total, 46 sujets, 23 atteints de SRA et 23 témoins sains, ont participé à l’étude. Vingt-cinq (54,35 %) étaient des hommes et 21 (45,65) des femmes âgés de 17 à 73 ans. Nous avons identifié une augmentation des TOS salivaires et sériques (10.06 ± 7.49, 8.26 ± 2.18/ 15.00 ± 8.92, 9.36 ± 3.55µmol/L) et de l’OSI tandis que le TAC (16.85 ± 1.97, 17.07 ± 2.36/17.07 ± 2.36, 2. 97 ± 0.29mM/L) et significativement le GSH (0.02 ± 0.02, 0.10 ± 0.02/0.10 ± 0.02/0.19 ± 0.11 µmol/ml) ont été diminués dans le sérum et la salive du groupe RAS par rapport aux contrôles respectivement. En outre, il y avait des corrélations positives entre les niveaux salivaires et sériques de FRAP r=0,588, p= 0,003 et de glutathion r=0,703, p<0,001 chez les sujets RAS et les témoins.
CONCLUSIONS: Le stress oxydatif est associé au SAPR et la salive peut être utilisée comme marqueur biologique pour le glutathion et la FRAP.
UNASSIGNED: Stomatite aphteuse récurrente, Antioxydants, Salive, Stress oxydatif.

Environmental exposures often produce reactive electrophiles in vivo, leading to oxidative stress, which plays a major role in carcinogenesis. These electrophiles frequently form adducts with human albumin, which can be measured to assess in vivo oxidative stress. Here, we aimed to examine the associations between circulatory albumin adducts and acute myeloid leukemia (AML), the most common adult myeloid leukemia that showed consistent associations with environmental exposures. We conducted a nested case-control study of 52 incident AML cases and 103 controls matched on age, sex and race within two prospective cohorts: the CLUE and PLCO studies. We measured 42 untargeted albumin adducts in prediagnostic samples using liquid chromatography-high-resolution mass spectrometry. Circulatory albumin adducts were associated with AML in conditional logistic regression models. For instance, higher levels of Cys34 disulfide adduct of the S-γ-glutamylcysteine, a precursor of the essential antioxidant, glutathione were associated with a lower risk of AML (odds ratios [95% confidence intervals]) for the 1st, 2nd and 3rd tertiles were 1.0, 0.65 (0.31-1.36) and 0.31 (0.12-0.80), respectively (P-trend = .01). These associations were largely driven by effects present among cases diagnosed at or above the median follow-up time of 5.5 years. In conclusion, applying a novel approach to characterize exposures in the prediagnostic samples, we found evidence supporting the notion that oxidative stress may play a role in the pathogenesis of AML. Our findings offer insight into AML etiology and may be relevant in identifying novel therapeutic targets.