Thiol Antioxidant Research Articles

Effects of COVID-19 and medication used for treatment and symptom prevention on the antioxidant status.

It is known that an inflammatory response plays a key role in COVID-19 pathogenesis. An exacerbated inflammatory response can increase oxidative stress in cells. This study aimed to investigate the effects of COVID-19 on parameters of oxidative stress including non-protein thiol antioxidants (NPSH), protein thiols (PSH), total antioxidant capacity (TAC), advanced oxidation protein products (AOPP), myeloperoxidase (MPO), thiobarbituric acid reactive substances (TBARS), ascorbic acid, and reactive oxygen species (ROS) in plasma collected four to six weeks after the diagnosis. This cross-sectional study included a sex-matched sample of 296 adult individuals with 112 positives (cases) and 184 negatives (controls) for COVID-19. Oxidative stress parameters were peripherally analyzed according to previous methods. The results showed a decrease in NPSH (p = 0.004), TAC (p = 0.005), ROS (p < 0.001), and ascorbic acid (p < 0.001) in cases. TBARS were higher in moderate and severe cases of COVID-19 compared to asymptomatic and mild cases (p = 0.049). AOPP, PSH, and MPO were not significantly different between cases and controls. In the total sample, individuals who self-reported using medication to prevent or treat COVID-19 showed decreased NPSH (p = 0.034), TAC (p = 0.020), ascorbic acid (p = 0.010), and ROS (p = 0.001) compared to those who self-reported not using medication to prevent or treat COVID-19. In conclusion, individuals with COVID-19 had decreased antioxidant status. Furthermore, disease severity was associated with more lipid damage. Antioxidant therapies may be essential to prevent the impacts of COVID-19.

Excessive Weight Gain During Pregnancy Increased Ponoxarase 1 Level in Neonatal Cord Blood.

Maternal obesity is increasingly recognized as a risk factor for adverse fetal outcomes, primarily through its association with heightened oxidative stress. This study aimed to evaluate oxidative stress markers in umbilical cord blood of neonates born to obese mothers. Sixty-three pregnant women, who were of normal weight at the start of pregnancy but classified as obese at term, were included. Umbilical cord blood samples were collected immediately post-delivery and analyzed for serum oxidative stress markers (total oxidant status (TOS), total antioxidant status (TAS), paraoxanase (PON), aryl esterase, thiol, and catalase activities). Protein interaction networks were generated using Cytoscape (v3.10.3), and the overlapping proteins were further analyzed for functional annotations with ShinyGO (0.80). The top ten significantly enriched pathways were identified with a false discovery rate (FDR) threshold of <0.05. Significant associations were found between maternal BMI change and paraoxonase 1 (PON1) levels in umbilical cord blood, while no correlation was observed with other oxidative (total oxidant status) and antioxidant markers (total antioxidant status, aryl esterase, thiol, and catalase). Additionally, the correlation analysis showed a significant relationship between BMI change and fetal gestational age, but not with other demographic or clinical features. A total of 24 common protein interactors associated with PON1, obesity, and oxidative stress were identified. Functional annotation analysis revealed significant enrichment in antioxidant and oxidoreductase activities, along with pathways involved in insulin resistance, AGE-RAGE signaling, and atherosclerosis. Maternal obesity may specifically affect PON1 activity, potentially serving as a compensatory response to oxidative stress in neonates, suggesting PON1 as a possible biomarker for oxidative stress-related metabolic disturbances in neonates of obese mothers, with implications for monitoring and managing pregnancy outcomes in obese populations.

Nrf2 Regulates Basal Glutathione Production in Astrocytes.

Astrocytes produce and export glutathione (GSH), an important thiol antioxidant essential for protecting neural cells from oxidative stress and maintaining optimal brain health. While it has been established that oxidative stress increases GSH production in astrocytes, with Nrf2 acting as a critical transcription factor regulating key components of the GSH synthetic pathway, the role of Nrf2 in controlling constitutive GSH synthetic and release mechanisms remains incompletely investigated. Our data show that naïve primary mouse astrocytes cultured from the cerebral cortices of Nrf2 knockout (Nrf2-/-) pups have significantly less intracellular and extracellular GSH levels when compared to astrocytes cultured from Nrf2 wild-type (Nrf2+/+) pups. Key components of the GSH synthetic pathway, including xCT (the substrate-specific light chain of the substrate-importing transporter, system xc-), glutamate-cysteine ligase [catalytic (GCLc) and modifying (GCLm) subunits], were affected. To wit: qRT-PCR analysis demonstrates that naïve Nrf2-/- astrocytes have significantly lower basal mRNA levels of xCT and both GCL subunits compared to naïve Nrf2+/+ astrocytes. No change in mRNA levels of glutathione synthetase (GS) or the GSH exporting transporter, Mrp1, was found. Western blot analysis reveals reduced protein levels of both subunits of GCL, while (seleno)cystine uptake into Nrf2-/- astrocytes was reduced compared to Nrf2+/+ astrocytes, confirming decreased system xc- activity. These findings suggest that Nrf2 regulates the basal production of GSH in astrocytes through constitutive transcriptional regulation of GCL and xCT.

Oxidative stress induces plasma membrane phosphatidylserine externalization in canine erythrocytes in vitro, mitigated by thiol antioxidants.

To determine if oxidative stress induces phosphatidylserine (PS) externalization in canine erythrocytes and if exposure to antioxidants prevents such changes. This was an in vitro, experimental study using 5 healthy, adult, purpose-bred research Beagles. Fresh EDTA-anticoagulated blood samples were collected from each dog, and erythrocytes were harvested. For objective 1, erythrocytes were exposed to the pro-oxidant agents tert-butyl hydroperoxide (TBHP) at 2, 3, or 4 mM or 2,2'-azobis(2-amidinopropane) dihydrochloride at 30, 40, or 50 mM. For objective 2, erythrocytes were exposed to 3 mM TBHP and the antioxidant N-acetylcysteine-amide (NACA) at various concentrations (0, 1, or 3 mM). Erythrocytes incubated with benzoylbenzoyl-ATP were used as positive control, whereas erythrocytes incubated with sodium chloride medium with 0.1% bovine serum albumin, DMSO, and NACA were used as negative controls. Erythrocytes were stained with allophycocyanin-conjugated Annexin V, and PS externalization was assessed by flow cytometry. The degree of PS externalization of each sample was recorded as median fluorescence intensity and percentage of PS positivity. TBHP at 3 and 4 mM caused increased PS externalization in canine erythrocytes. 2,2'-Azobis(2-amidinopropane) dihydrochloride at all concentrations caused increased PS externalization. N-acetylcysteine-amide at all concentrations prevented significant PS externalization measured by median fluorescence intensity and percentage of PS positivity from erythrocytes exposed to TBHP. Oxidative stress causes PS externalization in canine erythrocytes, and NACA ameliorates this effect. Future studies are needed to determine if increased PS externalization in erythrocytes occurs in dogs with immune-mediated hemolytic anemia and its role in promoting thromboembolism.

N-acetylcysteine modulates markers of oxidation, inflammation and infection in tuberculosis.

Half the global tuberculosis health burden is due to post-tuberculosis lung disease. Host-directed therapies have been proposed to reduce this burden. N-acetylcysteine (NAC) provides the conditionally essential amino acid cysteine required for synthesis of glutathione, an antioxidant thiol. We recently reported clinical outcomes of a trial of adjunctive NAC in patients with pulmonary tuberculosis, finding that NAC improved the secondary endpoint of recovery of lung function. Here we report the effects of NAC on biomarkers of oxidation, inflammation, and infection in that trial. 140 adults with moderate or far-advanced pulmonary tuberculosis were randomly assigned to standard tuberculosis treatment with or without NAC 1200mg twice daily for months 1-4. Sputum and blood samples were obtained at specified intervals to measure total glutathione, MTB-induced cytokines, haemoglobin, whole blood mycobactericidal activity (WBA), and sputum MTB burden. NAC treatment rapidly increased total glutathione (P<.0001), but levels did not reach those of healthy volunteers (P<.001). NAC reduced MTB-induced TNF-α (P =.011) without affecting IL-10, and accelerated the recovery of hemoglobin in participants with low values on entry. NAC did not affect killing in ex vivo whole blood culture but did slow the clearance of MTB from sputum (P=0.003). Adjunctive NAC showed antioxidant and anti-inflammatory effects consistent with the amelioration of immunopathology seen in preclinical models. Two biomarkers of antimicrobial activity showed discordant results; neither demonstrated the enhanced antimicrobial effects seen preclinically. The reduction of oxidative stress and inflammation by NAC may explain its effects on the recovery of lung function post-TB.

The effect of N-acetylcysteine on inflammatory and oxidative markers in patients receiving hemodialysis; a single-arm clinical trial study

Introduction: Oxidative stress is common in patients with chronic kidney disease, especially those that need hemodialysis. Due to the increased chance of oxidative stress and inflammation following dialysis, the risk of developing atherosclerosis and heart disease is higher in these patients. In the case of a chronic kidney disease and hemodialysis, highly sensitive C-reactive protein (hs-CRP) as a marker of inflammation and malondialdehyde (MDA) can be considered as an indicator for oxidative stress. N-acetyl cysteine (NAC) is a thiol antioxidant acting as a free radical scavenger. There are conflicting results regarding the effect of NAC on inflammation and oxidative stress. Objectives: This study was designed to evaluate the effect of this drug on hs-CRP and MDA in patients undergoing hemodialysis. Patients and Methods: This single-arm clinical trial study was performed on 26 patients receiving hemodialysis. The patients were treated with NAC 600 mg twice a day for two months. They were tested before the treatment and two months later. The data were analyzed using SPSS (version 22). Chi-square and paired T-tests were also employed for the statistical analysis of the data. Moreover, P value of &lt;0.05 were considered statistically significant. Results: In this study, 26, out of 32, participants completed the study and were included in the final analysis. The results showed that, compared to baseline, treatment with NAC significantly reduced albumin (P=0.025) and hs-CRP (P=0.003). Moreover, supplementation with NAC significantly increased hemoglobin (P=0.005), serum iron (P=0.002), transferrin saturation (P&lt;0.001), and calcium (P=0.026). However, no significant difference was observed at the end of the study in white blood cells (WBC; P=0.337), platelets (P=0.809), ferritin (P=0.797), calcium-phosphorus product (Ca×P; P=0.93), triglycerides (P=0.604), total cholesterol (P=0.411), low-density lipoprotein (LDL; P=0.145), high-density lipoprotein (HDL; P=1.00), and malondialdehyde (MDA; P=0.960). Conclusion: The present survey suggests that NAC may be an effective option in managing hemoglobin, serum iron, transferrin saturation, calcium, albumin, and hs-CRP in patients receiving hemodialysis. Further researches are needed to confirm the veracity of our findings. Trial Registration: The trial protocol was approved in the Iranian registry of clinical trial (identifier: IRCT2016111529812N2; https://irct.behdasht.gov.ir/trial/23866, ethical code; 17/1/257428).

Integrated roles of nitric oxide and melatonin in enhancing chromium resilience in cotton plants: modulation of thiol metabolism and antioxidant responses.

Chromium (Cr) is a hazardous metal found in various oxidation states, posing significant environmental and health risks. The study focuses on understanding how melatonin (MT), known for its diverse functions, including stress alleviation and antioxidant properties, interacts with nitric oxide (NO) to regulate sulfur metabolism and enhance cotton resilience under Cr toxicity. Cr toxicity negatively affected plant growth and photosynthesis and induced oxidative stress. MT treatment ameliorated these effects by enhancing photosynthetic pigments and gas exchange traits and upregulating the activities of antioxidant enzymes and the expression of FeSOD, CuZnSOD, and APX1. Moreover, MT reduced Cr accumulation in leaves, protecting photosynthetic organs from direct toxicity. Additionally, MT promotes the level of sulfur-based defense substances like glutathione (GSH) and phytochelatins (PC), which arecrucial for detoxifying heavy metals. This is achieved by upregulating genes involved in cysteine metabolism (CYC1, CYC2, CAS1, CAS2, DES1, DES2, and SSCS), increasing cysteine availability for GSH and PC synthesis, and enhancing Cr sequestration in vacuoles. However, when the inhibitor of MT biosynthesis (p-CPA) and NO scavenger (cPTIO) were used along with MT in Cr-stressed plants, they hindered the stimulatory effects of MT. The study highlights the importance of the NO-MT interaction in mediating these protective effects, indicating a potential signaling role for NO in plant defense mechanisms against Cr toxicity. Overall, the findings reveal that MT fertilizing may serve as an effective strategy to enhance Cr resistance in cotton plants, with NO potentially playing a signaling role in this response pathway.

Assessing antioxidant responses in C6 and U-87 MG cell lines exposed to high copper levels

Copper excess has been tested as an anticancer therapy, due to its properties to generate oxidative stress resulting in tumoral cell death. Thus, this study aimed to evaluate the impact of copper excess on oxidative stress and antioxidant responses in glioma cells, establishing the antioxidant system as a target of copper toxicity in tumoral cells. C6 and U-87 MG cells were exposed to CuSO4 (0–600 μM) for 24-48 h. SOD, CAT, GPx, GR, and CK activities, protein and non-protein thiol levels (PSH and NPSH), and O2− production were assessed, alongside SOD1, GPx1, and GR gene expression. Results revealed a decrease in GPx, GR, and CAT activity after CuSO4 exposure in both cell lines over 24-48 h, while SOD activity initially increased, then declined after 48 h. CK activity was also decreased in C6 cells. NPSH and PSH levels dropped after 24 h, and O2− production was observed in all CuSO4 concentrations. GR mRNA was reduced in both cell lines, contrasting with increased GPx1 mRNA in C6. U-87 MG cells exhibited higher levels of SOD1 mRNA, while C6 cells displayed lower expression. Our findings suggest that copper excess limits antioxidant enzyme activity and thiol levels, particularly in the C6 cells, likely attributable to oxidative stress or direct copper-enzyme interactions. Moreover, our results imply differences in copper toxicity regarding the cell lineage used, highlighting the importance of analyzing high copper levels effects in different models. Moreover, it could be proposed that the antioxidant system is a target of copper toxicity, contributing to glioma cell death.

Salivary redox biomarkers of overweight and obese adults in response to prebiotics intervention

Overweight and obesity are fast-growing risk to health. Its occurrence and prevalence are positively correlated to oxidative stress and inflammation. Saliva, as a crucial biological fluid, contains numerous redox biomarkers related to overweight and obesity(1) and is consistent with the corresponding biomarkers in blood(2). The prebiotics have been found to regulate the energy metabolism and reduce the severity of obesity. Their influences on salivary redox homeostasis, however, remain unclear. This study set out to investigate the changes in salivary redox biomarkers of overweight/obese Chinese adults in response to prebiotic intervention.In total 102 overweight and obese adults (BMI ≥ 26.5, male: female = 48:54) were recruited and randomly assigned to intervention group and placebo control. The intervention group received a prebiotics cocktail (10 g per serving, containing 3.6 g of inulin, 3.6 g of resistant dextrin, 0.8 g of oat fiber, 0.8 g of psyllium husk), while the control group received a placebo, 3 times per day for three months. Their saliva samples before and after intervention were collected by natural flow method and quantified for the salivary flow rate, total protein content, and salivary redox biomarkers, namely ferric-reducing antioxidant power (FRAP), thiol, uric acid, malondialdehyde, glutathione (GSH) levels, and superoxide dismutase (SOD) enzyme activity. There are 32 participants has completed the intervention while the other 70 participants are still ongoing.The data collected to date showed an average weight reduction of 5.37 kg in the intervention group and 0.72 kg in the placebo control, with a significantly different BMI (p &lt; 0.05). The intervention group showed significant decreases in salivary uric acid and malondialdehyde (p &lt; 0.05), and significant increases in FRAP, GSH levels, and SOD enzyme activity (p &lt; 0.05), while no significant differences were found among other biomarkers. It is worth noting that the salivary flow rate increased slightly while gaining the weight loss, although not significantly. Upon completion of the study, the salivary attributes will be correlated with gut microbiome profile to interpret the link between redox homeostasis in body fluids and prebiotics-caused gut microbial alternation.This study provides new insights in the redox biomarkers of overweight or obese adults, particularly in response to the prebiotic intervention and the subsequent weight loss. It may facilitate the establishment of noninvasive methods for determination of the redox biomarkers of obese patients and evaluation of dietary intervention.

α4 Nicotinic Acetylcholine Receptors in Lipopolysaccharide-Related Lung Inflammation

Sepsis remains an important healthcare challenge. The lungs are often affected in sepsis, resulting in acute lung injury characterized by inflammation. Mechanisms involving lipopolysaccharide (LPS) stimulation of toll-like receptor (TLR) signaling with induction of proinflammatory pathways have been implicated in this process. To date, however, studies targeting these pathways have failed to improve outcomes. We have found that LPS may also promote lung injury through the activation of α4 nicotinic acetylcholine receptors (α4 nAChRs) in immune cells. We observed increased expression of α4 nAChRs in human THP-1 monocytic cells exposed to LPS (100 ng/mL, 24 h). We also observed that LPS stimulated the expression of other relevant genes, including tumor necrosis factor-α, interleukin-1β, plasminogen activator inhibitor-1, the solute carrier family 7 member 11, extracellular superoxide dismutase, and transforming growth factor-β1. Of interest, dihydro-β-erythroidine hydrobromide (DHβE), a specific chemical inhibitor of α4 nAChRs, inhibited the LPS-induced expression of these genes. We generated mice with a global knockout mutation of the α4 nAChR subunit in the C57BL/6 background using CRISPR/Cas9 technology. The lungs of these LPS-treated animals demonstrated a reduction in the expression of the above-mentioned genes when compared with the lungs of wild-type animals. In support of the role of oxidative stress, we observed that LPS induced expression of the cystine transporter Slc7a11 in both THP-1 cells and in wild-type mouse lungs. The effects of LPS on THP-1 cells were blocked by the thiol antioxidant N-acetylcysteine and mimicked by redox stress. Importantly, the induction of IL-1β by redox stress was inhibited by the α4 nAChR inhibitor DHβE. Finally, we showed that LPS stimulated calcium influx in THP-1 cells, which was blocked by the α4 nAChR inhibitor. Our observations suggest that LPS promotes lung injury by stimulating redox stress, which activates α4 nAChR signaling and drives proinflammatory cytokine expression.

An Oxidative Stress Study on Curcumin and NanoCurcumin against Aluminum Phosphide-induced Kidney Injury in Rats: The Role of SIRT1/FOXO3 Signaling Pathway in Nephrotoxicity.

In this study, we have investigated the aluminium phosphide (ALP) toxicity on Renal Function and oxidative stress in kidney tissue of male rats and the possible protective role of Curcumin and nanoCurcumin against ALP-induced nephrotoxicity. Thirty-six adult male rats were divided into 6 groups (n=6). ALP (2 mg/kg oral administration) and control groups received Curcumin and nanoCurcumin (oral administration 100 mg/kg) or without it. After seven days of treatment, kidney parameters, oxidative stress biomarkers, and expression level of sirtuins1 (SIRT1)/Forkhead box protein O1 (FoxO1) pathway genes were evaluated in kidney tissue. In addition, histopathological changes in the kidney tissues were assayed. In the ALP group, compared to the control group, lipid peroxidation levels, urea, and creatinine were increased, and total antioxidant capacity and thiol groups decreased significantly p < 0.05. In Curcumin and nanoCurcumin groups compared to the ALP group, lipid peroxidation and creatinine decreased significantly p < 0.05. Also, Curcumin and nanoCurcumin improved the tissue damage caused by ALP. NanoCurcumin modulated the effect of ALP on the gene expression levels in SIRT1/FoxO1. The present study showed that ALP intoxication in kidney tissue can induce oxidative damage. Moreover, Curcumin and nanocurcumin, as potential antioxidants, can be effective therapeutics in ALP-induced nephrotoxicity.

Analytical Methods for Assessing Thiol Antioxidants in Biological Fluids: A Review.

Redox metabolism is an integral part of the glutathione system, encompassing reduced and oxidized glutathione, hydrogen peroxide, and associated enzymes. This core process orchestrates a network of thiol antioxidants like thioredoxins and peroxiredoxins, alongside critical thiol-containing proteins such as mercaptoalbumin. Modifications to thiol-containing proteins, including oxidation and glutathionylation, regulate cellular signaling influencing gene activities in inflammation and carcinogenesis. Analyzing thiol antioxidants, especially glutathione, in biological fluids offers insights into pathological conditions. This review discusses the analytical methods for biothiol determination, mainly in blood plasma. The study includes all key methodological aspects of spectroscopy, chromatography, electrochemistry, and mass spectrometry, highlighting their principles, benefits, limitations, and recent advancements that were not included in previously published reviews. Sample preparation and factors affecting thiol antioxidant measurements are discussed. The review reveals that the choice of analytical procedures should be based on the specific requirements of the research. Spectrophotometric methods are simple and cost-effective but may need more specificity. Chromatographic techniques have excellent separation capabilities but require longer analysis times. Electrochemical methods enable real-time monitoring but have disadvantages such as interference. Mass spectrometry-based approaches have high sensitivity and selectivity but require sophisticated instrumentation. Combining multiple techniques can provide comprehensive information on thiol antioxidant levels in biological fluids, enabling clearer insights into their roles in health and disease. This review covers the time span from 2010 to mid-2024, and the data were obtained from the SciFinder® (ACS), Google Scholar (Google), PubMed®, and ScienceDirect (Scopus) databases through a combination search approach using keywords.

Decreased glutathione synthesis in granulosa cells, but not oocytes, of growing follicles decreases fertility in mice†.

Prior studies showed that mice deficient in the modifier subunit of glutamate cysteine ligase (Gclm), the rate-limiting enzyme in synthesis of the thiol antioxidant glutathione, have decreased ovarian glutathione concentrations, chronic ovarian oxidative stress, poor oocyte quality resulting in early preimplantation embryonic mortality and decreased litter size, and accelerated age-related decline in ovarian follicle numbers. Global deficiency of the catalytic subunit of this enzyme, Gclc, is embryonic lethal. We tested the hypothesis that granulosa cell- or oocyte-specific deletion of Gclc recapitulates the female reproductive phenotype of global Gclm deficiency. We deleted Gclc in granulosa cells or oocytes of growing follicles using Gclc floxed transgenic mice paired with Amhr2-Cre or Zp3-Cre alleles, respectively. We discovered that granulosa cell-specific deletion of Gclc in Amhr2Cre;Gclc(f/-) mice recapitulates the decreased litter size observed in Gclm-/- mice but does not recapitulate the accelerated age-related decline in ovarian follicles observed in Gclm-/- mice. In addition to having lower glutathione concentrations in granulosa cells, Amhr2Cre;Gclc(f/-) mice also had decreased glutathione concentrations in oocytes. By contrast, oocyte-specific deletion of Gclc in Zp3Cre;Gclc(f/-) mice did not affect litter size or accelerate the age-related decline in follicle numbers, and these mice did not have decreased oocyte glutathione concentrations, consistent with transport of glutathione between cells via gap junctions. The results suggest that glutathione deficiency at earlier stages of follicle development may be required to generate the accelerated follicle depletion phenotype observed in global Gclm null mice.

Selenate simultaneously alleviated cadmium and arsenic accumulation in rice (Oryza sativa L.) via regulating transport genes

Cadmium (Cd) and arsenic (As) have contrasting biogeochemical behaviors in paddy soil, which posed an obstacle for reducing their accumulation in rice (Oryza sativa L.) simultaneously. In this study, selenate exhibited a more effective ability than selenite on simultaneous alleviation of Cd and As accumulation in rice under Cd-As co-exposure, and the mechanisms need to be further investigated. The results showed that selenate significantly decreased the root Cd and As contents by 59%–83% and 43%–72% compared to Cd-As compound exposure, respectively. Correspondingly, it significantly down-regulated the expression of uptake-related genes OsNramp5 (87.1%) and OsLsi1 (95.5%) in rice roots. Decreases in Cd (64.5%) and As (16.2%) contents in shoots were also found after selenate addition. Moreover, selenate may promoted the reduction of As(V) to As(Ⅲ) and As(III) efflux to the external medium, resulting in decreased As accumulation and As(Ⅲ) proportion in rice shoots and roots. In addition, selenate could promote the binding of Cd (by 14%–24%) and As (by 9%–15%) in the cell wall, and significantly reduced the oxidative stress by elevating levels of antioxidant enzymes (by 10%–105%) and thiol compounds (by 6%–210%). Additionally, selenate significantly down-regulated the expression of OsNramp1 (49.3%) and OsLsi2 (82.1%) associated with Cd and As transport in rice. These findings suggest selenate has the potential to be an effective material for the simultaneous reduction of Cd and As accumulation in rice under Cd-As co-contamination.

Synergistic Antioxidant Effects of Cysteine Derivative and Sm-Cluster for Food Applications.

The incorporation of antioxidants in food products is essential to prevent or delay deterioration, thereby addressing food spoilage. Thiol compounds, recognized for their natural antioxidant properties, are widely used in various foods; however, their antioxidant capacity is often limited. This study investigates the potential enhancement of thiol antioxidant capacity through the addition of a soluble, low-toxic inorganic Sm-cluster. Our findings demonstrate that the Sm-cluster significantly bolsters the antioxidant efficacy of thiol compounds. We explored, for the first time, the in vitro antioxidant activities of an Sm-oxo/hydroxy cluster combined with a cysteine derivative for potential food applications. The composition exhibited a robust inhibition of aromatic aldehyde flavor compound oxidation and displayed strong, dose-dependent DPPH (2,2-diphenyl-1-picrylhydrazine) radical scavenging activity. Notably, the antioxidant activity of the Sm-cluster/cysteine derivative was further enhanced under strong visible light conditions, which typically increased the likelihood of oxidation. These results suggest that the combination of inorganic cluster and thiol compounds presents a promising natural alternative to traditional antioxidants in the food industry.

Therapeutic Potential of Pentoxifylline in Paraquat-Induced Pulmonary Toxicity: Role of the Phosphodiesterase Enzymes.

Pentoxifylline (PTX), a non-selective phosphodiesterase inhibitor, has demonstrated protective effects against lung injury in animal models. Given the significance of pulmonary toxicity resulting from paraquat (PQ) exposure, the present investigation was designed to explore the impact of PTX on PQ-induced pulmonary oxidative impairment in male mice.Following preliminary studies, thirty-six mice were divided into six groups. Group 1 received normal saline, group 2 received a single dose of PQ (20 mg/kg; i.p.), and group 3 received PTX (100 mg/kg/day; i.p.). Additionally, treatment groups 4-6 were received various doses of PTX (25, 50, and 100 mg/kg/day; respectively) one hour after a single dose of PQ. After 72 hours, the animals were sacrificed, and lung tissue was collected.PQ administration caused a significant decrease in hematocrit and an increase in blood potassium levels. Moreover, a notable increase was found in the lipid peroxidation (LPO), nitric oxide (NO), and myeloperoxidase (MPO) levels, along with a notable decrease in total thiol (TTM) and total antioxidant capacity (TAC) contents, catalase (CAT) and superoxide dismutase (SOD) enzymes activity in lung tissue. PTX demonstrated the ability to improve hematocrit levels; enhance SOD activity and TTM content; and decrease MPO activity, LPO and NO levels in PQ-induced pulmonary toxicity. Furthermore, these findings were well-correlated with the observed lung histopathological changes.In conclusion, our results suggest that the high dose of PTX may ameliorate lung injury by improving the oxidant/antioxidant balance in animals exposed to PQ.

Cryo-EM structure of cadmium-bound human ABCB6

ATP-binding cassette transporter B6 (ABCB6), a protein essential for heme biosynthesis in mitochondria, also functions as a heavy metal efflux pump. Here, we present cryo-electron microscopy structures of human ABCB6 bound to a cadmium Cd(II) ion in the presence of antioxidant thiol peptides glutathione (GSH) and phytochelatin 2 (PC2) at resolutions of 3.2 and 3.1 Å, respectively. The overall folding of the two structures resembles the inward-facing apo state but with less separation between the two halves of the transporter. Two GSH molecules are symmetrically bound to the Cd(II) ion in a bent conformation, with the central cysteine protruding towards the metal. The N-terminal glutamate and C-terminal glycine of GSH do not directly interact with Cd(II) but contribute to neutralizing positive charges of the binding cavity by forming hydrogen bonds and van der Waals interactions with nearby residues. In the presence of PC2, Cd(II) binding to ABCB6 is similar to that observed with GSH, except that two cysteine residues of each PC2 molecule participate in Cd(II) coordination to form a tetrathiolate. Structural comparison of human ABCB6 and its homologous Atm-type transporters indicate that their distinct substrate specificity might be attributed to variations in the capping residues situated at the top of the substrate-binding cavity.

Changes in biomarkers of the redox status in whole blood and red blood cell lysates in canine hypothyroidism

Hypothyroidism is the most commonly diagnosed endocrine disease in dogs. The objective of this study was to evaluate the changes in the redox status in canine hypothyroidism using whole blood (WB) and red blood cell (RBCs) lysates. For this purpose, a panel of five antioxidants and five oxidants biomarkers was measured in WB and RBCs lysates of 30 dogs with hypothyroidism, 26 dogs with non-thyroidal illnesses and 15 healthy dogs. The antioxidants measured were cupric reducing antioxidant capacity (CUPRAC), ferric reducing ability of plasma (FRAP), Trolox equivalent antioxidant capacity (TEAC), thiol and paraoxonase type-1 (PON-1). Oxidants measured include the total oxidant status (TOS), peroxide-activity (POX-Act), reactive oxygen-derived metabolites (d-ROMs), advanced oxidation protein products (AOPP) and thiobarbituric acid reactive substances (TBARS). WB showed a significant decrease of the antioxidants CUPRAC, TEAC and thiol, and also an increase in TBARS and a decrease in AOPP in dogs with hypothyroidism compared to healthy dogs. Meanwhile, RBCs lysates showed a significant increase in FRAP and PON-1 in dogs with hypothyroidism. The changes in the redox biomarkers in this study show that WB in canine hypothyroidism had a higher number of changes in biomarkers of the redox status than RBCs lysates, making it a promising sample type for the evaluation of the redox status in this disease. In addition, WB is easier and simpler to process than RBCs lysates and unlike serum, it does not have any hemolysis interference.

Redox Homeostasis Alteration Is Restored through Melatonin Treatment in COVID-19 Patients: A Preliminary Study.

Type II pneumocytes are the target of the SARS-CoV-2 virus, which alters their redox homeostasis to increase reactive oxygen species (ROS). Melatonin (MT) has antioxidant proprieties and protects mitochondrial function. In this study, we evaluated whether treatment with MT compensated for the redox homeostasis alteration in serum from COVID-19 patients. We determined oxidative stress (OS) markers such as carbonyls, glutathione (GSH), total antioxidant capacity (TAC), thiols, nitrites (NO2-), lipid peroxidation (LPO), and thiol groups in serum. We also studied the enzymatic activities of glutathione peroxidase (GPx), glutathione-S-transferase (GST), reductase (GR), thioredoxin reductase (TrxR), extracellular superoxide dismutase (ecSOD) and peroxidases. There were significant increases in LPO and carbonyl quantities (p ≤ 0.03) and decreases in TAC and the quantities of NO2-, thiols, and GSH (p < 0.001) in COVID-19 patients. The activities of the antioxidant enzymes such as ecSOD, TrxR, GPx, GST, GR, and peroxidases were decreased (p ≤ 0.04) after the MT treatment. The treatment with MT favored the activity of the antioxidant enzymes that contributed to an increase in TAC and restored the lost redox homeostasis. MT also modulated glucose homeostasis, functioning as a glycolytic agent, and inhibited the Warburg effect. Thus, MT restores the redox homeostasis that is altered in COVID-19 patients and can be used as adjuvant therapy in SARS-CoV-2 infection.

Gut bacteria exacerbates TNBS-induced colitis and kidney injury through oxidative stress

Gut microbiota has been implicated in the initiation and progression of various diseases; however, the underlying mechanisms remain elusive and effective therapeutic strategies are scarce. In this study, we investigated the role and mechanisms of gut microbiota in TNBS-induced colitis and its associated kidney injury while evaluating the potential of dietary protein as a therapeutic intervention. The intrarectal administration of TNBS induced colitis in mice, concurrently with kidney damage. Interestingly, this effect was absent when TNBS was administered intraperitoneally, indicating a potential role of gut microbiota. Depletion of gut bacteria with antibiotics significantly attenuated the severity of TNBS-induced inflammation, oxidative damage, and tissue injury in the colon and kidneys. Mechanistic investigations using cultured colon epithelial cells and bone-marrow macrophages unveiled that TNBS induced cell oxidation, inflammation and injury, which was amplified by the bacterial component LPS and mitigated by thiol antioxidants. Importantly, in vivo administration of thiol-rich whey protein entirely prevented TNBS-induced colonic and kidney injury. Our findings suggest that gut bacteria significantly contribute to the initiation and progression of colitis and associated kidney injury, potentially through mechanisms involving LPS-induced exaggeration of oxidative cellular damage. Furthermore, our research highlights the potential of dietary thiol antioxidants as preventive and therapeutic interventions.