Mitochondrial-targeted curcumin inhibits T-cell activation via Nrf2 and inhibits graft-versus-host-disease in a mouse model.

Anti-inflammatory and immune suppressive agents are required to moderate hyper-activation of lymphocytes under disease conditions or organ transplantation. However, selective disruption of mitochondrial redox has not been evaluated as a therapeutic strategy for suppression of T-cell-mediated pathologies. Using mitochondrial targeted curcumin (MitoC), we studied the effect of mitochondrial redox modulation on T-cell responses by flow cytometry, transmission electron microscopy, transcriptomics, and proteomics, and the role of Nrf2 was studied using Nrf2- /- mice. MitoC decreased mitochondrial TrxR activity, enhanced mitochondrial ROS (mROS) production, depleted mitochondrial glutathione, and suppressed activation-induced increase in mitochondrial biomass. This led to suppression of T-cell responses and metabolic reprogramming towards Treg differentiation. MitoC induced nuclear translocation and DNA binding of Nrf2, leading to upregulation of Nrf2-dependent genes and proteins. MitoC-mediated changes in mitochondrial redox and modulation of T-cell responses are abolished in Nrf2- /- mice. Restoration of mitochondrial thiols abrogated inhibition of T-cell responses. MitoC suppressed alloantigen-induced lymphoblast formation, inflammatory cytokines, morbidity, and mortality in acute graft-versus-host disease mice. Disruption of mitochondrial thiols but not mROS increase inculcates an Nrf2-dependent immune-suppressive disposition in T cells for the propitious treatment of graft-versus-host disease.

Inhibition of O-acetylserine (thiol) lyase as a promising new mechanism of action for herbicides.

Enzymes of the sulfur assimilation pathway of plants have been identified as potential targets for herbicide development, given their crucial role in synthesizing amino acids, coenzymes, and various sulfated compounds. In this pathway, O-acetylserine (thiol) lyase (OAS-TL; EC 2.5.1.47) catalyzes the synthesis of L-cysteine through the incorporation of sulfate into O-acetylserine (OAS). This study used an in silico approach to select seven inhibitors for OAS-TL. The in silico experiments revealed that S-benzyl-L-cysteine (SBC) had a better docking score (-7.0 kcal mol-1) than the substrate OAS (-6.6 kcal mol-1), indicating its suitable interaction with the active site of the enzyme. In vitro experiments showed that SBC is a non-competitive inhibitor of OAS-TL from Arabidopsis thaliana expressed heterologously in Escherichia coli, with a Kic of 4.29 mM and a Kiu of 5.12 mM. When added to the nutrient solution, SBC inhibited the growth of maize and morning glory weed plants due to the reduction of L-cysteine synthesis. Remarkably, morning glory was more sensitive than maize. As proof of its mechanism of action, L-cysteine supplementation to the nutrient solution mitigated the inhibitory effect of SBC on the growth of morning glory. Taken together, our data suggest that reduced L-cysteine synthesis is the primary cause of growth inhibition in maize and morning glory plants exposed to SBC. Furthermore, our findings indicate that inhibiting OAS-TL could potentially be a novel approach for herbicidal action.

Ellagic acid mitigates rotenone-induced damage via modulating mitochondria function in Drosophila melanogaster.

Constant, systematic exposure to rotenone has been utilized in animal models to induce Parkinsonism. Ellagic acid is a polyphenol with anti-inflammatory and antioxidative properties which is found in numerous natural fruits. Here, we investigated the therapeutic effects of ellagic acid in rotenone-induced toxicity in Drosophila melanogaster evaluating their antioxidant and mitoprotective properties. Adult flies were treated with rotenone and ellagic acid through their diet for 7 days, thereafter markers of neurotoxicity (acetylcholinesterase, monoamine oxidase, tyrosine hydroxylase), antioxidant and oxidative stress markers (hydrogen peroxide, nitric oxide, lipid peroxidation, protein carbonyl contents, catalase, total thiol, and nonprotein thiol) was measured. Mitochondrial respiration was also evaluated in the flies. Survival assay was carried out with both genders of the flies, and we observed a significant increase in the survival rate of flies exposed to both rotenone and ellagic acid when compared with the increased mortality rate in the groups exposed to rotenone alone. The impaired locomotion, altered redox status, and enzymes of neurotoxicity induced by rotenone were significantly ameliorated by ellagic acid to levels comparable to the control. In addition, rotenone-induced complex 1 inhibition and altered bioenergetic state were restored upon ellagic acid supplementation. These findings show the beneficial properties of ellagic acid against pesticides induced toxicity.

Diosmin and Bromelain Stimulate Glutathione and Total Thiols Production in Red Blood Cells.

Diosmin and bromelain are bioactive compounds of plant origin with proven beneficial effects on the human cardiovascular system. We found that diosmin and bromelain slightly reduced total carbonyls levels and had no effect on TBARS levels, as well as slightly increased the total non-enzymatic antioxidant capacity in the RBCs at concentrations of 30 and 60 µg/mL. Diosmin and bromelain induced a significant increase in total thiols and glutathione in the RBCs. Examining the rheological properties of RBCs, we found that both compounds slightly reduce the internal viscosity of the RBCs. Using the MSL (maleimide spin label), we revealed that higher concentrations of bromelain led to a significant decrease in the mobility of this spin label attached to cytosolic thiols in the RBCs, as well as attached to hemoglobin at a higher concentration of diosmin, and for both concentrations of bromelain. Both compounds tended to decrease the cell membrane fluidity in the subsurface area, but not in the deeper regions. An increase in the glutathione concentration and the total level of thiol compounds promotes the protection of the RBCs against oxidative stress, suggesting that both compounds have a stabilizing effect on the cell membrane and improve the rheological properties of the RBCs.

Assessment of health risk, genotoxicity, and thiol compounds in Trigonella foenum-graecum (Fenugreek) under arsenic stress.

Arsenic (As) traces have been reported worldwide in vegetables and crops cultivated in As-polluted soils. Being carcinogenic, the presence of As in edibles is of great concern as it ultimately reaches humans and animals through the food chain. Besides, As toxicity adversely affects the growth, physiology, metabolism, and productivity of crops. In the present study, Trigonella foenum-graecum (Fenugreek) was exposed to the As stress (0, 50, 100, and 150 µM sodium arsenate) for a week. Further, evaluation of As accumulation in roots and shoots, magnitude and visualization of oxyradicals, and thiol-based defence offered by Fenugreek was assessed. The root and leaf accumulated 258-453 µg g-1 dry wt (DW) and 81.4-102.1 µg g-1 DW of As, respectively. An arsenic-mediated decline in the growth index and increase in oxidative stress was noted. Arsenic stress modulated the content of thiol compounds; especially cysteine content increased from 0.36 to 0.43 µmole g-1 FW protein was noted. Random Amplified Polymorphic DNA (RAPD)-based analysis showed DNA damage in As-treated plants. Health risk assessment parameters showed that As concentration in the consumable plant shoot was below the critical hazard level (hazard quotient < 1). Moreover, T. foenum-graecum showed varied responses to As-induced oxidative stress with applied concentrations (150 µM being more toxic than lower concentrations). In addition, the RAPD profile and level of thiol compounds were proved significant biomarkers to assess the As toxicity in plants. The conclusion of this study will help users of fenugreek to have a clue and create awareness regarding the consumption.

Dietary-derived vitamin B12 protects Caenorhabditis elegans from thiol-reducing agents.

BACKGROUND: One-carbon metabolism, which includes the folate and methionine cycles, involves the transfer of methyl groups which are then utilised as a part of multiple physiological processes including redox defence. During the methionine cycle, the vitamin B12-dependent enzyme methionine synthetase converts homocysteine to methionine. The enzyme S-adenosylmethionine (SAM) synthetase then uses methionine in the production of the reactive methyl carrier SAM. SAM-binding methyltransferases then utilise SAM as a cofactor to methylate proteins, small molecules, lipids, and nucleic acids. RESULTS: We describe a novel SAM methyltransferase, RIPS-1, which was the single gene identified from forward genetic screens in Caenorhabditis elegans looking for resistance to lethal concentrations of the thiol-reducing agent dithiothreitol (DTT). As well as RIPS-1 mutation, we show that in wild-type worms, DTT toxicity can be overcome by modulating vitamin B12 levels, either by using growth media and/or bacterial food that provide higher levels of vitamin B12 or by vitamin B12 supplementation. We show that active methionine synthetase is required for vitamin B12-mediated DTT resistance in wild types but is not required for resistance resulting from RIPS-1 mutation and that susceptibility to DTT is partially suppressed by methionine supplementation. A targeted RNAi modifier screen identified the mitochondrial enzyme methylmalonyl-CoA epimerase as a strong genetic enhancer of DTT resistance in a RIPS-1 mutant. We show that RIPS-1 is expressed in the intestinal and hypodermal tissues of the nematode and that treating with DTT, ß-mercaptoethanol, or hydrogen sulfide induces RIPS-1 expression. We demonstrate that RIPS-1 expression is controlled by the hypoxia-inducible factor pathway and that homologues of RIPS-1 are found in a small subset of eukaryotes and bacteria, many of which can adapt to fluctuations in environmental oxygen levels. CONCLUSIONS: This work highlights the central importance of dietary vitamin B12 in normal metabolic processes in C. elegans, defines a new role for this vitamin in countering reductive stress, and identifies RIPS-1 as a novel methyltransferase in the methionine cycle.

StLTO1, a lumen thiol oxidoreductase in Solanum tuberosum L., enhances the cold resistance of potato plants.

Cold stress reduces plant photosynthesis and increases the accumulation of reactive oxygen species (ROS) in plants, thereby dramatically affecting plant growth, crop productivity and quality. Here, we report that lumen thiol oxidoreductase 1 (StLTO1), a vitamin K epoxide reductase (VKOR)-like protein in the thylakoid membrane of Solanum tuberosum L., enhances the cold tolerance of potato plants. Under normal conditions, overexpression of StLTO1 in plants promoted plant growth. In addition, potato plants overexpressing StLTO1 displayed enhanced photosynthetic capacity and increased capacity for scavenging ROS compared to StLTO1 knockdown and wild-type potato plants under cold conditions. Overexpression of StLTO1 in potato plants also improved cold-regulated (COR) gene expression after cold stress. Our results suggest that StLTO1 acts as a positive regulator of cold resistance in potato plants.

Study of the Association between Thiols and Oxidative Stress Markers in Children with Obesity.

Obesity has reached epidemic proportions, and the World Health Organization defined childhood overweight and obesity as a noncommunicable disease that represents the most serious public health challenges of the twenty-first century. Oxidative stress, defined as an imbalance between oxidants and antioxidants causing an impairment of the redox signals, is linked to the development of metabolic diseases. In addition, reactive oxygen species generated during metabolic disorder could increase inflammation, causing the development of insulin resistance, diabetes, and cardiovascular disease. We analyze serum levels of cysteine (Cys), cysteinyl-glycine (Cys-Gly), homocysteine (Hcy), and glutathione (GSH), and other markers of oxidative stress, such as thiobarbituric acid reactive substances (T-BARS), 8-isoprostane, and protein carbonyl in our children with obesity. Total antioxidant status was also determined. We found lower GSH and Cys-Gly levels, and higher Hcy and oxidative stress markers levels. We also found a positive correlation between Body Mass Index (BMI), Cys, GSH, and Hcy levels, between insulin and Cys levels, and between BMI and the homeostasis model assessment-estimated insulin resistance (HOMA-IR) with 8-isoprostane levels. Finally, we found a correlation between age and GSH and Cys levels. The deficiency of GSH could be restored by dietary supplementation with GSH precursors, supplying an inexpensive approach to oppose oxidative stress, thus avoiding obesity complications.

Protective Effect of Portulaca oleracea on Streptozotocin-Induced Type I Diabetes-Associated Reproductive System Dysfunction and Inflammation.

BACKGROUND: Type-one diabetes (T1D), a chronic autoimmune disease with marked inflammatory responses, is associated with infertility complications and implications. Based on the anti-diabetic, antioxidant, and anti-hyperlipidemic potential of Portulaca oleracea (PO), this study aimed to evaluate the protective effect of this plant extract on streptozotocin-induced type-I-diabetes-associated reproductive system dysfunction and inflammation. METHODS: Male rats were randomly divided into four experimental groups: control, diabetic, and treatment/s (PO extract at 100 or 300 mg/kg/daily). Then food and water consumption, body, testis and epididymis weights, histopathological evaluation, seminiferous tubules diameter, sperm count and motility, glucose levels, sex hormones, and inflammatory and oxidative stress markers were evaluated. RESULTS: Our results showed that streptozotocin-induced diabetes significantly increased food and water consumption; increased glucose, MDA, TGF-ß1, and TNF-α levels; and decreased the seminiferous tubules diameter, sperm count and motility, levels of LH, testosterone, total thiol, VEGF, and SOD activity. Interestingly, PO extract (phytochemically characterized by using liquid chromatography-mass spectrometry to detect bioactive molecules) significantly ameliorated these parameters and histopathological indexes' damage in rats. CONCLUSION: Even if more preclinical assessments are needed to better characterize the mechanism/s of action, the results of this study will pave the way for the rational use of PO on diabetic-associated clinical complications and implications.

The effect of riboflavin supplementation on the systemic redox status in healthy volunteers: A post-hoc analysis of the RIBOGUT trial.

BACKGROUND: Riboflavin is a redox-active vitamin that plays a pivotal role in human energy metabolism. Riboflavin may have beneficial health effects by increasing extracellular antioxidant capacity, thereby alleviating oxidative stress. Reduced levels of free thiols in blood reflect systemic oxidative stress, since they are readily oxidized by reactive species. In this study, we aimed to study the potential of riboflavin supplementation to improve the systemic redox status in healthy volunteers. METHODS: This study was a post-hoc analysis of the RIBOGUT study, a randomized, double-blind, placebo-controlled human intervention trial that investigated the effect of riboflavin supplements on the gut microbiota composition of healthy individuals. Serum free thiols were quantified before and after intervention and adjusted to serum albumin levels. Changes in albumin-adjusted free thiols were analyzed, as well as potential associations with routine laboratory parameters and faecal bacterial quantification by fluorescence in-situ hybridization (FISH). RESULTS: Participants were randomized to either placebo (n = 34), riboflavin 50 mg daily (n = 32), or riboflavin 100 mg daily (n = 33). At baseline, no significant differences in albumin-adjusted serum free thiols were observed. After intervention with either placebo or riboflavin, albumin-adjusted serum free thiols did not significantly change (P > 0.05), however, observed changes were inversely associated with changes in C-reactive protein (CRP) levels (r = -0.22, P < 0.05). At baseline, albumin-adjusted serum free thiols were positively associated with faecal relative abundances of Faecalibacterium prausnitzii (P < 0.01). CONCLUSION: Riboflavin did not change the systemic redox status in healthy individuals as reflected by serum free thiols, but observed changes in albumin-adjusted free thiol levels were negatively associated with changes in CRP levels. Strikingly, albumin-adjusted free thiols were independently associated with relative abundances of faecal F. prausnitzii, which may suggest a potential host redox-microbiota interaction.

The Cd sequestration effects of rice roots affected by different Si management in Cd-contaminated paddy soil.

The application of exogenous silicon (Si) reportedly is one of the eco-friendly practices to mitigate cadmium (Cd) phytotoxicity and regulate the chemical behaviors of Cd in the soil-rice system. But the efficiency of Si on the Cd retention by rice root varies with the Si fertilizer management. The objective of this paper was to interpret the differences in Cd immobilization by rice roots and relevant mechanisms under different ways of Si application (T-Si, supplied at transplanting stage; TJ-Si, split at transplanting and jointing stage with the ratio of 50 % to 50 %; J-Si, supplied at jointing stage and CK, none of Si application) in Cd-contaminated paddy soils. The results showed that the Cd-retention capacity of rice root was increased by 0.60 % ~ 3.06 % under different Si management when compared to CK. The concentrations of monosilicic acid in soils and in apoplast and symplast of roots were increased significantly by Si application, while Cd concentrations in apoplast and symplast of root were decreased by 28.50 % (T-Si), 40.64 % (TJ-Si) and 30.26 % (J-Si), respectively. The distribution of Cd in rice cell wall was increased significantly by TJ-Si. The Cd concentrations of inert fractions (F3, F4 and F6) in root of TJ-Si were raised obviously. Si application downregulated the expression of OsIRT2 and OsNramp5 while upregulated OsHMA3, and the expression of OsHMA3 treated by TJ-Si was obviously higher than CK and J-Si. The distributions of the passive Cd in roots bound with thiol compounds (NPT, GSH and PCs) and polysaccharide components (pectin, hemicelluloses 1 and hemicellulose 2) were raised much more by TJ-Si than by T-Si and J-Si. On the whole, compared with T-Si and J-Si, TJ-Si could more easily replenish soil available Si and enhance Cd sequestration in roots as the result of the decrease of Cd transport factor in roots. This study unravels some mechanisms about different Si management on increasing Cd retention and decreasing Cd migration in rice roots, and TJ-Si is worthy of being recommended.

Food additive sodium bisulfite induces intracellular imbalance of biothiols levels in NCM460 colonic cells to trigger intestinal inflammation in mice.

Sulfites and other preservatives are considered food additives to prevent pathogen growth in food, and they are generally regarded as safe since the late 1950s. However, the possible effects of sulfites on potential damage to host intestinal tissue remain largely unexplored. Given that endogenous sulfite mainly comes from the metabolism of biothiol, we attempted to clarify the relationship among biothiol levels, gut and food additives sulfite, including sodium bisulfite (NaHSO3), and the possible mechanism of sulfite affecting the intestine. In the present study, the NaHSO3 treatments markedly increased the homocysteine (Hcy) level but decreased the cysteine (Cys) level by promoting the expression of Hcy synthase and inhibiting the activities of cystathionine ß-synthase and cystathionine γ-lyase in NCM460 cells. The level of methionine (Met) was not significantly changed, but NaHSO3 promoted ROS-mediated NF-κB signaling pathway, and increased the expressions of proinflammatory cytokines by regulating the levels of Hcy and Cys in NCM460 cells. Vitamin B6 (VB6) supplementation successfully ameliorated NaHSO3-induced damage in NCM460 cells and the colon of Balb/c mice. Altogether, our study provided valuable insights into the safety evaluation of food preservatives. Besides, VB6 could be used as a promising candidate in novel therapies for sodium bisulfite-induced intestinal inflammation.

Active O-acetylserine-(thiol) lyase A and B confer improved selenium resistance and degrade l-Cys and l-SeCys in Arabidopsis.

The roles of cytosolic O-acetylserine-(thiol)-lyase A (OASTLA), chloroplastic OASTLB, and mitochondrial OASTLC in plant selenate resistance were studied in Arabidopsis. Impairment in OASTLA and OASTLB resulted in reduced biomass, chlorophyll and soluble protein content compared with selenate-treated OASTLC-impaired and wild-type plants. The generally lower total selenium (Se), protein-Se, organic-sulfur and protein-sulfur (S) content in oastlA and oastlB compared with wild-type and oastlC leaves indicated that Se accumulation was not the main cause for the stress symptoms in these mutants. Notably, the application of selenate positively induced S-starvation markers and the OASTLs, followed by increased sulfite reductase, sulfite oxidase activities, and increased sulfite and sulfide concentrations. Taken together, our results indicate a futile anabolic S-starvation response that resulted in lower glutathione and increased oxidative stress symptoms in oastlA and oastlB mutants. In-gel assays of l-cysteine and l-seleno-cysteine, desulfhydrase activities revealed that two of the three OASTL activity bands in each of the oastl single mutants were enhanced in response to selenate, whereas the impaired proteins exhibited a missing activity band. The absence of differently migrated activity bands in each of the three oastl mutants indicates that these OASTLs are major components of desulfhydrase activity, degrading l-cysteine and l-seleno-cysteine in Arabidopsis.

The effect of Cinnamomum cassia extract on oxidative stress in the liver and kidney of STZ-induced diabetic rats.

OBJECTIVES: Many diabetes-related complications are caused by oxidative stress. In the current study, the protective effect of Cinnamomum cassia against diabetes-induced liver and kidney oxidative stress was evaluated. METHODS: The male Wistar rats (n=48) were randomly divided into six groups including; control group received 500 µL normal saline orally for 42 days. Diabetes groups received intraperitoneally (i.p.) streptozotocin (STZ) as single-dose (60 mg/kg, i.p.). Cinnamon extract (100, 200, 400 mg/kg) and metformin (300 mg/kg) were orally administered to diabetic rats for 42 days. After the experiment period, the animals were anesthetized and the liver and kidney tissues were quickly removed and restored for oxidative stress evaluation. The levels of malondialdehyde (MDA), total thiol content, glutathione (GSH), nitric oxide (NO) metabolites, as well as, superoxide dismutase (SOD) and catalase (CAT) activities were measured in kidney and liver tissue. RESULTS: The level of MDA, SOD, and CAT activities increased significantly, while the total thiol content, and NO production were significantly reduced in diabetic animals compared to the control group (from p<0.05 to p<0.001). Treatment with cinnamon extract significantly decreased the MDA level, as well as, SOD and CAT activities in the liver and kidney of diabetic rats (from p<0.05 to p<0.001). In the liver and kidney of cinnamon treated groups, GSH and total thiol contents and NO production were significantly higher than diabetic group (from p<0.05 to p<0.001). CONCLUSIONS: Cinnamon extract due to its potent antioxidant property could be effective in decrease of diabetes-induced oxidative stress that plays a major role in renal and hepatic complications.

Gastroprotective action of the ethanol extract of Leonurus sibiricus L. (Lamiaceae) in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus sibiricus L. (Lamiaceae) is a medicinal plant known in Brazil as "rubim" or "erva de macaé". It is used for various purposes, including stomach disorders. AIM OF THE STUDY: To evaluate the effect of the ethanol extract of the aerial parts of L. sibiricus (EELs) in models of gastric damage in mice. MATERIAL AND METHODS: The effect of EELs (50, 100 and 300 mg/kg, p.o., 1 h before induction) was tested on acidified ethanol (ACEt)-induced gastric ulcers. Additionally, we tested the effect of EELs (by intraduodenal administration) in the pylorus ligation (PL) model. RESULTS: Pretreatment with EELs, at 300 mg/kg, but not 50 and 100 mg/kg, reduced the relative area of gastric ulcers induced by ACEt (p < 0.01) and lipoperoxidation (p < 0.001), and increased the sulfhydryl content (p < 0.01) in the stomach in comparison with the vehicle group. Pretreatment with N-ethylmaleimide (a blocker of non-protein sulfhydryl groups, 10 mg/kg, i.p.) or glibenclamide (a KATP channel blocker, 10 mg/kg, i.p.) inhibited the gastroprotective response caused by EELs (300 mg/kg; p < 0.001), but there were no alterations due to pretreatments with inhibitors of the synthesis of prostaglandins (indomethacin, 10 mg/kg), nitric oxide (L-NAME, 70 mg/kg) or hydrogen sulfide (DL-propargylglycine, 10 mg/kg). Treatment with EELs (300 mg/kg) reduced mucus production (p < 0.001) and the volume of gastric secretion (p < 0.001) after PL without affecting gastric acidity or pH. CONCLUSIONS: These results provide evidence that EELs exerts gastroprotective action in mice, with the participation of oxidative stress and mediation of NP-SH, KATP channels and mucus production.

Selenium alleviates arsenic induced stress by modulating growth, oxidative stress, antioxidant defense and thiol metabolism in rice seedlings.

This study aims to investigate the potentiality of selenium in modulating arsenic stress in rice seedlings. Arsenate accumulation along with its transformation to arsenite was enhanced in arsenate exposed seedlings. Arsenite induced oxidative stress and severely affected the growth of the seedlings. Arsenate exposure caused an elevation in ascorbate and glutathione levels along with the activities of their metabolizing enzymes viz., ascorbate peroxidase, glutathione reductase, glutathione-S-transferase, and glutathione peroxidase. Phytochelatins content was increased under arsenic stress to subdue the toxic effects in the test seedlings. Co-application of arsenate and selenate in rice seedlings manifested pronounced alteration of oxidative stress, antioxidant defense, and thiol metabolism as compared to arsenate treatment only. ANOVA analysis (Tukey's HSD test) demonstrated the relevance of using selenate along with arsenate to maintain the normal growth and development of rice seedlings. Thus, exogenous supplementation of selenium will be a beneficial approach to cultivate rice seedlings in arsenic polluted soil.

Arsenic toxicity in the environment is a global concern, causes chronic signs of poisoning to plants and humans, leads to ecological imbalance. Selenium is known for its antagonistic characteristics and has been found to be effective in combating the adversities of arsenic at low concentrations (5 µM). The present study was performed to explore the comparative responses of rice seedlings during the joint application of selenium and arsenic in terms of growth, generation of oxidative stress, antioxidant defense, and thiol metabolism. Although the molecular basis of arsenic­selenium interaction is widely known a small number of reports were listed about the physio-chemical role of selenium against arsenic stress. Thus, we investigated the influence of selenium to alleviate arsenic-induced toxic effects by modulating the activities of antioxidant enzymes and reducing the levels of oxidative stress markers. It has been noted that selenium regulates thiol metabolism which is known to play a key role in growth preservation by restriction of arsenic translocation. The outcome from the study would be useful in field trials for sustainable agriculture in arsenic-contaminated soil.

Dietary inclusions of Solanum vegetables mitigate aluminum-induced redox and inflammation-related neurotoxicity in Drosophila melanogaster model.

BACKGROUND: This study investigated the modulatory capacity of two Solanum green leafy vegetables; S. macrocarpon L. (African eggplant AE) and S. nigrum L. (Black nightshade BN) on dysregulation of some antioxidant, pro-apoptotic, pro-inflammatory-like, acetylcholinesterase gene expression and redox status in the Drosophila melanogaster model of aluminum-induced neurotoxicity. METHODS: Flies were exposed to AlCl3 (6.7 mM) alone or in combination with the leaves (0.1 and 1.0%) from both samples in their diet for seven days. Thereafter, the fly heads were rapidly separated, homogenized, and used to assay for reactive oxygen species (ROS), total thiol content, catalase, glutathione-S-transferase (GST), acetylcholinesterase (AChE) activities, and the expression of antioxidant-mediators (Hsp70, catalase, cnc/Nrf2, Jafrac1 and FOXO), acetylcholinesterase (Ace1), pro-apoptotic caspase-like (Dronc) and its regulator (reaper), as well as inflammation-related (NF-kB/Relish) genes. RESULTS: Results showed that AlCl3-exposed flies had significantly reduced survival rate which were ameliorated by AlCl3 also elevated ROS, GST and reduced AChE activities in fly heads while dietary inclusions of AE and BN ameliorated survial rate and oxidative stress in AlCl3-exposed flies. In addition, Hsp70, Jafrac1, reaper and NF-kҝB/Relish were significantly upregulated in AlCl3-exposed fly heads, while cnc/Nrf2 and FOXO were significantly downregulated, but catalase, Dronc and Ace were, not significantly modulated. Nevertheless, these impairments in gene expression levels were ameliorated by dietary inclusions of AE and BN during AlCl3 exposure. CONCLUSION: These findings showed that dietary inclusions of AE and BN leaves offer protection against Al-induced neurotoxicity in D. melanogaster and thus, could serve as functional foods with neuroprotective properties.

Dietary thiols accelerate aging of C. elegans.

Glutathione (GSH) is the most abundant cellular antioxidant. As reactive oxygen species (ROS) are widely believed to promote aging and age-related diseases, and antioxidants can neutralize ROS, it follows that GSH and its precursor, N-acetyl cysteine (NAC), are among the most popular dietary supplements. However, the long- term effects of GSH or NAC on healthy animals have not been thoroughly investigated. We employed C. elegans to demonstrate that chronic administration of GSH or NAC to young or aged animals perturbs global gene expression, inhibits skn-1-mediated transcription, and accelerates aging. In contrast, limiting the consumption of dietary thiols, including those naturally derived from the microbiota, extended lifespan. Pharmacological GSH restriction activates the unfolded protein response and increases proteotoxic stress resistance in worms and human cells. It is thus advantageous for healthy individuals to avoid excessive dietary antioxidants and, instead, rely on intrinsic GSH biosynthesis, which is fine-tuned to match the cellular redox status and to promote homeostatic ROS signaling.

Dietary supplementation with increasing doses of an organic micromineral complex on juvenile Nile tilapia: Effects on the antioxidant defense system and tissue deposition.

The effect of increasing amounts (0%, 25%, 50%, 75%, and 100%) of dietary supplementation with an organic micromineral complex (Fe, Zn, Cu, Mn, and Se) on antioxidant defenses and mineral deposition in tissues of Nile tilapia juveniles was evaluated, where 100% supplementation represented the average adopted by the feed industry in Brazil. Fish (initial weight 23.93 ± 0.80 g) were fed until apparent satiation twice a day for 56 days. The maximum deposition of Fe and Zn in the hepatopancreas occurred in fish given approximately 50% supplementation, whereas the deposition of Mn and Se increased linearly with the inclusion of the complex. The activity of catalase and superoxide dismutase in the hepatopancreas decreased in fish fed the 50% dose, when compared to those not receiving mineral supplementation or those receiving higher doses. Glutathione peroxidase (GPx) activity in the hepatopancreas increased as the dietary Se concentration increased. However, the concentration of metallothionein in the hepatopancreas showed an inverse relationship to the increase in dietary supplementation of the organic mineral complex. There was no relationship between the doses of organic micromineral supplementation and the activities of GPx, reduced glutathione, non-protein thiols, or protein carbonylation. However, diets supplemented with 50% to 100% promoted greater GPx activity when compared to the 0% supplemented diet. Supplementation with intermediate doses of organic microminerals, approximately 50% of that used in commercial tilapia diets, promoted the homeostasis of metal metabolism, especially for Fe and Zn.

Changes in Biothiol Levels Are Closely Associated with Alzheimer's Disease.

BACKGROUND: Serum homocysteine (Hcy) level is considered to be an important biomarker for Alzheimer's disease (AD); however, the status of Hcy in brain tissue, and the association between brain and serum levels of Hcy in AD patients remain unclear. OBJECTIVE: We aimed to examine whether the changes of three thiols are consistent in serum of AD patients and the brain of APP/PS1 mice, and to verify the effectiveness of Hcy as a biomarker for early AD detection. METHODS: The levels of Hcy, cysteine (Cys), and glutathione (GSH) in Aß1-42-treated PC12 cells, the brain and hippocampus of APP/PS1 mouse, and the serum of AD patients were evaluated using ethyl (E)-3-(9-chloro-11-oxo-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f] pyrido [3,2,1 -ij] quinolin-10-yl)-2-cyanoacrylate (Probe 1) and ELISA assay or LC-MS. RESULTS: Measurement by Probe 1 revealed a significant increase in Hcy level, and a decrease in Cys and GSH levels in Aß1-42-treated PC12 cells and the serum of AD patients. The hippocampus and whole brain of APP/PS1 mice also showed a significant increase in Hcy level alongside the accumulation of age-related AD symptoms. The upregulation of Hcy and the downregulation of Cys and GSH were reversed in the Aß1-42-treated PC12 cells and the brain of APP/PS1 mice when supplemented with VB6. CONCLUSION: Changes in Hcy, Cys, and GSH levels in the brain of APP/PS1 mice and Aß1-42-treated PC12 cells were observed in situ with a new fluorescent probe, which were consistent with the abnormal changes in Hcy, Cys, and GSH levels in the serum of AD patients. VB6 supplementation was successful in ameliorating abnormal increases in Hcy levels.