Decrease In GSH Content Research Articles

Effect of total flavonoids of Spatholobus suberectus Dunn on PCV2 induced oxidative stress in RAW264.7 cells

BackgroundThis study was carried out to investigate the effect of total flavonoids of Spatholobus suberectus Dunn (TFSD) on PCV2 induced oxidative stress in RAW264.7 cells.MethodsOxidative stress model was established in RAW264.7 cells by infecting with PCV2. Virus infected cells were then treated with various concentrations (25 mg/ml, 50 mg/ml and 100 mg/ml) of TFSD. The levels of oxidative stress related molecules (NO, ROS, GSH and GSSG) and activities of associated enzymes (SOD, MPO and XOD were analyzed using ultraviolet spectrophotometry, fluorescence method and commercialized detection kits.ResultsPCV2 infection induced significant increase of NO secretion, ROS generation, GSSG content, activities of both XOD and MPO, and dramatically decrease of GSH content and SOD activity in RAW264.7 cells (P < 0.05). After treating with TFSD, PCV2 induced alteration of oxidative stress related molecule levels and enzyme activities were recovered to a level similar to control.ConclusionOur findings indicated that TFSD was able to regulate oxidative stress induced by PCV2 infection in RAW264.7 cells, which supports the ethnomedicinal use of this herb as an alternative or complementary therapeutic drug for reactive oxygen-associated pathologies.

The effects of anthracene on biochemical responses of Mediterranean mussels Mytilus galloprovincialis

ABSTRACTMediterranean mussels Mytilus galloprovincialis is among the most widely used bioindicators, and anthracene (AN) is one of the most commonly found hydrocarbons in the aquatic environment. M. galloprovincialis were exposed to nominal concentrations of 0.05, 0.15 and 0.4 μg/L AN. Chemical analysis using high-performance liquid chromatography revealed the uptake of AN in the whole soft body and digestive gland at different amounts. After a short exposure (2, 4 and 8 days), the results revealed that AN induced malondialdehyde (MDA), glutathione (GSH) and acetylcholinesterase (AChE) activity in digestive gland. Our findings demonstrated also that AN reduced the filtration rates in a concentration-dependent manner. Increase in lipid peroxidation (MDA content) in digestive gland (p < .05) can possibly indicate that AN can cross the membrane barrier, leading to cellular membrane alteration. Decrease in GSH content following the concentration and exposure time support MDA content result. AN exposure significantly reduced AChE activity as a more sensitive biomarker in digestive gland in a time- and concentration-dependent manner. This review provides a framework for the understanding of toxicological effects of AN under an environmental point of view. It provides also original data on the distribution of AN in M. galloprovincialis, where digestive gland constitutes a valuable organ for investigating AN biotransformation and toxicity.

Role of Bone Marrow Transplantation in Reducing the Dangerous Effect of Multi-Walled Carbon Nanotubes or / and Gamma Rays on Male Rats

Aim of the work: this study evaluated the efficacy of bone marrow (BM) transplantation to protect male rats from dangerous effect of multi-walled carbon nanotubes (MWCNTs) or/and γ-irradiation on the hematopoietic and lung tissues. Materials and methods: experimental animals were divided into 8 groups each consist of 6 male albino rats. Control group, BM-injected group, MWCNTs-injected group, 5Gy γ-irradiated group, 5Gy γ-irradiated+ MWCNTs-injected group, MWCNTs-injected+ BM-injected group, 5Gy γ-irradiated+ BM-injected group and 5Gy of γ-irradiated+ MWCNTs-injected + BM-injected group. All the treated animal groups were sacrificed after 28 days of the treatments. Blood components, MDA and GSH levels in the lung tissue were analyzed. The histopathological study in the lung tissue was also recorded. Results: exposure to MWCNTs or/and γ-radiation induced a significant decrease in certain blood components (WBCs, RBCs, Hb content, HCT value and PLT count). Furthermore, a significant elevation in MDA level and a significant decrease in GSH content were detected in the lung tissue. The histopathological changes after exposure of rats to MWCNTs recorded perivasculitis, atelectasis and interstitial pneumonia. Also, γ-radiation represented more collapsed and thickened walls in the alveoli, thickened bronchiolar walls with partial epithelial lining and foci of pulmonary hemorrhage in the lung tissue. The effect of BM transplantation after MWCNTs or/and γ-radiation ameliorated the values of blood components, MDA and GSH levels in the lung tissue. The improvement occurred by BM transplantation in rats treated with MWCNTs or/and exposed to γ-radiation were also recorded. The lung tissue showed numerous alveoli with thin interalveolar septa, alveolar sacs and terminal bronchioles with highly folded mucosa. Conclusion: treatment with BM transplantation improved the most deleterious parameters obtained in the blood and lung tissue of MWCNTs exposed or/and γ-irradiated rats.

Moderate selenium dosing inhibited chromium (VI) toxicity in chicken liver.

This study aimed to clarify the effect of selenium (Se) on chromium (VI) [Cr(VI)]-induced damage in chicken liver. A total of 105 chickens were randomly divided into seven groups of 15. Group I received deionized water; group II received Cr(VI) (7.83mg/kg/d) alone; and other groups orally received both Cr(VI) (7.83mg/kg/d) and Se of different doses (0.14, 0.29, 0.57, 1.14, and 2.28mg/kg/d). The levels of superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), Ca2+ -ATPase, and mitochondrial membrane potential (MMP) were measured. Results showed that Cr(VI) increased MDA content and decreased GSH content, T-SOD activity, Ca2+ -ATPase activity, and MMP level. Meanwhile, Se co-treatment (0.14, 0.29, and 0.57mg/kg/d) increased the viability of the above indicators compared with Cr(VI)-treatment alone. In addition, histopathologic examination revealed that Cr(VI) can cause liver damage, whereas Se supplementation of moderate dose inhibited this damage. This study confirmed that Se exerted protective effect against Cr(VI)-induced liver damage.

Glutathione metabolism in the prefrontal brain of adults with high-functioning autism spectrum disorder: an MRS study

BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disease characterized by difficulties in social communication, unusually restricted, repetitive behavior and interests, and specific abnormalities in language and perception. The precise etiology of ASD is still unknown and probably heterogeneous. In a subgroup of patients, toxic environmental exposure might lead to an imbalance between oxidative stress and anti-oxidant systems. Previous serum and postmortem studies measuring levels of glutathione (GSH), the main cellular free radical scavenger in the brain, have supported the hypothesis that this compound might play a role in the pathophysiology of autism.MethodsUsing the method of single-voxel proton magnetic resonance spectroscopy (MRS), we analyzed the GSH signal in the dorsal anterior cingulate cortex (dACC) and the dorsolateral prefrontal cortex (DLPFC) of 24 ASD patients with normal or above average IQs and 18 matched control subjects. We hypothesized that we would find decreased GSH concentrations in both regions.ResultsWe did not find overall group differences in neurometabolites including GSH, neither in the dorsal ACC (Wilks’ lambda test; p = 0.429) nor in the DLPFC (p = 0.288). In the dACC, we found a trend for decreased GSH signals in ASD patients (p = 0.076).ConclusionsWe were unable to confirm our working hypothesis regarding decreased GSH concentrations in the ASD group. Further studies combining MRS, serum, and cerebrospinal fluid measurements of GSH metabolism including other regions of interest or even whole brain spectroscopy are needed.

Protective effects of melatonin on the activity of SOD, CAT, GSH-Px and GSH content in organs of mice after administration of SNP.

Sodium nitroprusside (SNP) is an antihypertensive drug with proven dose-dependent toxic effects attributed mainly to the production of cyanide but also excesive nitric oxide (NO) and derived reactive species. The present study evaluated whether melatonin administration would have time-dependent protective effect against SNP−induced toxicity. Male Swiss mice were used in this study. Control mice were treated with 0.9% NaCl; the second group was injected with 10 mg melatonin (MEL)/kg body weight (b.w.); the third group was given SNP at the dose of 3,6 mg/kg b.w.; the fourth group received both MEL and SNP at the same doses. In homogenates of brain, liver and kidneys, activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were estimated after 3, 6 and 24 h of drugs administration. The concentration of reduced glutathione (GSH) was also evaluated in the blood, brain, liver and kidneys of mice at the same time intervals. In animals receiving MEL, the highest levels of GSH were observed in all the organs as compared to the control after 3, 6 h. Meanwhile, SNP decreased GSH concentration in the blood, brain, liver and kidneys in all time intervals. Administration of MEL in combination with SNP increased the GSH levels in all organs, as compared to the administration of SNP alone; this effect was observed after 3, 6 and 24 h. The activity of SOD, CAT and GSH-Px in the MEL-treated group increased after 3 h in all the organs, while in liver and kidney the increase was also observed after 6 h. Conversely, the SNP intoxication caused a decrease of the activity of enzymes in the tested organs in all intervals, while administration of MEL + SNP resulted in increased activities of SOD, CAT and GSH-Px in all the organs after 3 h and 6 h. The investigation carried out in the present study provide new data to add to the study of antioxidant properties of MEL and SNP-induced oxidative stress with regard to time-dependent properties in different types of tissues.

Nrf2 mediates redox adaptation in NOX4-overexpressed non-small cell lung cancer cells

The redox adaptation mechanisms in cancer cells are very complex and remain largely unclear. Our previous studies have confirmed that NADPH oxidase 4 (NOX4) is abundantly expressed in non-small cell lung cancer (NSCLC) and confers apoptosis resistance on NSCLC cells. However, the comprehensive mechanisms for NOX4-mediated oxidative resistance of cancer cells remain still undentified. The present study found that NOX4-derived H2O2 enhanced the nuclear factor erythroid 2-related factor 2 (Nrf2) stability via disruption of redox-dependent proteasomal degradation and stimulated its activity through activation of PI3K signaling. Specifically, the results showed that ectopic NOX4 expression did not induce apoptosis of A549 cells; however, inhibition of Nrf2 resulted in obvious apoptotic death of NOX4-overexpressed A549 cells, accompanied by a significant increase in H2O2 level and decrease in GSH content. Besides, inhibition of Nrf2 could suppress cell growth and efficiently reverse the enhancement effect of NOX4 on cell growth. The in vivo data confirmed that inhibition of Nrf2 could interfere apoptosis resistance in NOX4-overexpressed A549 tumors and led to cell growth inhibition. In conclusion, these results reveal that Nrf2 is critically involved in redox adaptation regulation in NOX4-overexpressed NSCLC cells. Therefore, NOX4 and Nrf2 may be promising combination targets against malignant progression of NSCLC.

Impact of alcohol on hepatic mitochondrial DNA damage in streptozotocin diabetic rats

Mitochondrial dysfunction with increased production of reactive oxygen species (ROS) is a characteristic feature of diabetes which is associated with damage of mitochondrial DNA (mtDNA). Alcohol metabolism generates ROS with enhanced oxidative stress leading to damage of cellular constituents including mtDNA. The aim of the present study is to investigate the impact of alcohol consumption on hepatic mtDNA damage in diabetic rats. MtDNA was isolated from hepatic tissues of non-diabetic and streptozotocin induced diabetic rats after alcohol treatment. Comprehensive screening of mtDNA displacement loop (D-loop) was carried out by PCR-Sanger’s sequencing analysis. MtDNA deletions were analyzed by long-extension PCR. Furthermore, activities of enzymatic and non-enzymatic antioxidants were measured in hepatic tissue of all rats. Our results showed increased frequency of D-loop mutations in alcoholic-diabetic rats when compared to diabetic or alcoholic non-diabetic rats. DNA mfold analysis predicted higher free energy for 15507C, 15560T and 16116C alleles compared to their corresponding wild alleles which represents less stable secondary structures with negative impact on overall mtDNA function. MtDNA deletions were observed in all experimental groups except controls. Markedly decreased activities of antioxidant enzymes viz., GPx, SOD, catalase and GSH content was identified in alcoholic-diabetic rats when compared to remaining groups. In conclusion, decreased GSH content and lowered activity of catalase, SOD and GPx favor the environment for oxidative stress, which might lead to exacerbation of hepatic mitochondrial DNA damage in diabetic rats receiving alcohol.

Metallothionein protects against isoniazid-induced liver injury through the inhibition of CYP2E1-dependent oxidative and nitrosative impairment in mice

Oxidative stress mediated by hepatic CYP2E1 during isoniazid (INH) metabolism is considered responsible for INH hepatotoxicity. This study attempts to determine whether metallothionein (MT), a cysteine-rich antioxidant can protect against INH-induced liver injury by using a MT-I/II deficient mouse model (MT−/− mice). MT−/− mice and the corresponding wild-type mice received intragastric administrations of 0, 75, 150 and 300 mg/kg of INH for 15 days. The results showed that 150 and 300 mg/kg of INH induced liver injury in both types of mice, as evidenced by increased liver index and histopathological change of liver vacuolar degeneration. Increased hepatic MDA level and 3-NT expression, and decreased GSH content and SOD activity were also observed in both types of mice, indicating the involvement of oxidative and nitrosative stress. INH treatment upregulated hepatic CYP2E1 expression in both types of mice, and the severity of liver injury was in concert with the elevation of CYP2E1 expression. Comparative analyses revealed liver vacuolar degeneration and oxidative and nitrosative stress were more severe in MT−/− mice than wild-type mice, suggesting the hepatoprotection of MT against INH hepatotoxicity. Taken together, these findings clearly demonstrate that MT protects against INH-induced liver toxicity by ameliorating CYP2E1-dependent oxidative and nitrosative impairment.

Effects of faba beans with different concentrations of vicine and convicine on egg production, egg quality and red blood cells in laying hens

The faba bean (Vicia faba L.) is a potential source of proteins for poultry, mainly for laying hens whose protein requirements are lower than those of other birds such as growing broilers and turkeys. However, this feedstuff contains anti-nutritional factors, that is, vicine (V) and convicine (C) that are already known to reduce laying hen performance. The aim of the experiment reported here was to evaluate the effects of a wide range of dietary V and C concentrations in laying hens. Two trials were performed with laying hens fed diets including 20% or 25% of faba bean genotypes highly contrasting in V+C content. In Trial 1, faba beans from two tannin-containing cultivars, but with high or low V+C content were dehulled in order to eliminate the tannin effect. In addition to the contrasting levels of V+C in the two cultivars, two intermediate levels of V+C were obtained by mixing the two cultivars (70/30 and 30/70). In Trial 2, two isogenic zero-tannin faba bean genotypes with high or low V+C content were used. In both trials, a classical corn–soybean diet was also offered to control hens. Each experimental diet was given to 48 laying hens for 140 (Trial 1) or 89 (Trial 2) days. Laying performance and egg quality were measured. The redox sensitivity of red blood cells (RBCs) was assessed by measuring hemolysis and reduced glutathione (GSH) concentration in these cells. Egg weight was significantly reduced by the diets containing the highest concentrations of V+C (P<0.0001) in Trial 1 and slightly reduced (P<0.10) in Trial 2, but only weak linear relationships between egg weight and dietary V+C concentration were established. No negative effect of V+C level was observed for egg quality parameters. In contrast, certain parameters (i.e. Haugh units, yolk color) were improved by feeding low V+C diets (P<0.05). Hemolysis of RBCs was higher in hens fed high V+C diets. A decrease in GSH concentration in RBCs of hens fed the highest levels of V+C was observed. Faba bean genotypes with low concentrations of V+C can therefore be used in laying hen diets up to 25% without any detrimental effects on performance levels or egg characteristics, without any risk of hemolysis of RBCs.

Modulation of Antioxidant Status of Erythrocyte of In Vivo Heat Exposed Rats Fed on Altered Dietary Protein Level

This study was carried out to determine the effect of altered dietary protein level on the antioxidant status of erythrocytes of in vivo heat exposed rats. Experiments were performed on adult (80-90 days old) male Wister strain rats, divided in six groups of five animals each. Animals were exposed to 43±1 °C, ambient humidity conditions for 3 h daily for 15 days in a well maintained climatic chamber. Increased TBARS productions were found when measured in packed erythrocytes and erythrocyte membranes in both the rats fed on 18% or 6% protein diet after acute and chronic heat exposure. Supplementation of ascorbic acid to the rats fed on 18% or 6% protein diet was found to reduce the TBARS production remarkably in packed erythrocytes while it further raised the TBARS production in erythrocyte membrane in response to chronic and acute heat exposure. The liberation of alanine increased in 18% protein-fed as well as 6% protein-fed rats following chronic and acute exposure to heat. Decreased GSH content and increased membrane total thiol (-SH) content of erythrocytes were observed in both 18% protein-fed and 6% protein-fed rats. Prior supplementation of ascorbic acid was found to restore partially the GSH content of erythrocyte and to potentiate the increase in membrane total thiol (–SH) content in both adequately protein-fed and protein-restricted groups of rats.

Ameliorative effect of parsley oil on cisplatin-induced hepato-cardiotoxicity: A biochemical, histopathological, and immunohistochemical study.

Cisplatin (cis-diamminedichloroplatinum, CDDP) is an effective DNA alkylating agent used in the treatment of different types of tumors; however, its clinical use is associated with hepato-cardiotoxicity. The current study was designed to assess the potential protective effect of parsley oil (PO) against CDDP-induced hepato-cardiotoxicity. For this purpose, 25 adult male rats were assigned into five groups, each containing five animals. Group I (control) was administered saline solution. Group II was administered PO at a dosage of 0.42ml/kg BW. Group III were administered CDDP at a dosage of 5mg/kg BW. Group IV was administered PO in addition to CDDP. Group V was administered saline solution in addition to CDDP, after which they were administered PO for five days. Oral administration of either saline solution or PO was performed each day for 10days, while administration of CDDP was via a single intraperitoneal injection five days following the commencement of the experiment. The recorded results revealed that CDDP induced obvious hepatic and cardiac injuries that were indicated by biochemical, histopathological, and immunohistochemical alterations, including elevation of serum hepatic and cardiac injury markers as well as proinflammatory cytokines. Moreover, CDDP induced an increase in the level of hepatic and cardiac injury biomarkers, decreases in the activities of antioxidant enzymes, a decrease in GSH concentration, and an increase in MDA concentration. CDDP also induced histopathological hepatocellular and myocardial changes, and overexpression of p53 and COX-2 in hepatic and cardiac tissues. Administration of PO either as a preventative medicine or as treatment significantly improved all the observed deleterious effects induced by CDDP in rat liver and heart. Thus, it may be concluded that PO, with its antioxidant, anti-inflammatory, and antiapoptotic activities, can potentially be used in the treatment of CDDP-induced hepatic and cardiac injuries.

The effects of silver and arsenic on antioxidant system in Lemna paucicostata: Different effects on glutathione system

Ag+ (AgNO3) and As3+ (As2O3) exposures resulted in dose-dependent decreases in the growth rate of Lemna paucicostata with IC50 values of 0.101±0.004 mg/mL and 0.753±0.127 mg/mL, respectively. Both Ag+ and As3+ caused dose-dependent increases in lipid peroxidation, a key oxidative damage marker. Additionally, Ag+ and As3+ caused increases in some components of antioxidant system, namely, ascorbate content and peroxidase activities such as ascorbate peroxidase, glutathione peroxidase, and guaiacol peroxidase. However, notable differences between Ag+ and As3+ were found in their effects on the glutathione (GSH) system. Ag+ caused significant decreases in the GSH content and activities of glutamate cysteine ligase (GCL) and glutathione reductase (GR), the enzymes involved in the GSH synthesis and redox recycling, respectively. In contrast, As3+ caused increases in the GSH content and GCL activity. Our results suggest that the Ag+-induced decrease in GSH content accompanied by the decreases in its synthesis and redox recycling is a critical component that further predisposes L. paucicostata to Ag+ toxicity.

Exogenous glutathione improves high root-zone temperature tolerance by modulating photosynthesis, antioxidant and osmolytes systems in cucumber seedlings.

To investigate the physiological responses of plants to high root-zone temperature (HT, 35 °C) stress mitigated by exogenous glutathione (GSH), cucumber (Cucumis sativus L.) seedlings were exposed to HT with or without GSH treatment for 4 days and following with 4 days of recovery. Plant physiological variables, growth, and gene expression related to antioxidant enzymes and Calvin cycle were quantified. The results showed that HT significantly decreased GSH content, the ratio of reduced to oxidized glutathione (GSH/GSSG), chlorophyll content, photosynthesis and related gene expression, shoot height, stem diameter, as well as dry weight. The exogenous GSH treatment clearly lessened the HT stress by increasing the above variables. Meanwhile, HT significantly increased soluble protein content, proline and malondialdehyde (MDA) content as well as O2•− production rate, the gene expression and activities of antioxidant enzymes. The GSH treatment remarkably improved soluble protein content, proline content, antioxidant enzymes activities, and antioxidant enzymes related gene expression, and reduced the MDA content and O2•− production rate compared to no GSH treatment in the HT condition. Our results suggest that exogenous GSH enhances cucumber seedling tolerance of HT stress by modulating the photosynthesis, antioxidant and osmolytes systems to improve physiological adaptation.

Artesunate restores spatial learning of rats with hepatic encephalopathy by inhibiting ammonia-induced oxidative damage in neurons and dysfunction of glutamate signaling in astroglial cells.

Artesunate (ART) is an antimalarial drug with potential anti-inflammatory effect. This study aimed to explore the potential protective role of ART in hepatic encephalopathy (HE), involving its function against ammonia toxicity. HE rats were induced by the administration of thioacetamide (TAA, 300mg/kg/day). Spatial learning ability was tested in both Morris water and eight-arm radial maze. Rat cerebellar granule neurons (CGNs) were prepared for ammonia treatment in vitro, in line with SH-SY5Y and C6 cells. ART was administrated at 50 or 100mg/kg/day in vivo or added at 50 or 100μM in vitro. Oxidative damages were evaluated by the changes of cell viability, reactive oxygen species (ROS) levels and glutathione (GSH) content, while glutamate uptake and release, and the activities of glutamine synthetase (GS) and Na+K+-ATPase were measured to indicate the dysfunction of glutamate signaling. Decreased escape latency and increased numbers of working errors were observed in TAA-induced HE rats, which could be significantly restored by ART at a dosage-dependent manner. Decreased cell viability and GSH content and increased ROS accumulation were detected in ammonia-treated SH-SY5Y and CGNs, while ammonia-treated C6 cells showed reduced glutamate uptake, increased glutamate release, and decrease of GSH content, GS and Na+K+-ATPase activity. In contrast, ART, especially at 100μM, strongly reversed all changes induced by ammonia, showing a similar dosage-dependent manner in vitro. This study revealed a new neuroprotective role of ART in the pathogenesis of HE, by protecting neurons and astroglial cells from ammonia-induced damages and dysfunctions.

Exploration of the therapeutic potential effect of Sepia officinalis in animal model of sepsis induced by cecal ligation and puncture

ObjectiveThe present investigation explored the therapeutic potential effect of Sepia officinalis body tissue (SOBT) and Sepia officinalis polysaccharide (SOP) extracts, in animal model of sepsis [induced by cecal ligation and puncture (CLP)]. Materials and methodsExperimental animals were divided into 4 groups, Group 1: Sham control rats. Group 2: Septic rats. Group 3: Septic rats treated with methanolic extract of Sepia officinalis body tissue (SOBT) (500mg/kg body weight) for 2days. Group 4: Septic rats treated with Sepia officinalis polysaccharide (SOP) extract (200mg/kg body weight) for 2days. ResultsThe antioxidant activity of SOBT and SOP was proven by DPPH test. CLP-induced liver and kidney toxicities showed by an increase in the ALAT, ASAT, γGT, ALP, creatinine, BUN and uric acid concentrations in serum. Moreover, CLP-induced oxidative stress in liver and kidney evidenced by the increase of MDA levels, decrease in GSH concentrations and decrease in the enzymatic antioxidants (SOD, CAT, GST). In addition, CLP caused decrease in CYP1A2 content in liver. ConclusionsOur findings demonstrate the therapeutic efficacy of SOBT and SOP in liver and kidney disorders. Therefore this study suggests that SOBT and SOP could be a potential therapeutic agents for sepsis treatment.

Glutathione may have implications in the design of 3-bromopyruvate treatment protocols for both fungal and algal infections as well as multiple myeloma.

In different fungal and algal species, the intracellular concentration of reduced glutathione (GSH) correlates closely with their susceptibility to killing by the small molecule alkylating agent 3-bromopyruvate (3BP). Additionally, in the case of Cryptococcus neoformans cells 3BP exhibits a synergistic effect with buthionine sulfoximine (BSO), a known GSH depletion agent. This effect was observed when 3BP and BSO were used together at concentrations respectively of 4-5 and almost 8 times lower than their Minimal Inhibitory Concentration (MIC). Finally, at different concentrations of 3BP (equal to the half-MIC, MIC and double-MIC in a case of fungi, 1 mM and 2.5 mM for microalgae and 25, 50, 100 μM for human multiple myeloma (MM) cells), a significant decrease in GSH concentration is observed inside microorganisms as well as tumor cells. In contrast to the GSH concentration decrease, the presence of 3BP at concentrations corresponding to sub-MIC values or half maximal inhibitory concentration (IC50) clearly results in increasing the expression of genes encoding enzymes involved in the synthesis of GSH in Cryptococcus neoformans and MM cells. Moreover, as shown for the first time in the MM cell model, the drastic decrease in the ATP level and GSH concentration and the increase in the amount of ROS caused by 3BP ultimately results in cell death.

OXIDATIVE STRESS IN A RAT MODEL OF COTTON SMOKE INHALATION-INDUCED PULMONARY INJURY.

Background:Smoke inhalation injury refers to airway and lung parenchyma injury and general chemical damage caused by inhaling toxic gases and substances. The aim of this study was to explore the oxidative stress mechanism of cotton smoke inhalation-induced pulmonary injury in a rat model.Materials and Methods:Eighteen male Sprague-Dawley rats were randomly divided into control group, 6 h group, and 24 h group (six rats in each group), which duplicated previous rat cotton smoke-inhalation injury models. Rats in 6 h and 24 h groups were euthanised at 6 h and 24 h after smoke inhalation, respectively. ELISA method was used to detect indicators in the rats’ lung tissue. Quantitative iNOS mRNA and γ-GCS mRNA measurements were performed using a fluorescence PCR method.Results:The concentrations of MDA, NO, iNOS, γ-GCS, iNOS mRNA, and the relative expression of γ-GCS mRNA in the rats’ lung tissues in 6 h and 24 h groups were higher than control group (P < 0.05), and the concentration of NO and relative expressions of iNOS mRNA and γ-GCS mRNA in 24 h group were significantly higher than 6 h group (P < 0.05). The concentrations of GSH in 24 h and 6 h groups were significantly lower than control group (P < 0.05), and that in 24 h group was even significantly lower than 6 h group (P < 0.05).Conclusion:In rats with cotton smoke inhalation-induced pulmonary injury, the increased iNOS mRNA transcription can cause increase of iNOS synthesis and promotion of NO synthesis. The increased γ-GCS mRNA transcription can cause increase of γ-GCS synthesis and but decrease of GSH concentration. The activation of the antioxidant system is insufficient to combat oxidative stress damage. So the oxidant/antioxidant system is imbalanced, leading to gradual aggravation of lung injury.

Higher Vulnerability of Menadione-Exposed Cortical Astrocytes of Glutaryl-CoA Dehydrogenase Deficient Mice to Oxidative Stress, Mitochondrial Dysfunction, and Cell Death: Implications for the Neurodegeneration in Glutaric Aciduria Type I.

Patients affected by glutaric aciduria type I (GA-I) show progressive cortical leukoencephalopathy whose pathogenesis is poorly known. In the present work, we exposed cortical astrocytes of wild-type (Gcdh +/+ ) and glutaryl-CoA dehydrogenase knockout (Gcdh -/- ) mice to the oxidative stress inducer menadione and measured mitochondrial bioenergetics, redox homeostasis, and cell viability. Mitochondrial function (MTT and JC1-mitochondrial membrane potential assays), redox homeostasis (DCFH oxidation, nitrate and nitrite production, GSH concentrations and activities of the antioxidant enzymes SOD and GPx), and cell death (propidium iodide incorporation) were evaluated in primary cortical astrocyte cultures of Gcdh +/+ and Gcdh -/- mice unstimulated and stimulated by menadione. We also measured the pro-inflammatory response (TNFα levels, IL1-β and NF-ƙB) in unstimulated astrocytes obtained from these mice. Gcdh -/- mice astrocytes were more vulnerable to menadione-induced oxidative stress (decreased GSH concentrations and altered activities of the antioxidant enzymes), mitochondrial dysfunction (decrease of MTT reduction and JC1 values), and cell death as compared with Gcdh +/+ astrocytes. A higher inflammatory response (TNFα, IL1-β and NF-ƙB) was also observed in Gcdh -/- mice astrocytes. These data indicate a higher susceptibility of Gcdh -/- cortical astrocytes to oxidative stress and mitochondrial dysfunction, probably leading to cell death. It is presumed that these pathomechanisms may contribute to the cortical leukodystrophy observed in GA-I patients.

Cardiac rehabilitation improves the blood plasma properties of cardiac patients.

Cardiac rehabilitation (CR) improves exercise tolerance and general function. However, its effects on blood plasma in cardiac patients remain uncertain. Our aim was to examine the effect of comprehensive CR on the oxidative stress parameters and antioxidant plasma status in patients with coronary artery disease (CAD) after cardiac interventions. Exercise-based rehabilitation was established as ergometer training, adjusted for individual patients' physical efficiency. Training was repeated three times a week for two months. The standard biochemical (total cholesterol, HDL, LDL, triglycerides and erythrocyte sedimentation rate) and metabolic parameters (peak oxygen uptake [VO2] and peak workload) were determined. We assessed plasma viscosity, lipid peroxidation, carbonyl compounds levels, glutathione (GSH) and ascorbate (ASC) levels and the non-enzymatic antioxidant capacity of plasma in 12 patients with CAD before and after CR. Parameters were examined before exercise, immediately after exercise, and 1 h later. We also compared morphological and biochemical parameters of blood, as well as other parameters such as heart rate and blood pressure (resting and exercise), VO2max and peak workload (W) before and after CR. Before CR, a significant decrease in GSH concentration was observed 1 h after exercise. Conversely, after CR, GSH, and ASC levels remained unchanged immediately after exercise. However, ASC increased after CR after exercise and 1 h later in comparison to before CR. There was a significant increase in ferric reduction ability of plasma immediately after exercise after CR, when compared with before CR. CR improved several blood biochemical parameters, peak VO2, induced an increase in systolic blood pressure peak, and patients' peak workload. After CR, improvements were detected in oxidative stress parameters, except in the level of carbonyls. These changes may contribute to the increased functional heart capacity and better tolerance to exercise and functional capacity of the patients. These improvements could indicate better prognosis of future cardiac events and hospitalization and better quality of life.