Plasma Glutathione Concentrations Research Articles

PSLBII-4 The effect of standardized ileal digestible sulfur amino acid intake during late gestation on gilt whole-body nitrogen retention and subsequent litter performance

Abstract Gestating gilts [n = 27; body weight (BW) = 158 ± 5.5 kg] were used to determine the effect of standardized ileal digestible (SID) sulfur amino acid (SAA) intake during late gestation on whole-body nitrogen (N) retention and subsequent litter performance. Gilts were assigned to one of two experimental diets that provided SAA at 60 or 200 % of estimated requirements during late gestation (0.29 and 0.92 % SID SAA, respectively; n = 15 and 12, respectively; Table 1 and 2). Each gilt received 2.53 kg of the assigned diet between gestation d 90 and farrowing; standard lactation and nursery diets were provided to gilts after farrowing and offspring after weaning, respectively. Gilt whole-body N balance was determined between d 107 and 109 of gestation using total urine collection and fecal grab-sampling. After farrowing, litters were standardized to 13 piglets and were not offered creep feed. Whole-body N retention was greater in gilts fed the diet containing 0.92 vs. 0.29 % SID SAA in late gestation (27.2 vs. 19.3 ± 1.8 g/d; P < 0.05; Table 3), but the number of piglets born alive, litter birth weight, subsequent piglet growth rates, and litter size at weaning were not different between treatment groups. The post-weaning growth performance of offspring was also not influenced by maternal dietary treatment in late gestation (Table 4). At farrowing, the post-absorptive plasma concentration of Cys tended to be less (P = 0.072) and taurine was greater (P < 0.01) for gilts fed 0.92 vs. 0.29 % SID SAA in late gestation; however, there were no differences in plasma SAA metabolites concentrations for gilts at weaning or offspring at birth (Table 5. At weaning, offspring from gilts fed 0.92 % SID SAA had greater plasma homocysteine (P < 0.05) and plasma Cys concentrations (tendency; P = 0.072) vs. offspring from gilts fed 0.29 % SID SAA in late gestation. Three weeks after weaning, plasma taurine concentration was less (P < 0.05) for offspring from gilts fed 0.92 vs. 0.29 % SID SAA in late gestation (Table 6). Six weeks after weaning, plasma glutathione concentration tended to be less (P = 0.057) for offspring from gilts fed 0.92 vs 0.29 % SID SAA in late gestation. When SAA were fed below estimated requirements during late gestation, whole-body N retention was reduced, but fetal growth appeared to be maintained, likely at the expense of maternal N retention. Such divergences in dietary SAA supply in late gestation had no effect on subsequent offspring growth performance, but it appeared that offspring SAA metabolism was impacted until at least 6 wk after weaning. The influence of differences in sulfur AA metabolites on offspring performance beyond the nursery phase remains unknown. Therefore, carry-over effects of maternal SAA supply in late gestation should be considered when developing feeding recommendations for gestating gilts.

From balance to imbalance: disruption of plasma glutathione concentration in micropapillary thyroid carcinoma

BackgroundDespite the presence of evidence that establishes a strong correlation between oxidative stress and thyroid cancer, there exists a scarcity of research that investigates the specific role of glutathione as an important antioxidant in this particular context. The objective of this study was to assess the altered balance of oxidative stress in cases of thyroid cancer, which includes both papillary thyroid carcinoma (PTC) and micro PTC (mPTC), by examining and comparing the total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), reduced glutathione (GSH), oxidized glutathione (GSSG), and GSSG/GSH ratio with those of individuals diagnosed with multinodular goiter (MNG) as well as Healthy subjects.Materials and methodsPlasma samples were collected from 92 patients (23 mPTC, 23 PTC, 23 MNG, 23 Healthy). The levels of TAC, TOS, GSH, and GSSG were measured using a commercial assay kits, and the OSI and GSSG/GSH ratio were calculated for each sample. Statistical analyses were performed to compare the oxidative stress between the groups.ResultsThe plasma levels of TOS were significantly higher in the mPTC, PTC, and MNG groups compared to the Healthy individuals (p < 0.05). The OSI in the mPTC and PTC groups showed a significant increase compared to the Healthy group (p < 0.05). The levels of GSH in mPTC and PTC were markedly lower compared to the Healthy subjects (p < 0.01). Interestingly, the concentration of GSH in mPTC was found to be considerably lower than in PTC and MNG patients (p < 0.01).ConclusionThese findings indicate that GSH may be a useful biomarker for evaluating oxidative stress and antioxidant system status in patients with PTC, especially mPTC. Low levels of GSH may indicate increased levels of oxidative stress, which may contribute to the development and progression of mPTC to PTC.

P172: A preliminary study for potential protective role of anti-oxidative stress markers for cognitive impairment: glutathione and glutathione reductase.

Objective:We aimed to study the relationship between glutathione (GSH), a key molecule of the anti-oxidant defense system in the blood, and glutathione reductase (GR), which reduces oxidized GSSG to GSH and maintains redox balance, with the prevalence of Alzheimer’s dementia and cognitive decline.Methods:20 with normal cognition and 20 with Alzheimer's dementia who completed the 3rd f/u clinical evaluation over 6 years were selected by matching age and gender. Plasma glutathione (GSH) and glutathione reductase (GR) concentrations were independent variables. Clinical diagnosis and neurocognitive test scores were used as dependent variables indicating cognitive status.Results:The higher the GR, the greater the possibility of normal cognition rather than Alzheimer's dementia. Also, the higher the GR, the higher the neurocognitive score. However, this association was not significant in GSH in any way. After 6 years, the conversion rate from normal cognition to cognitive impairment was significantly higher in the lower 50th percentile of the GR group than in the upper 50th percentile.Conclusion:According to the result of this study, the higher the GR, the lower the prevalence of Alzheimer's dementia and incidence of cognitive impairment, and the higher the cognitive outcome. Therefore, GR can be regarded as a protective biomarker for Alzheimer’s dementia and cognitive decline.

Potential mechanism for hyperhomocysteinemia in Greyhound dogs.

Greyhounds have been reported to have hyperhomocysteinemia (HHC), but the underlying mechanisms and clinical implications are unclear. Our primary aim was to assess serum concentrations of homocysteine (HCy) and related analytes in Greyhounds and to identify a likely metabolic pathway for HHC. A secondary aim was to determine whether HHC is associated with evidence of oxidative stress. Healthy pet Greyhounds (n = 31) and non-sighthound control dogs (n = 15). Analysis of serum HCy, cobalamin, folate, and methionine, and plasma cysteine, glutathione, and total 8-isoprostane concentrations. Homocysteine concentrations were higher in Greyhounds (median, 25.0 μmol/L) compared to controls (13.9 μmol/L; P < .0001). Cobalamin concentrations were lower in Greyhounds (median, 416 ng/L) compared to controls (644 ng/L; P = .004) and were inversely correlated with HCy (r = -0.40, P = .004). Serum concentrations of folate, which is regenerated when HCy is converted to methionine, also were inversely correlated with HCy (r = -0.47, P = .002). Serum methionine concentrations were more than 4-fold lower in Greyhounds (median, 3.2 μmol/L) compared to controls (median, 15.0 μmol/L), but this difference was not significant (P = .3). Plasma cysteine, glutathione, and 8-isoprostane concentrations did not differ significantly between groups. Our findings suggest a primary defect in conversion of HCy to methionine in Greyhounds, with related impaired folate generation. Ineffective cycling by methionine synthase could lead to secondary cobalamin depletion. Notably, low serum folate and cobalamin concentrations can be observed in Greyhounds without signs of intestinal disease.

Hypoxia and Anoxia Tolerance in Diploid and Triploid Eastern Oysters at High Temperature

Increasing reliance on the use of triploid oysters to support aquaculture production relies on their generally superior growth rate and meat quality over that of diploid oysters. Reports of elevated triploid mortality have generated questions about potential trade-offs between growth and tolerance to environmental stressors. These questions are particularly relevant as climate change, coastal activities, and river management impact water salinity, temperature, nutrients, pH, and oxygen levels within key estuarine oyster growing areas. In particular, the co-occurrence of warm water temperatures and low dissolved oxygen concentration (DO) events are increasingly reported in estuaries, with potentially lethal impacts on sessile, oyster resources. To investigate potential differences in DO tolerance, diploid and triploid market-sized or seed oysters were exposed to continuous normoxia (DO > 5.0 mg L–1), hypoxia (DO < 2.0 mg L–1), and anoxia (DO < 0.5 mg L–1) at 28°C and their mortalities were monitored. The hemolymph of the market-sized oysters was collected to measure cellular and biochemical changes in response to hypoxia and anoxia, whereas their valve movements were also measured. In general, about half of market-sized oysters died within about 1 wk under anoxia (LT50: 5.7–8.9 days) and within about 2 wk under hypoxia (LT50: 11.9–19.4 days) with diploid oysters tending to die faster than triploid oysters. Seed oysters took longer to die than market-sized oysters under both anoxia (LT50: 9.5–12.1 days) and hypoxia (LT50: 21.8–25.0 days) with diploid oysters (LT50: 9.5–11.8 days) dying slightly faster than triploid oysters (LT50: 11.8–12.1 days) under anoxia. Hemolymph pH decreased and plasma calcium and glutathione concentrations increased with decreasing DO, with values under anoxia being different than those under normoxia. Hemocyte density was also lower under anoxia than under either normoxia or hypoxia. Overall, few differences in physiological responses to hypoxia and anoxia were found between diploid and triploid oysters suggesting that ploidy (2N versus 3N) had limited effect on the tolerance and response of eastern oysters to low DO.

Total Flavonoids of Rhizoma Drynariae Mitigates Aflatoxin B1-Induced Liver Toxicity in Chickens via Microbiota-Gut-Liver Axis Interaction Mechanisms.

Aflatoxin B1 (AFB1) is a common mycotoxin that widely occurs in feed and has severe hepatotoxic effects both in humans and animals. Total flavonoids of Rhizoma Drynaria (TFRD), a traditional Chinese medicinal herb, have multiple biological activities and potential hepatoprotective activity. This study investigated the protective effects and potential mechanisms of TFRD against AFB1-induced liver injury. The results revealed that supplementation with TFRD markedly lessened broiler intestinal permeability by increasing the expression of intestinal tight junction proteins, as well as correcting the changes in gut microbiota and liver damage induced by AFB1. Metabolomics analysis revealed that the alterations in plasma metabolites, especially taurolithocholic acid, were significantly improved by TFRD treatment in AFB1-exposed chickens. In addition, these metabolites were closely associated with [Ruminococcus], ACC, and GPX1, indicating that AFB1 may cause liver injury by inducing bile acid metabolism involving the microbiota-gut-liver axis. We further found that TFRD treatment markedly suppressed oxidative stress and hepatic lipid deposition, increased plasma glutathione (GSH) concentrations, and reversed hepatic ferroptosis gene expression. Collectively, these findings indicate that ferroptosis might contribute to the hepatotoxicity of AFB1-exposed chickens through the microbiota-gut-liver axis interaction mechanisms; furthermore, TFRD was confirmed as an herbal extract that could potentially antagonize mycotoxins detrimental effects.

L-2-Oxothiazolidine-4-Carboxylate, a Cysteine Precursor, Stimulates Growth and Normalizes Tissue Glutathione Concentrations in Rats Fed a Sulfur Amino Acid-Deficient Diet

The efficiency of L-2-oxothiazolidine-4-carboxylate, a cysteine precursor, in stimulating glutathione synthesis and growth was evaluated in growing rats. Animals were fed a sulfur amino acid-deficient diet (0.25% L-methionine and no cysteine) supplemented with L-2-oxothiazolidine-4-carboxylate (0.35%) for 3 wk and compared with age-matched animals receiving the sulfur amino acid-deficient diet alone. Rats fed the sulfur amino acid-deficient diet had lower glutathione concentrations in bronchoalveolar lining fluid, lung, lymphocytes, and liver than rats fed a sulfur amino acid-deficient diet supplemented with L-2-oxothiazolidine-4-carboxylate. Rats fed the supplemented diet had normal tissue and bronchoalveolar lining fluid glutathione levels. Central venous plasma glutathione concentrations, mostly reflecting liver excretion, were less affected by L-2-oxothiazolidine-4-carboxylate supplementation. Rats fed L-2-oxothiazolidine-4-carboxylate supplementation had normal weight gain compared with a much lower weight gain in animals fed the sulfur amino acid-deficient diet alone. Thus, L-2-oxothiazolidine-4-carboxylate increased tissue glutathione concentrations and stimulated growth in rats. The lung glutathione status of the rats was reflected by glutathione concentrations in lymphocytes and the bronchoalveolar lining fluid, but not by the central venous plasma glutathione concentrations.

Differential hypoxia tolerance of eastern oysters from the northern Gulf of Mexico at elevated temperature

Increasing prevalence of hypoxia in shallow waters of U.S. Gulf of Mexico (GoM) estuaries can pose a serious threat to eastern oysters (Crassostrea virginica). Their tolerance to hypoxia, however, is not well characterized, especially at elevated temperatures (>30 °C) typical of GoM estuaries in summer. Moreover, it is unknown whether differences in hypoxia tolerance exist between GoM oyster populations growing in estuaries differing in local environmental conditions. Wild oyster broodstocks were collected from four estuarine sites in Texas (Packery Channel, PC and Aransas Bay, AB) and Louisiana (Calcasieu Lake, CL and Vermilion Bay, VB) and their adult progenies (F1) were tested (Study 1) under continuous hypoxia (<2.0 mg O2 L−1) at 32 °C. Significant differences in hypoxia tolerance were found between F1 populations with calculated median lethal time (LT50) ranging from 3.9 to 12.5 days. PC and CL oysters were the most and least tolerant populations, respectively. The study was repeated twice more (Studies 2 and 3) using PC and CL oysters, and their responses at the organismic, cellular, and biochemical levels were investigated. Valve movement was monitored, and oysters were sampled to measure hemocyte density, plasma protein, calcium and glutathione concentrations, and digestive gland alanine and succinate concentrations after either 3–5 days (Study 2) or 1–3 days (Study 3) of hypoxia exposure. From the onset of hypoxia until their death, oysters stayed opened 13–32% of the time compared to 53–64% under normoxia, but no differences between populations were detected under hypoxia. PC oyster but not CL oyster plasma glutathione concentrations increased significantly in both studies. Under longer (3–5 days) hypoxia exposure, plasma calcium and glutathione concentrations of PC oysters were significantly higher than CL oysters. These results suggest PC oysters were better able to protect tissues against acidosis and oxidative damage during hypoxia and high temperature stress than CL oysters. Overall, our results indicate that oyster populations originating from the GoM vary in their response to hypoxia and high temperature stress and possess differential tolerance.

Effects of dietary substitution of peanut meal for soybean meal on egg production, egg quality, oxidative status, and yolk fatty acid profile in laying ducks

There is an urgent need to evaluate and introduce alternatives for the unsustainable and traditional feed stuffs in poultry. This study evaluated the effects of graded replacement of soybean meal (SBM) by peanut meal (PNM) on egg production, egg quality, oxidative status, and yolk fatty acid profile in laying ducks. In total, 360 Longyan ducks aged 21 weeks were allocated to five treatments, each containing six replicates of 12 birds. Birds were fed the diets containing PNM replacing 0 (control), 25, 50, 75 or 100% of SBM for 16 weeks. With the increase of PNM level, egg production was improved (quadratic, P < 0.05), egg weight and feed consumption were decreased, feed conversion ratio and egg mass were impaired at 100% PNM, and yolk colour was enhanced (quadratic, P < 0.05). Plasma malondialdehyde concentration was increased at 100% PNM, while plasma glutathione concentration was decreased (quadratic, P < 0.01) as PNM substitution increased. Total cholesterol content in yolk decreased (P < 0.01) in response to increased PNM substitution. The contents of saturated fatty acids C20:0 and C22:0 in yolk increased (linear or quadratic, P < 0.05) with increased PNM substitution, but the contents of saturated fatty acid C18:0, monounsaturated fatty acid C22:1, and polyunsaturated fatty acids C18:3n-3 and C22:6n-3 in yolk were decreased (linear, P < 0.05) as PNM replacement increased. The contents in yolk of polyunsaturated fatty acid C18:2n-6, C20:2n-6, C20:3n-6, C20:4n-6, and total amount of polyunsaturated fatty acids increased with the highest contents obtained at 75% PNM substitution. The ratio between n-6 and n-3 increased (linear, P < 0.05) as PNM substitution increased. The transcript abundance in liver of peroxisome proliferators-activated receptors γ and fatty acid synthase showed quadratic (P < 0.05) responses with PNM replacement, with the highest expression of both genes being obtained with 75% substitution with PNM. Replacement of dietary SBM with 100% PNM decreased egg production and antioxidant capacity and increased the ratio of omega fatty acid in yolk between n-6 and n-3 in laying ducks. The obtained results indicate that PNM can be used to replace up to 75% of SBM in the diet of laying ducks without negative effects on the egg-laying production or egg quality. The regression model indicated that the maximal egg mass was obtained at no more than 67.6% replacement of SBM with PNM in the diet of laying ducks.

In Vitro Reactivity of the Glucose Degradation Product 3,4-Dideoxyglucosone-3-ene (3,4-DGE) towards Abundant Components of the Human Blood Circulatory System.

3,4-Dideoxyglucosone-3-ene (3,4-DGE) is a glucose degradation product present in processed foods and medicinal products. Additionally, its constant formation from 3-deoxyglucosone in plasma has been suggested. Due to its α,β-unsaturated dicarbonyl moiety, 3,4-DGE is highly reactive and has shown harmful effects in vitro. Here, we investigated the impact of major components of the human blood circulatory system on 3,4-DGE in vitro. Under physiological conditions, plasma concentrations of human serum albumin (HSA) reacted efficiently with 3,4-DGE, resulting in only 8.5% of the initial 3,4-DGE concentration after seven hours (vs. 83.4% without HSA, p < 0.001). Thereby, accessible thiol groups were reduced from 0.121 to 0.064 mol/mol HSA, whereas ketoprofen binding and esterase-like activity of HSA were not affected. Plasma concentrations of glutathione (GSH) reacted immediately and completely with 3,4-DGE, leading to two stereoisomeric adducts. Plasma concentrations of immunoglobulin G (IgG) bound to 3,4-DGE to a lower extent, resulting in 62.6% 3,4-DGE after seven hours (vs. 82.2% in the control, p < 0.01). Immobilized human collagen type IV did not alter 3,4-DGE concentrations. The results indicated that particularly HSA, GSH, and IgG readily scavenge 3,4-DGE after its appearance in the blood stream, which may be associated with a reduced antioxidative and cytoprotective activity for the living cells and, thus, the human organism by blocking free thiol groups.

Lower plasma glutathione, choline, and betaine concentrations are associated with fatty liver in postmenopausal women

Postmenopausal women are at high risk of hepatic steatosis, which may be associated one-carbon metabolism (OCM) abnormalities. We hypothesized that lower folate, choline, betaine, and glutathione (GSH) concentrations but higher total homocysteine and trimethylamine N-oxide concentrations are associated with fatty liver (FL) in postmenopausal women. We aimed to identify relationships between OCM and nonalcoholic fatty liver disease biomarkers in postmenopausal women. A total of 131 postmenopausal women participated in this study and were stratified by the incidence of FL based on the hepatic steatosis index (HSI). Food intake was evaluated using dietary records. Aspartate aminotransferase and alanine aminotransferase concentrations in serum were measured using the colorimetric method. Total homocysteine and GSH concentrations in plasma were measured using high-performance liquid chromatography. Folate and phosphatidylcholine (PC) concentrations were determined in red blood cells using an enzyme-linked immunosorbent assay. Other OCM biomarkers concentrations were measured using the isotope dilution analysis. Women with FL (HSI > 36) had lower GSH, choline, and betaine concentrations than women without FL (HSI < 36). Higher HSI level was negatively correlated with betaine and PC and positively correlated with plasma choline/betaine ratio. Lower GSH and higher carnitine concentrations in the blood are associated with an increased risk of FL. MTHFR (rs180130) T-allele carriers had lower levels of GSH than the CC homozygotes. Postmenopausal women with FL have lower GSH, choline, and betaine concentrations, which may play a role in fat accumulation in the liver. It seems important to consider the dietary intakes of these nutrients in postmenopausal women.

Alleviation of Dyslipidemia via a Traditional Balanced Korean Diet Represented by a Low Glycemic and Low Cholesterol Diet in Obese Women in a Randomized Controlled Trial.

A traditional balanced Korean diet (K-diet) may improve energy, glucose, and lipid metabolism. To evaluate this, we conducted a randomized crossover clinical trial, involving participants aged 30–40 years, who were randomly assigned to two groups—a K-diet or westernized Korean control diet daily, with an estimated energy requirement (EER) of 1900 kcal. After a 4-week washout period, they switched the diet and followed it for 4 weeks. The carbohydrate, protein, and fat ratios based on energy intake were close to the target values for the K-diet (65:15:20) and control diet (60:15:25). The glycemic index of the control diet and the K-diet was 50.3 ± 3.6 and 68.1 ± 2.9, respectively, and daily cholesterol contents in the control diet and K-diet were 280 and 150 mg, respectively. Anthropometric and biochemical parameters involved in energy, glucose, and lipid metabolism were measured while plasma metabolites were determined using UPLC-QTOF-MS before and after the 4-week intervention. After the four-week intervention, both diets improved anthropometric and biochemical variables, but the K-diet significantly reduced them compared to the control diet. Serum total cholesterol, non-high-density lipoprotein cholesterol, and triglyceride concentrations were significantly lower in the K-diet group than in the control diet group. The waist circumference (p = 0.108) and insulin resistance index (QUICKI, p = 0.089) tended to be lower in the K-diet group than in the control diet group. Plasma metabolites indicated that participants in the K-diet group tended to reduce insulin resistance compared to those in the control diet group. Amino acids, especially branched-chain amino acids, tyrosine, tryptophan, and glutamate, and L-homocysteine concentrations were considerably lower in the K-diet group than in the control diet group (p < 0.05). Plasma glutathione concentrations, an index of antioxidant status, and 3-hydroxybutyric acid concentrations, were higher in the K-diet group than in the control diet group. In conclusion, a K-diet with adequate calories to meet EER alleviated dyslipidemia by decreasing insulin resistance-related amino acids and increasing ketones in the circulation of obese women.

Glutathione Metabolism Contributes to the Induction of Trained Immunity.

The innate immune system displays heterologous memory characteristics, which are characterized by stronger responses to a secondary challenge. This phenomenon termed trained immunity relies on epigenetic and metabolic rewiring of innate immune cells. As reactive oxygen species (ROS) production has been associated with the trained immunity phenotype, we hypothesized that the increased ROS levels and the main intracellular redox molecule glutathione play a role in the induction of trained immunity. Here we show that pharmacological inhibition of ROS in an in vitro model of trained immunity did not influence cell responsiveness; the modulation of glutathione levels reduced pro-inflammatory cytokine production in human monocytes. Single nucleotide polymorphisms (SNPs) in genes involved in glutathione metabolism were found to be associated with changes in pro-inflammatory cytokine production capacity upon trained immunity. Also, plasma glutathione concentrations were positively associated with ex vivo IL-1β production, a biomarker of trained immunity, produced by monocytes of BCG-vaccinated individuals. In conclusion, glutathione metabolism is involved in the induction of trained immunity, and future studies are warranted to explore its functional consequences in human diseases.

Altered oxidative stress markers in relation to T cells, NK cells & killer immunoglobulin receptors that are associated with disease activity in SLE patients.

Systemic Lupus Erythematosus is an autoimmune disease with symptoms pervasive to all organ systems. It affects more females as compared to males (in the ratio 9:1). Oxidative stress plays a major role in the pathogenesis of SLE and other autoimmune diseases. In order to understand the relationship between cell specific oxidative stress and the severity of SLE, this research study involving the estimation of intracellular ROS accumulation in T and NK cell was conducted on SLE patients of North Indian Population. At the same time, to estimate anti-oxidant defense, Keap1 and Nrf2 levels were estimated in these cell types. The relationship between the expression of Killer immunoglobulin receptors i.e., KIR2DL4 & KIR3DL1 and oxidative stress was also evaluated as these receptors are imperative for the function and self-tolerance of NK cells.Oxidative stress was raised along with Keap1 and Nrf2 in T and NK cell subsets in SLE patients. The expression of KIR2DL4 was raised and that of KIR3DL1 was reduced in the NK cells of patients. The intensity of change in expression and its significance varied among the subsets. Nrf2 expression was raised in these species against oxidative stress as the antioxidant defense mechanism pertaining to Keap1-Nrf2 pathway, but the adequacy of response needs to be understood in further studies. The expression of KIR2DL4 and KIR3DL1 varied among the patient and healthy controls and the expression of the latter was found to have a significant positive relationship with plasma Glutathione(reduced) concentration.

Biomarkers of oxidative stress as an assessment of the redox status of the liver in dogs.

BackgroundOxidative stress is associated with a diverse group of liver disorders across species.ObjectivesDetermine whether glutathione (GSH) concentration in plasma and red blood cells correlates with liver GSH concentration in dogs and evaluate whether other markers of systemic oxidative stress, plasma vitamin E and urine 8‐isoprostanes/creatinine (F2‐IsoPs/Cr) concentrations, correlate with liver GSH.AnimalsThirty‐four client‐owned dogs undergoing clinically indicated liver biopsy and 15 healthy control dogs.MethodsProspective, observational cross‐sectional study. Urine and blood were collected before liver biopsy. Plasma, erythrocyte, and liver GSH were measured using high performance liquid chromatography (HPLC); vitamin E was measured by HPLC, and F2‐IsoPs/Cr was measured by gas chromatography/mass spectrometry.ResultsAll dogs were treated at the discretion of the attending clinician (24/34 received antioxidants; 4/34 fed therapeutic liver diet), which included dogs with primary or secondary liver disease (inflammatory (n = 21), metabolic (n = 9), vascular (n = 2), and neoplastic (n = 2)). Median GSH concentrations in plasma, erythrocyte, and liver were 0.18 mg/dL (range 0.14 to 0.56 mg/dL), 56.7 mg/dL (18.3 to 79.2 mg/dL), and 181 mg/dL (39.9 to 527 mg/dL), respectively. No significant correlations were found between liver GSH and erythrocyte GSH, plasma GSH, vitamin E, or F2‐IsoPs/Cr. Dogs undergoing clinically indicated liver biopsy had significantly higher urine F2‐IsoPs/Cr than did healthy controls (5.89 vs 2.98 ng/mg; P < .0001).Conclusions and Clinical ImportanceErythrocyte and plasma GSH are not indicative of liver GSH concentration in dogs. In addition, dogs undergoing clinically indicated liver biopsy have evidence of increased systemic oxidative stress compared to healthy controls.

Azithromycin in Combination with Ceftriaxone Reduces Systemic Inflammation and Provides Survival Benefit in a Murine Model of Polymicrobial Sepsis.

Sepsis is a life-threatening systemic inflammatory condition triggered as a result of an excessive host immune response to infection. In the past, immunomodulators have demonstrated a protective effect in sepsis. Azithromycin (a macrolide antibiotic) has immunomodulatory activity and was therefore evaluated in combination with ceftriaxone in a clinically relevant murine model of sepsis induced by cecal ligation and puncture (CLP). First, mice underwent CLP and 3 h later were administered the vehicle or a subprotective dose of ceftriaxone (100 mg/kg of body weight subcutaneously) alone or in combination with an immunomodulatory dose of azithromycin (100 mg/kg intraperitoneally). Survival was monitored for 5 days. In order to assess the immunomodulatory activity, parameters such as plasma and lung cytokine (interleukin-6 [IL-6], IL-1β, tumor necrosis factor alpha) concentrations, the plasma glutathione (GSH) concentration, plasma and lung myeloperoxidase (MPO) concentrations, body temperature, blood glucose concentration, and total white blood cell count, along with the bacterial load in blood, peritoneal lavage fluid, and lung homogenate, were measured 18 h after CLP challenge. Azithromycin in the presence of ceftriaxone significantly improved the survival of CLP-challenged mice. Further, the combination attenuated the elevated levels of inflammatory cytokines and MPO in plasma and lung tissue and increased the body temperature and blood glucose and GSH concentrations, which were otherwise markedly decreased in CLP-challenged mice. Ceftriaxone produced a significant reduction in the bacterial load, while coadministration of azithromycin did not produce a further reduction. Therefore, the survival benefit offered by azithromycin was due to immunomodulation and not its antibacterial action. The findings of this study indicate that azithromycin, in conjunction with appropriate antibacterial agents, could provide clinical benefits in sepsis.

An inverse relationship between plasma glutathione concentration and fasting glycemia in patients with coronary artery disease and concomitant type 2 diabetes: A pilot study.

There have been occasional reports indicating that plasma concentrations of reduced glutathione (GSH) may be associated in some way with blood glucose. This relationship, however, has not hitherto been explored in the blood plasma of patients with coronary artery disease (CAD). The aim of this study was to evaluate potential associations of fasting glycemia and peripheral blood plasma GSH concentrations in CAD-free and CAD-affected subjects. In blood samples obtained from patients with CAD, defined by coronary angiography and/or echocardiography, and from an age-matched control group of patients with a confirmation of no coronary artery occlusion and with no history of cardiovascular events, plasma concentrations of glucose and reduced glutathione were analyzed by routine laboratory diagnostic methods and high performance liquid chromatography (HPLC), respectively. The results showed that in the CAD patients, but not in the non-CAD controls, fasting glycemia is negatively associated with plasma levels of GSH (r = -0.328; p = 0.011). Moreover, in the CAD-affected subjects (but not in the controls) the presence of type 2 diabetes mellitus significantly discriminated plasma levels of GSH (rP = -0.125; p = 0.350, between GSH and glucose adjusted for the occurrence of diabetes). The study suggests that GSH may be an important factor contributing to glucose metabolism in CAD patients. Hence, it may be considered a significant therapeutic target in strategies aimed at improving glycemic control in CAD-affected subjects.

The effect of DL-, L-isomers and DL-hydroxy analog administered at 2 levels as dietary sources of methionine on the metabolic and antioxidant parameters and growth performance of turkeys

A hypothesis was verified that dietary methionine (Met) improves the growth and antioxidant status of turkeys, and that its effects depend on dietary inclusion levels and sources. A total of 816 female Hybrid Converter turkeys was fed wheat-soybean meal-based diets supplemented with 3 sources of Met: DL-, L-isomers and DL-hydroxy analog (DLM, LM, and MHA, respectively). In 4 4-week periods (from one to 16 wk of age), dietary Met content corresponded to NRC (1994) recommendations or was increased by approximately 50% (in one to 8 wk by 44 to 46% and in 9 to 16 wk by 55 to 56% vs. the NRC guidelines) to match the recommendations of some breeding companies. Increased Met content resulted in higher final body weights of turkeys (P = 0.002), an improved feed conversion ratio (P = 0.049), increased total glutathione concentration and ferric reducing ability of plasma (FRAP) values, and decreased malondialdehyde (MDA) concentration (all P < 0.001) in the blood plasma of turkeys. In comparison with DLM, LM and MHA contributed to an increase in plasma glutathione concentration (P = 0.001), a decrease in plasma triacylglycerol (P = 0.003) and uric acid (P = 0.001) concentrations, and a decrease in liver MDA (P = 0.001) levels. A decrease in plasma MDA (vs. DLM) and lipid peroxides (LOOH) (vs. DLM and LM) concentrations as well as a decrease in plasma superoxide dismutase (SOD) activity (vs. DLM and LM) also were noted in the MHA treatment (P = 0.016, P = 0.001 and P = 0.011, respectively). In conclusion, the results of the study indicate that the antioxidant status of turkeys could be affected by dietary Met levels and sources. The dietary Met content increased by 50% relative to NRC recommendations, improved the growth performance of turkeys, and strengthened their antioxidant defense system. In comparison with DLM, LM and MHA could be considered positive nutritional factors as manifested by a beneficial decrease in plasma and hepatic MDA concentrations as well as an increase in plasma glutathione levels, and the effect of MHA was more pronounced.

Ageing is not associated with an altered immune response during Trypanosoma cruzi infection: Ageing and Trypanosoma cruzi infection

The aims of this work were to evaluate the influence of ageing on the magnitude of the immune response in male Wistar rats infected with the Y strain of Trypanosoma cruzi (T. cruzi). Infected young animals displayed enhanced CD4+ T cells as compared to uninfected counterparts. Ageing also triggered a significant reduction in CD8+ T cells compared to young and uninfected groups. The percentage of spleen NKT cells was reduced for all groups, regardless of the infection status. Significant decreased B-cells was noted in aged controls and infected animals as compared to young counterparts. A significant decrease in MHC class II (RT1B) expression in all aged animals was observed, whether infected or not. The highest and significant levels of Thiobarbituric Acid Reactive Substances (TBARS) were noted in the aged and infected animals as compared to young-infected ones (16day). Consequently superoxide dismutase (SOD) activity was reduced for both control and infected aged animals. Significant elevation of 8-isoprostane levels was found in aged control and infected animals. Plasma glutathione (GSH) concentration was reduced in aged control animals, as well as, in the young infected animals. NO production was increased in both infected and uninfected aged animals compared to young infected and uninfected animals. Corticosterone levels were elevated in aged animals, whether infected or not. Thus, our results are inedited since the immune response is not worsened by the simple fact of animals being older. Ageing by itself triggered a damaged immune response as well as enhanced reactive oxygen species, when compared to young counterparts, but it did not contribute to impair the immune response of T. cruzi infected and aged rats.

Ascorbylperoxide Contaminating Parenteral Nutrition Is Associated With Bronchopulmonary Dysplasia or Death in Extremely Preterm Infants.

Ascorbylperoxide (AscOOH) is a hydrogen peroxide-dependent by-product of ascorbic acid that contaminates parenteral nutrition. In a guinea pig model, it caused oxidized redox potential, increased apoptosis, and decreased alveolarization. AscOOH detoxification is carried out by glutathione peroxidase (GPX). We hypothesize that extremely preterm infants have limited capacity for AscOOH detoxification. Our objective was to determine if there is an association between an early level of urinary AscOOH and later development of bronchopulmonary dysplasia (BPD) or death. This prospective cohort study included 51 infants at <29 weeks of gestation. Baseline clinical characteristics and clinical outcomes data were collected. Urine samples were collected on days 3, 5, and 7 of life for urinary AscOOH. Blood samples on day 7 were collected for total plasma glutathione, GPX, and glutathione reductase. χ2, Student's t test, Spearman correlation ( r), linear regression (adjusted r2), and repeated-measure analysis of variance were used as appropriate. P < .05 was considered significant. Urinary AscOOH increased over time ( P = .001) and was higher in infants who later developed BPD or died ( P = .037). Compared with adults and full-term infants, total plasma glutathione concentration was low (median, 1.02 µmol/L; 25th-75th percentiles, 0.49-1.76 µmol/L), whereas GPX and glutathione reductase activities were sufficient (3.98 ± 1.25 and 0.36 ± 0.01 nmol/min/mg of protein, respectively). Extremely preterm infants have low glutathione levels, which limit their capacity to detoxify AscOOH. Higher first-week urinary AscOOH levels are associated with an increased incidence of BPD or death.