Plasma Protein Carbonyl Research Articles

Impact of BMI and Cardiorespiratory Fitness on Oxidative Stress in Plasma and Circulating Exosomes Following Acute Exercise.

The impact of cardiorespiratory fitness (VO2max) and obesity on indices of oxidative stress in plasma and circulating exosome-like extracellular vesicles (ELVs) were examined following acute exercise. Indices of oxidative stress in plasma and isolated plasma ELVs were examined in aerobically trained (NW-Tr; n = 15) and untrained (NW-UTr; n = 18) normal-weight individuals and aerobically untrained individuals with obesity (Ob-Utr; n = 10) prior to and immediately following acute maximal treadmill running. Following exercise, ELV flotillin-1 expression (p = 0.008) and plasma total antioxidant capacity (TAC; p = 0.010) increased more in NW-UTr compared to NW-Tr and Ob-UTr participants, whereas plasma protein carbonyls (PC) decreased more in Ob-UTr compared to NW-Tr and NW-UTr groups. ELV glutathione (GSH) concentrations decreased more in NW-Tr compared to NW-UTr and Ob-UTr participants (p = 0.009), whereas lipid peroxidase (LPO) concentrations increased more in Ob-UTr compared to NW-Tr and NW-UTr participants (p = 0.003). Body mass index (BMI) was associated negatively with plasma TAC and PC (p < 0.05) and positively with ELV LPO concentration responses (p = 0.009). Finally, plasma-to-total (plasma + ELV) GSH ratios decreased in Ob-UTr compared to NW-Tr and NW-UTr participants (p = 0.006), PC ratios increased in NW-Tr and NW-UTr compared to Ob-UTr subjects (p = 0.008), and reactive oxygen/nitrogen species ratios increased in NW-UTr and decreased in Ob-UTr participants (p < 0.001). BMI, independently of VO2max, differentially regulates indices of oxidative stress within plasma and circulating ELVs prior to and immediately following acute maximal treadmill exercise.

Supplementation of vitamin E as an addition to a commercial renal diet does not prolong survival of cats with chronic kidney disease

BackgroundThe aim of this double-blind, placebo-controlled study was to investigate the effect of vitamin E supplementation as an addition to a commercial renal diet on survival time of cats with different stages of chronic kidney disease (CKD). In addition, we were interested whether vitamin E supplementation affects selected oxidative stress and clinical parameters. Thirty-four cats with CKD and 38 healthy cats were included in the study. Cats with CKD were classified according to the IRIS Guidelines; seven in IRIS stage 1, 15 in IRIS stage 2, five in IRIS stage 3 and seven in IRIS stage 4. Cats with CKD were treated according to IRIS Guidelines. Cats with CKD were randomly assigned to receive vitamin E (100 IU/cat/day) or placebo (mineral oil) for 24 weeks in addition to standard therapy. Plasma malondialdehyde (MDA) and protein carbonyl (PC) concentrations, DNA damage of peripheral lymphocytes and plasma vitamin E concentrations were measured at baseline and four, eight, 16 and 24 weeks thereafter. Routine laboratory analyses and assessment of clinical signs were performed at each visit.ResultsVitamin E supplementation had no effect on the survival time and did not reduce the severity of clinical signs. Before vitamin E supplementation, no significant differences in vitamin E, MDA and PC concentrations were found between healthy and CKD cats. However, plasma MDA concentration was statistically significantly higher (p = 0.043) in cats with early CKD (IRIS stages 1 and 2) than in cats with advanced CKD (IRIS stages 3 and 4). Additionally, DNA damage was statistically significantly higher in healthy cats (p ≤ 0.001) than in CKD cats. Plasma vitamin E concentrations increased statistically significantly in the vitamin E group compared to the placebo group four (p = 0.013) and eight (p = 0.017) weeks after the start of vitamin E supplementation. During the study and after 24 weeks of vitamin E supplementation, plasma MDA and PC concentrations and DNA damage remained similar to pre-supplementation levels in both the placebo and vitamin E groups.ConclusionsVitamin E supplementation as an addition to standard therapy does not prolong survival in feline CKD.

Elevated plasma protein carbonylation increases the risk of ischemic cerebrovascular events in patients with atrial fibrillation: association with a prothrombotic state.

Plasma protein carbonylation that reflects oxidative stress has been demonstrated to be associated with the prothrombotic fibrin clot phenotype. However, the role of protein carbonyls (PC) in predicting ischemic stroke in atrial fibrillation (AF) is largely unknown. This study aimed to investigate whether PC increase the risk of stroke in anticoagulated AF patients during follow-up. In 243 AF patients on anticoagulation (median age 69years; median CHA2DS2-VASc of 4), we measured plasma PC using the assay by Becatti, along with plasma clot permeability (Ks), clot lysis time (CLT), thrombin generation, and fibrinolytic proteins, including plasminogen activator inhibitor type 1 (PAI-1) and thrombin activatable fibrinolysis inhibitor (TAFI). Ischemic stroke, major bleeding, and mortality were recorded during a median follow-up of 53months. Plasma PC levels (median, 3.16 [2.54-3.99] nM/mg protein) at baseline showed positive associations with age (P < 0.001), CHA2DS2-VASc (P = 0.003), and N-terminal B-type natriuretic peptide (P = 0.001), but not with type of AF or comorbidities except for heart failure (P = 0.007). PC levels were correlated with CLT (r = 0.342, P < 0.001), endogenous thrombin potential (r = 0.217, P = 0.001) and weakly with Ks (r = -0.145, P = 0.024), but not with fibrinogen, PAI-1, or TAFI levels. Stroke was recorded in 20 patients (1.9%/year), who had at baseline 36% higher PC levels (P < 0.001). Elevated PC (P = 0.003) at baseline were independently associated with stroke risk. Our findings suggest that in patients with AF enhanced protein carbonylation is associated with increased "residual" risk of stroke despite anticoagulation, which is at least in part due to unfavorably altered fibrin clot phenotype.

Anti-atherogenic role of green tea (Camellia sinensis) in South Indian smokers

Ethnopharmacological relevanceGreen tea (Camellia sinensis) is a popular beverage consumed all over the world due to its health benefits. Many of these beneficial effects of green tea are attributed to polyphenols, particularly catechins. Aim of the studyThe present study focuses on underlying anti-platelet aggregation, anti-thrombotic, and anti-lipidemic molecular mechanisms of green tea in South Indian smokers. Materials and methods: We selected 120 South Indian male volunteers for this study to collect the blood and categorised them into four groups; control group individuals (Controls), smokers, healthy control individuals consuming green tea, and smokers consuming green tea. Smokers group subjects have been smoking an average 16–18 cigarettes per day for the last 7 years or more. The subjects (green tea consumed groups) consumed 100 mL of green tea each time, thrice a day for a one-year period. ResultsLC-MS analysis revealed the presence of multiple phytocompounds along with catechins in green tea extract. Increased plasma lipid peroxidation (LPO), protein carbonyls, cholesterol, triglycerides, and LDL-cholesterol with decreased HDL-cholesterol levels were observed in smokers compared to the control group and the consumption of green tea showed beneficial effect. Furthermore, docking studies revealed that natural compounds of green tea had high binding capacity with 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA) when compared to their positive controls, whereas (−) epigallocatechin-3-gallate (EGCG) and (−) epicatechin-gallate (ECG) had high binding capacity with sterol regulatory element-binding transcription factor 1 (SREBP1c). Further, our ex vivo studies showed that green tea extract (GTE) significantly inhibited platelet aggregation and increased thrombolytic activity in a dose dependent manner. ConclusionIn conclusion, in smokers, catechins synergistically lowered oxidative stress, platelet aggregation and modified the aberrant lipid profile. Furthermore, molecular docking studies supported green tea catechins' antihyperlipidemic efficacy through strong inhibitory activity on HMG-CoA reductase and SREBP1c. The mitigating effects of green tea on cardiovascular disease risk factors in smokers that have been reported can be attributed majorly to catechins or to their synergistic effects.

Longitudinal Assessment of Oxidative Stress Markers in Women with Preeclampsia.

Preeclampsia (PE) is a pregnancy-specific disorder and a major contributor to maternal and fetal morbidity and mortality. Role of oxidative stress in early pregnancy with the pathophysiology of the disorder is unclear. The current study aims to analyse maternal levels of oxidative stress markers (MDA and protein carbonyl) longitudinally across gestation and placental levels of oxidative stress markers (MDA, protein carbonyl and 8-oxo-2'-deoxyguanosine) in women with PE and compare them with non-PE women. 324 pregnant women (216 non-PE and 108 PE women) were longitudinally followed during pregnancy. Women with preeclampsia were stratified as early onset preeclampsia (EOP) and late onset preeclampsia (LOP) Maternal blood at four time points across gestation (11-14weeks, 18-22weeks, 26-28weeks, and at delivery) and placenta were collected. Maternal and placental levels of oxidative stress markers were assessed using commercially available kits. Maternal plasma MDA and protein carbonyl levels were comparable between the PE and non-PE group at all timepoints across gestation. Maternal plasma MDA were significantly higher levels at 26-28weeks in EOP women when compared to non-PE women (p < 0.05). Placental 8-oxo-dG levels were lower in the EOP group as compared to non-PE (p < 0.05). Elevated plasma MDA levels were positively associated with birth length at 18-22weeks and 26-28weeks in the PE group (p < 0.05 for both). Maternal plasma MDA levels were positively associated with systolic blood pressure at 18-22weeks. Oxidative stress in early pregnancy is not associated with risk of PE.

Elevated Plasma Protein Carbonyl Concentration Is Associated with More Abnormal White Matter in People with HIV.

Structural brain abnormalities, including those in white matter (WM), remain common in people with HIV (PWH). Their pathogenesis is uncertain and may reflect multiple etiologies. Oxidative stress is associated with inflammation, HIV, and its comorbidities. The post-translational carbonylation of proteins results from oxidative stress, and circulating protein carbonyls may reflect this. In this cross-sectional analysis, we evaluated the associations between protein carbonyls and a panel of soluble biomarkers of neuronal injury and inflammation in plasma (N = 45) and cerebrospinal fluid (CSF, n = 32) with structural brain MRI. The volume of abnormal WM was normalized for the total WM volume (nAWM). In this multisite project, all regression models were adjusted for the scanner. The candidate covariates included demographics, HIV disease characteristics, and comorbidities. Participants were PWH on virally suppressive antiretroviral therapy (ART) and were mostly white (64.4%) men (88.9%), with a mean age of 56.8 years. In unadjusted analyses, more nAWM was associated with higher plasma protein carbonyls (p = 0.002) and higher CCL2 (p = 0.045). In the adjusted regression models for nAWM, the association with plasma protein carbonyls remained significant (FDR p = 0.018). Protein carbonyls in plasma may be a valuable biomarker of oxidative stress and its associated adverse health effects, including within the central nervous system. If confirmed, these findings would support the hypothesis that reducing oxidative stress could treat or prevent WM injury in PWH.

Protein Carbonylation Contributes to Prothrombotic Fibrin Clot Phenotype in Acute Ischemic Stroke: Clinical Associations.

Acute ischemic stroke (AIS) is associated with enhanced oxidative stress and unfavorably altered fibrin clot properties. We investigated determinants of plasma protein carbonylation (PC) in AIS, its impact on the prothrombotic state, and prognostic value during follow-up. We included 98 consecutive AIS patients aged 74±12 years (male:female ratio, 50:48 [51%:49%]) at the Neurology Center in Warsaw, Poland, between January and December 2014. As many as 74 (75.5%) patients underwent thrombolysis, and 24 were unsuitable for thrombolysis. We determined plasma PC, along with thrombin generation, fibrin clot permeability, and clot lysis time on admission, at 24 hours, and 3 months. Stroke severity was assessed using the National Institutes of Health Stroke Scale and stroke outcome with the modified Rankin Scale. Hemorrhagic transformation was assessed on the computed tomography scan within 48 hours from the symptom onset, while stroke-related mortality was evaluated at 3 months. On admission, PC levels (median, 4.61 [3.81-5.70] nM/mg protein) were associated with the time since symptom onset (r=0.41; P<0.0001) and with the National Institutes of Health Stroke Scale score (P=0.36; P=0.0003). Higher PC levels on admission correlated with denser fibrin clot formation and prolonged clot lysis time but not with thrombin generation. In thrombolysed patients, lower PC levels were observed after 24 hours (-34%) and at 3 months (-23%; both P<0.001). PC levels at baseline and after 24 hours predicted the modified Rankin Scale score >2 at 3 months (OR, 1.90 [95% CI, 1.21-3.00]; OR, 2.19 [95% CI, 1.39-3.44], respectively). Higher PC at baseline predicted hemorrhagic transformation of stroke (OR, 1.95 [95% CI, 1.02-3.74]) and stroke-related mortality (OR, 2.02 [95% CI, 1.08-3.79]), while higher PC at 24 hours predicted solely stroke-related mortality (OR, 2.11 [95% CI, 1.28-3.46]). Elevated plasma PC levels in patients with AIS, related to prothrombotic fibrin clot properties, are associated with stroke severity. Thrombolysis reduces the extent of PC. The current study suggests a prognostic value of PC in AIS.

PB0016 Plasma Protein Carbonylation is Associated with Unfavorably Altered Fibrin Clot Properties in Patients with Atrial Fibrillation: A Novel Risk Factor of Ischemic Cerebrovascular Events

PB0016 Plasma Protein Carbonylation is Associated with Unfavorably Altered Fibrin Clot Properties in Patients with Atrial Fibrillation: A Novel Risk Factor of Ischemic Cerebrovascular Events

PB0036 Plasma Protein Carbonyl Levels Contribute to Prothrombotic Fibrin Clot Phenotype in Acute Ischemic Stroke Patients: Associations with Clinical Outcomes

PB0036 Plasma Protein Carbonyl Levels Contribute to Prothrombotic Fibrin Clot Phenotype in Acute Ischemic Stroke Patients: Associations with Clinical Outcomes

Arsenic exposure incurs hyperglycemia mediated by oxidative damage in urban adult population: A prospective cohort study with three repeated measures

The associations and potential mechanisms of low to moderate arsenic exposure with fasting plasma glucose (FPG) and type 2 diabetes mellitus (T2DM) are still unclear. To assess the effects of short-term and long-term arsenic exposure on hyperglycemia and the mediating effect of oxidative damage on such association, three repeated-measures studies with 9938 observations were conducted in the Wuhan-Zhuhai cohort. The levels of urinary total arsenic, FPG, urinary 8-iso-prostaglandin F2alpha (8-iso-PGF2α), urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), and plasma protein carbonyls (PCO) were measured. Generalized linear mixed models were used to evaluate the exposure-response relationships of urinary total arsenic with FPG and the prevalent risks of impaired fasting glucose (IFG), T2DM, and abnormal glucose regulation (AGR). Cox regression models were applied to assess the associations of arsenic exposure with incident risks of IFG, T2DM, and AGR. Mediation analyses were performed to assess the mediating effects of 8-iso-PGF2α, 8-OHdG, and PCO. In cross-sectional analyses, each one-unit increase in natural log-transformed urinary total arsenic was associated with a 0.082 (95% CI: 0.047 to 0.118) mmol/L increase in FPG, as well as a 10.3% (95% CI: 1.4%–20.0%), 4.4% (95% CI: 5.3%–15.2%), and 8.7% (95% CI: 1.2%–16.6%) increase in prevalent risks of IFG, T2DM, and AGR, respectively. In longitudinal analyses, arsenic exposure was further associated with the annual increased rate of FPG with a β (95% CI) of 0.021 (95% CI: 0.010 to 0.033). The incident risks of IFG, T2DM, and AGR were increased without statistical significance when arsenic levels increased. Mediation analyses showed that 8-iso-PGF2α and PCO mediated 30.04% and 10.02% of the urinary total arsenic-associated FPG elevation, respectively. Our study indicated that arsenic exposure was associated with elevated level and progression rate of FPG among general Chinese adults, where lipid peroxidation and oxidative protein damage might be the potential mechanisms.

Carbon disulfide exposure induced lung function reduction partly through oxidative protein damage: A cross-sectional and longitudinal analysis

Carbon disulfide (CS2) exposure has been associated with lung function reduction in occupational population. However, evidence on the general population with relatively low CS2 exposure is lacking and the mechanism involved remains largely unknown. Urinary CS2 metabolite (2-mercaptothiazolidine-4-carboxylic acid, TTCA) and lung function were determined in the urban adults from the Wuhan-Zhuhai cohort at baseline in 2011–2012 and were repeated every 3 years. Cross-sectional and longitudinal associations between TTCA and lung function were estimated using linear mixed models. Inflammation and oxidative damage biomarkers in blood/urine were measured to evaluate their potential mediating roles involved. Cross-sectionally, participants in the highest quartile of TTCA level showed a 0.64% reduction in FEV1/FVC and a −308.22 mL/s reduction in PEF, compared to those in the lowest quartile. Longitudinally, participants with consistently high TTCA level had annually −90.27 mL/s decline in PEF, compared to those with consistently low TTCA level. Mediation analysis revealed that plasma protein carbonyl mediated 49.89% and 22.10% of TTCA-associated FEV1/FVC and PEF reductions, respectively. Conclusively, there was a cross-sectional and longitudinal association between CS2 exposure and lung function reduction in the general urban adults, and protein carbonylation (oxidative protein damage) partly mediated lung function reduction from CS2 exposure.

Effects of aging and type 2 diabetes on cardiac structure and function: Underlying mechanisms

We characterized long-term changes in cardiac structure and function in a high-fat diet/streptozotocin mouse model of aging and type 2 diabetes mellitus (T2D) and examined how the intersection of both conditions alters plasma metabolomics. We also evaluated the possible roles played by oxidative stress, arginase activity and pro-inflammatory cytokines. C57BL/6 male mice (13-month-old) were used. Control animals (n = 13) were fed regular chow for 10 months (aged group). T2D animals (n = 25) were provided a single injection of streptozotocin and fed a high fat diet for 10 months. In select endpoints, young animals were used for comparison. To monitor changes in left ventricular (LV) structure and function, echocardiography was used. At the terminal study (23 months), blood was collected and hearts processed for biochemical or histological analysis. Echo yielded diminished diastolic function with aging and T2D. LV fractional shortening and ejection fraction decreased with T2D by 16 months peaking at 23 months. Western blots noted increases in fibronectin and type I collagen with aging/T2D and greater levels with T2D in α-smooth muscle actin. Increases in plasma and/or myocardial protein carbonyls, arginase activity and pro-inflammatory cytokines occurred with aging and T2D. Untargeted metabolomics and cheminformatics revealed differences in the plasma metabolome of T2D vs. aged mice while select classes of lipid metabolites linked to insulin resistance, were dysregulated. We thus, document changes in LV structure and function with aging that in select endpoints, are accentuated with T2D and link them to increases in OS, arginase activity and pro-inflammatory cytokines.

Supplementation with rice bran hydrolysates reduces oxidative stress and improves lipid profiles in adult dogs.

Oxidative stress is defined as an imbalance between reactive oxygen species (ROS) production and antioxidant defense mechanisms of the body. An overproduction of ROS leads to lipid and protein oxidation, injuring the cells both in normal and pathological conditions. Rice bran protein hydrolysates (RBH) has potent antioxidant, anti-inflammatory, anti-angiotensin converting enzyme (ACE) and hypolipidemic effects. Little is known, however, about the effects of RBH in dogs. The present study evaluated the antioxidative, anti-ACE and metabolic effects of RBH in adult dogs. Eighteen adult dogs were divided into 2 groups: control (n=7) and RBH supplemented groups (n=11), received a diet with the same nutritional compositions. The RBH supplemented group was fed with RBH 500 mg/kg body weight (BW) mixed with food for 30 days. BW, blood glucose, lipid profiles, liver enzymes, electrocardiography (ECG), plasma ACE activity, oxidative stress and antioxidant biomarkers were determined on day 0 and day 30 of supplementation periods. Results showed that RBH decreased oxidative stress and increased antioxidant biomarkers by significantly reducing plasma malondialdehyde (MDA) and protein carbonyl, enhanced blood glutathione (GSH) and improved the GSH redox ratio. Moreover, decreased LDL-C and increased HDL-C levels were found after RBH supplementation whereas BW, blood glucose, liver enzymes, plasma ACE activity, plasma catalase (CAT) and superoxide dismutase (SOD) activity and cardiac function were not significantly changed. These results suggest that RBH may help to lower the risk of oxidative stress and dyslipidemia in adult dogs.

Cross-sectional and Longitudinal Associations Between Propylene Oxide Exposure and Lung Function Among Chinese Community Residents: Roles of Oxidative DNA Damage, Lipid Peroxidation, and Protein Carbonylation

Toxicologic studies have reported propylene oxide (PO) exposure may harm the respiratory system, but the association between PO exposure and lung function and potential mechanism remains unclear. What is the association between PO exposure and lung function and potential mediating mechanism? Urinary PO metabolite [N-Acetyl-S-(2-hydroxypropyl)-L-cysteine (2HPMA)] as PO internal exposure biomarker and lung function were measured for 3,692 community residents at baseline and repeated at 3-year follow up. Cross-sectional and longitudinal associations between urinary 2HPMA and lung function were assessed by linear mixed model. Urinary 8-hydroxy-deoxyguanosine, urinary 8-iso-prostaglandin-F2α, and plasma protein carbonyls as biomarkers of oxidative DNA damage, lipid peroxidation, and protein carbonylation, respectively, were measured for all participants to explore their potential roles in 2HPMA-associated lung function decline by mediation analysis. After adjustment for potential covariates, each threefold increase in urinary 2HPMA was cross sectionally associated with a 26.18mL (95%CI,-50.55 to-1.81) and a 21.83mL (95%CI,-42.71 to-0.95) decrease in FVC and FEV1, respectively, at baseline (all P< .05). After 3 years of follow up, 2HPMA was observed to be longitudinally associated with FEV1/FVC decline. No significant interaction effect of smoking or passive smoking was observed (Pinteraction > .05), and the associations between 2HPMA and lung function indexes were persistent among participants who were not smoking and those who were not passive smoking in both baseline and follow-up evaluations. We observed urinary 8-hydroxy-deoxyguanosine partially mediated the associations of 2HPMA with FVC (mediation proportion, 5.48%) and FEV1 (mediation proportion, 6.81%), and plasma protein carbonyl partially mediated the association between 2HPMA and FEV1 (mediation proportion, 3.44%). PO exposure was associated with lung function decline among community residents, and oxidative DNA damage and protein carbonylation partially mediated PO exposure-associated lung function decline. Further attention on respiratory damage caused by PO exposure is warranted.

Fluvoxamine ameliorates oxidative stress and inflammation induced by bile-duct ligation in male rats

IntroductionCholestasis is a disorder that the bile ducts were narrowed and bile acids are not released simply. Bile acids-induced liver damage is exacerbated by inflammation and oxidative stress. The goal of the current study was to investigate the protective impacts of fluvoxamine (Flu) on oxidant-antioxidant balance and inflammatory cytokines in the bile duct ligated (BDL) rats. MethodsThirty-two male rats were arbitrarily allocated in 4 groups; sham-control (SC), SC+ 150 mg/kg Flu (SCF), bile duct ligation (BDL), and BDL+ 150 mg/kg Flu (BDLF). The rats received distilled water and Flu orally for one week. Biochemical analysis, hematoxylin and eosin staining, as well as oxidant/antioxidant status were evaluated. Also, the mRNA expression of TGF-β1, IL-1, TNF-α, and α-SMA were determined. ResultsThe findings indicated serum values of ALT, total bilirubin, and ALP slightly declined in the BDL + Flu group in contrast to BDL rats. The plasma protein carbonyl and inflammatory markers were markedly increased in the BDL group in contrast with SC group (P ≤ 0.05). Treatment with Flu in BDL rats markedly reduced the values of hepatic nitric oxide metabolite and malondialdehyde, plasma protein carbonyl, as well as TNF-α mRNA level (P ≤ 0.05). Histological parameters were improved in the BDL + Flu group in comparison to BDL merely rats. ConclusionIt seems that Flu declined oxidative stress probably by inhibiting lipid peroxidation, protein oxidation, and nitric oxide formation. Also, it reduced inflammation by decreasing TNF-α mRNA expression.

Associations of bifenthrin exposure with glucose homeostasis and type 2 diabetes mellitus in a general Chinese population: Roles of protein carbonylation

The adverse health effects of pyrethroids exposure have attracted wide concern. We aimed to assess the associations of bifenthrin, a widely used pyrethroid, with glucose homeostasis and risk of type 2 diabetes mellitus (T2DM) and to explore the underlying mechanism. Serum bifenthrin, fasting plasma glucose (FPG), fasting plasma insulin (FPI), and plasma protein carbonyl (PCO) were determined among 3822 participants from the Wuhan-Zhuhai cohort. Glucose homeostasis was evaluated by FPG, FPI, homeostasis model assessment of insulin resistance (HOMA-IR), impaired fasting glucose (IFG), and abnormal glucose regulation (AGR). The associations of serum bifenthrin with glucose homeostasis and risk of T2DM were assessed by generalized linear models and logistic regression models. The role of PCO in the above associations was evaluated by mediation analyses. After adjusting for covariates, each 2-fold increase in serum bifenthrin was associated with a 0.21 mmol/L increase in FPG and a 5.19%, 10.49%, and 12.18% increase in FPI, HOMA-IR, and PCO levels, respectively. Monotonically elevated ORs of IFG and AGR (all P and P for trend <0.05), but not T2DM (P > 0.05) were detected to be associated with increased bifenthrin. Compared with the participants with low bifenthrin and low PCO, participants with high bifenthrin exposure and high PCO showed a 0.40 mmol/L, 11.07%, and 22.50% increase in FPG, FPI, and HOMA-IR, as well as a 119.97% and 48.88% increase in risks of IFG and AGR, respectively (P for trend <0.05). Moreover, PCO mediated 13.61%–24.98% of the serum bifenthrin-associated glucose dyshomeostasis. The study suggested that bifenthrin exposure was dose-dependently associated with glucose dyshomeostasis in the general Chinese urban adults, and these associations were exacerbated and partly mediated by PCO. Given that other pollutants were not included in this study, the effect of co-exposure of pyrethroids with multiple pollutants is necessary to be considered in future studies.

Effects of feeding variable levels of mycotoxins with or without a mitigation strategy on growth performance, gut permeability, and oxidative biomarkers in nursery pigs.

The objectives were to determine how high levels (> 2.5 mg/kg diet) of deoxynivalenol (DON), in conjunction with other naturally occurring mycotoxins (MTX) would impact growth, intestinal integrity, and oxidative status, with or without a mitigation strategy, in nursery pigs. One-hundred and five pigs (5.5 ± 0.52 kg) were randomly allotted to 35 pens and fed dietary treatments for 45 d. Treatments were factorially arranged with the inclusion of MTX being low (L-MTX; < 1 mg/kg diet) or high (H-MTX; > 2.5 mg/kg diet) in combination with no mitigation strategy or the inclusion of a mitigation strategy (Biofix® Plus, BPL; 1.5 mg/kg diet). There was no interaction between MTX level and BPL inclusion on average daily gain (ADG) or gain to feed ratio (GF), (P > 0.10). Compared to pigs fed diets containing L-MTX, feeding pigs diets containing H-MTX decreased ADG and GF (P < 0.05). The addition of BPL had no effect on ADG (P > 0.10), but improved GF (P = 0.09). There was an interaction between MTX and BPL on average daily feed intake (ADFI), where the addition of BPL had no effect on ADFI of pigs fed L-MTX diets but improved ADFI of pigs fed H-MTX diets (P = 0.09). An interaction was detected between MTX and BPL on protein oxidation as measured by plasma protein carbonyls (PC, P = 0.01), where the inclusion of BPL decreased plasma PC in pigs fed H-MTX diets to a greater extent than pigs fed the L-MTX diets. There was no interaction between MTX and BPL, or an effect of MTX or BPL on DNA damage as measured by 8-hydroxy-2'dexoxyguanosine (P > 0.10). There was no interaction between MTX and BPL, or a BPL effect on lipid damage as measured by thiobarbituic acid reactive substances (TBARS, P > 0.10), but pigs fed diets containing H-MTX exhibited lower concentrations of plasma TBARS (P = 0.07) compared to pigs fed L-MTX diets. There was no interaction between MTX and BPL, or an effect of MTX or BPL on plasma lactulose and mannitol ratio as a measure of intestinal permeability (P > 0.10). In conclusion, feeding H-MTX decreased ADG and GF, decreased plasma TBARS, but did not affect plasma 8-hydroxy-2'dexoxyguanosine or plasma LM ratio. The inclusion of a mitigation strategy improved ADFI when pigs were fed H-MTX diets and improved GF regardless of MTX level. Addition of a mitigation strategy also reduced plasma protein damage but did not affect indicators of DNA or lipid damage or affect gastrointestinal integrity.

MitoQ supplementation augments acute exercise-induced increases in muscle PGC1α mRNA and improves training-induced increases in peak power independent of mitochondrial content and function in untrained middle-aged men

The role of mitochondrial ROS in signalling muscle adaptations to exercise training has not been explored in detail. We investigated the effect of supplementation with the mitochondria-targeted antioxidant MitoQ on a) the skeletal muscle mitochondrial and antioxidant gene transcriptional response to acute high-intensity exercise and b) skeletal muscle mitochondrial content and function following exercise training. In a randomised, double-blind, placebo-controlled, parallel design study, 23 untrained men (age: 44 ± 7 years, VO2peak: 39.6 ± 7.9 ml/kg/min) were randomised to receive either MitoQ (20 mg/d) or a placebo for 10 days before completing a bout of high-intensity interval exercise (cycle ergometer, 10 × 60 s at VO2peak workload with 75 s rest). Blood samples and vastus lateralis muscle biopsies were collected before exercise and immediately and 3 h after exercise. Participants then completed high-intensity interval training (HIIT; 3 sessions per week for 3 weeks) and another blood sample and muscle biopsy were collected. There was no effect of acute exercise or MitoQ on systemic (plasma protein carbonyls and reduced glutathione) or skeletal muscle (mtDNA damage and 4-HNE) oxidative stress biomarkers. Acute exercise-induced increases in skeletal muscle peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α) mRNA expression were augmented in the MitoQ group. Despite this, training-induced increases in skeletal muscle mitochondrial content were similar between groups. HIIT-induced increases in VO2peak and 20 km time trial performance were also similar between groups while training-induced increases in peak power achieved during the VO2peak test were augmented in the MitoQ group. These data suggest that training-induced increases in peak power are enhanced following MitoQ supplementation, which may be related to the augmentation of skeletal muscle PGC1α expression following acute exercise. However, these effects do not appear to be related to an effect of MitoQ supplementation on exercise-induced oxidative stress or training-induced mitochondrial biogenesis in skeletal muscle.

Effects of aging and type 2 diabetes on cardiac structure and function: Underlying mechanisms

This study characterized long‐term changes in cardiac structure and function in a high‐fat diet/streptozotocin mouse model of aging and type 2 diabetes mellitus (T2D) and how the intersection of both conditions alters plasma metabolomics. Furthermore, we wanted to assess the possible mechanistic roles played by oxidative stress, increases in arginase activity and pro‐inflammatory cytokines levels. For this purpose, 38, 13‐month‐old C57BL/6 male mice were utilized. Control animals (n=13) were fed a regular chow for a period of 10 months. T2D (n=25) animals were provided a single injection of streptozotocin (75 mg/kg/IP) and fed a 60% high fat diet (HFD) for the same period of time. To track changes in cardiac structure and function serial echocardiography was performed. At the end of the study, blood samples were collected via a cardiac puncture and plasma samples frozen. Hearts were sectioned and allocated for either rapid freezing (biochemical studies) or fixed in formalin for histological analysis. Biochemical assays using blood and/or tissue samples included determinations for arginase activity, pro‐inflammatory cytokines, protein carbonylation, glucose tolerance tests, Western blots and plasma metabolomics. Glucose tolerance tests confirmed the development of T2D in the HFD animal group. Serial echo yielded moderate increases in cardiac mass with aging that were greater in T2D animals. Fractional shortening (figure) significantly decreased by 16 months of age in T2D animals yielding a value of 28% at 23 months vs. 40% in aged controls. Ejection fraction also significantly decreased by 16 months of age in T2D animals yielding 55% at 23 months vs. aged animals (70%). Western blots of myocardium samples documented increases in fibronectin, type III collagen and smooth muscle actin with T2D which were confirmed by immunohistochemistry. Significant increases in plasma protein carbonyls, TGF‐β1, TNF‐α, IL1β and IFN‐γ occurred with aging and further increased with T2D. Untargeted metabolomics and cheminformatics revealed clear differences in the plasma metabolome of the HFD mice vs. controls. Multiple lipid metabolites linked to insulin resistance were dysregulated, including C16:0 and C18:0 acyl carnitines (up‐modulated) and saturated and unsaturated phosphocholine‐containing lipids (up and down‐modulated). In summary, we document the development of cardiac hypertrophy with aging that is aggravated by T2D. Systolic dysfunction occurred as a late age associated event with T2D. Increases in OS markers and pro‐inflammatory cytokines occurred with aging and were aggravated with T2D. These changes were accompanied by increases in myocardial and blood arginase activity and TGF‐β1 levels which may account for the development of fibrosis and may be associated with altered plasma metabolomics.

Beneficial In Vitro Effects of a Low Myo-Inositol Dose in the Regulation of Vascular Resistance and Protein Peroxidation under Inflammatory Conditions.

Oxidative stress induces functional changes in arteries. Therefore, the effect of myo-inositol, a possible anti-inflammatory/antioxidant agent was studied on human plasma and rat thoracic arteries. Aortic rings from male Wistar rats (3 months of age) were incubated with myo-inositol (1, 10 and 100 μM, 120 min) and analyzed using the gas chromatography (GC) method. In another experiment, aortic rings were protected first with myo-inositol (1 µM, 60 min) and then subjected to a thromboxane receptor agonist (U-46619, 0.1 nM, 60 min). Therefore, these four groups under the following conditions were studied: (i) the control in the vehicle; (ii) myo-inositol; (iii) the vehicle plus U-46619; (iv) myo-inositol plus U-46619. The hemostatic parameters of human plasma and an H2O2/Fe2+ challenge for lipid and protein peroxidation were also performed. Myo-inositol was not absorbed into the pre-incubated aortic rings as measured by the GC method (0.040 µg/mg, p ≥ 0.8688). The effect of myo-inositol was more significant in the impaired arteries due to U-46619 incubation, which resulted in an improved response to acetylcholine (% Emax: 58.47 vs. 86.69), sodium nitroprusside (logEC50: −7.478 vs. −8.076), CORM-2 (% Emax: 44.08 vs. 83.29), pinacidil (logEC50: −6.489 vs. −6.988) and noradrenaline (logEC50: −7.264 vs. −6.525). This was most likely a possible response to increased nitric oxide release (×2.6-fold, p < 0001), and decreased hydrogen peroxide production (×0.7-fold, p = 0.0012). KCl-induced membrane depolarization was not modified (p ≥ 0.4768). Both the plasma protein carbonylation (×0.7-fold, p = 0.0006), and the level of thiol groups (×3.2-fold, p = 0.0462) were also improved, which was not significant for TBARS (×0.8-fold, p = 0.0872). The hemostatic parameters were also not modified (p ≥ 0.8171). A protective effect of myo-inositol was demonstrated against prooxidant damage to human plasma and rat thoracic arteries, suggesting a strong role of this nutraceutical agent on vasculature which may be of benefit against harmful environmental effects.