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Objectives: Cichorium intybus is used in traditional medicine for various diseases including heart disease. This study aimed at evaluating the chemokine receptor type 4 up-regulation and cardioprotective effects of hydroalcoholic extract of C. intybus in a rat model of ischemic reperfusion., Methods: Animals in four groups of eight rats each received vehicle or one of three doses of C. intybus (50, 100 or 200 mg/kg/d) for 14 days. Then they were subjected to 30 min of ischemia followed by 7 days of reperfusion. At the end of the experiment, blood specimens were prepared for serum assays. The level of myocardium chemokine receptor type 4 was also measured using RT-PCR., Key Findings: Cichorium intybus (CI-50) improved infarct size, episodes of the ventricular ectopic beat, ventricular tachycardia, and duration of ventricular tachycardia, QTc shortening. It also stabilized the ST segment changes and increased heart rate during ischemia. The blood pressure decreased in CI-50 group in comparison to the control and CI-200 group. C. intybus increased serum superoxide dismutase and reduced lactate dehydrogenase activity, Cardiac Troponin I and malondialdehyde levels. C. intybus led to an increase in the expression of chemokine receptor type 4., Conclusions: These findings suggest that C. intybus administration before ischemia is able to induce cardioprotective effect against ischemic reperfusion injury, probably through chemokine receptor type 4 over-expression and antioxidant activity., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Emerging evidence indicates that the pancreas serves as a major source of degrading protease activities and that uncontrolled proteolytic receptor cleavage occurs under hypertensive conditions, which leading to systemic dysfunction and end-organic damage. However, changes in pancreatic microcirculation profiles during the progression of hypertension remain unknown., Methods: Pancreatic microcirculatory blood distribution patterns and microvascular vasomotion of spontaneously hypertensive rats (SHRs) and normotensive control Wistar Kyoto rats at 5, 8, 13, and 18 weeks of age were determined. Wavelet transform analysis was performed to convert pancreatic microhemodynamic signals into time-frequency domains and construct 3-dimensional spectral scalograms. The amplitudes of characteristic oscillators including endothelial, neurogenic, myogenic, respiratory, and cardiac oscillators were compared among groups. Plasma nitrite/nitrate levels were measured using a Griess reaction. Additionally, endothelin-1, malondialdehyde, superoxide dismutase, and interleukin-6 levels were determined by enzyme-linked immunosorbent assay., Results: SHRs exhibited a reduced blood distribution pattern with progressively decreased average blood perfusion, amplitude, and frequency of microvascular vasomotion. Wavelet transform spectral analysis revealed significantly reduced amplitudes of endothelial oscillators from 8- to 18-week-old SHRs. Additionally, the blood microcirculatory chemistry complements explained the microhemodynamic profiles partially, as demonstrated by an increase in plasma nitrite/nitrate, endothelin-1, malondialdehyde, and interleukin-6 levels and a decreased superoxide dismutase level in SHRs., Conclusions: Pancreatic microcirculation profiles are abnormal in the progression of hypertension in SHRs, including a disarranged blood distribution pattern, impaired microvascular vasomotion, and reduced amplitudes of endothelial oscillators., (© The Author(s) 2020. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.)

Context: Dementia is the fifth leading cause of death in the world. Animal studies indicate that in addition to the aging process, intestinal microbiota may play an important role in the neurodegeneration process through the modulation of the gut-brain axis., Objective: A systematic review and meta-analysis was conducted to determine the effectiveness of probiotic and synbiotic supplementation on the cognitive function of individuals with dementia., Data Sources: MEDLINE, BVS, SciELO, CENTRAL, Embase, and grey literature were searched from their inception to January 2019., Study Selection: We included data from randomized clinical trials (RCTs) that addressed dementias and assessed the following outcomes: cognitive function; inflammatory, oxidative stress, and metabolic markers; nutritional status; and intestinal microbiota composition., Data Extraction: Data searches, article selection, data extraction, and risk-of-bias assessments were performed according to the Cochrane guidelines. Data were pooled by inverse-variance random-effects meta-analyses. GRADE (Grading of Recommendations Assessment, Development, and Evaluations) was used to assess the quality of evidence., Results: Data from 3 RCTs involving 161 individuals with Alzheimer's disease receiving Lactobacillus and Bifidobacterium strains showed no beneficial effect of probiotic supplementation on cognitive function (standardized mean difference, 0.56; 95%CI: -0.06 to 1.18), with very low certainty of evidence. However, probiotic supplementation improved plasma triglycerides, very-low-density lipoprotein cholesterol, insulin resistance, and plasma malondialdehyde. No RCTs included synbiotic supplementation or assessed microbiota composition., Conclusion: Current evidence regarding the use of probiotics and synbiotics for individuals with dementia is insufficient to support their clinical application., Systematic Review Registration: PROSPERO registration no: CRD42018116148., (© The Author(s) 2020. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The pathogenesis and etiology of schizophrenia (SCZ) remains unclear. Accumulating studies showed that complex interrelationships between brain-derived neurotrophic factor (BDNF) and an imbalanced redox system has a crucial role in the psychopathology of SCZ. However, the influence of the interrelationships of BDNF and superoxide dismutase (SOD) on cognitive impairment and clinical symptomatology in drug-naive first-episode (DNFE) SCZ patients has not been studied thoroughly. Serum BDNF levels, plasma total SOD, manganese-SOD (Mn-SOD), copper/zinc-containing SOD (CuZn-SOD) activities, and malondialdehyde (MDA) levels were measured in 327 DNFE patients with SCZ and 391 healthy controls. Cognitive functions were measured using the Repeatable Battery for the Assessment of Neuropsychological status (RBANS) and clinical symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS). Compared with the controls, the DNFE patients had increased activities of total SOD and CuZn-SOD, and reduced levels of BDNF and MDA. BDNF levels were positively correlated with CuZn-SOD activity in patients. In addition, we found that elevated Mn-SOD and CuZn-SOD activities were related to PANSS depression factor. Moreover, an interactive effect of BDNF levels and Mn-SOD activity was associated with attentional index score in the patients. Therefore, our findings suggested that interrelationships between BDNF and antioxidant mechanisms might underlie the pathological mechanisms of cognitive impairments and symptomatology in the DNFE patients with SCZ., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Electroconvulsive therapy (ECT) is an effective option for treatment-resistant bipolar disorder (trBD). However, the mechanisms of its effect are unknown. Oxidative stress is thought to be involved in the underpinnings of BD. Our study is the first, to our knowledge, to report the association between notable oxidative stress parameters (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], catalase [CAT], and malondialdehyde [MDA]) levels and ECT response in trBD patients., Methods: A total 28 trBD patients and 49 controls were recruited. Six-week ECT and naturalistic follow-up were conducted. SOD, GSH-Px, CAT, and MDA levels were measured by enzyme-linked immunosorbent assay, and the 17-item Hamilton Depression Rating Scale and Young Mania Rating Scale were administered at baseline and the end of the 6th week. MANCOVA, ANCOVA, 2 × 2 ANCOVA, and a multiple regression model were conducted., Results: SOD levels were lower in both trBD mania and depression (P = .001; P = .001), while GSH-Px (P = .01; P = .001) and MDA (P = .001; P = .001) were higher in both trBD mania and depression compared with controls. CAT levels were positively associated with 17-item Hamilton Depression Rating Scale scores in trBD depression (radjusted  = 0.83, P = .005). MDA levels in trBD decreased after 6 weeks of ECT (P = .001). Interestingly, MDA levels decreased in responders (P = .001) but not in nonresponders (P > .05)., Conclusions: Our study indicates that decreased SOD could be a trait rather than a state in trBD. Oxidative stress levels are associated with illness severity and ECT response. This suggests that the mechanism of oxidative stress plays a crucial role in the pathophysiology of trBD., (© The Author(s) 2020. Published by Oxford University Press on behalf of CINP.)

We developed a robust analytical method for quantification of malondialdehyde (MDA) in urine and serum samples using dansylhydrazine (DH) as a derivatizing reagent. The derivatization procedure was partially carried out using an autosampler injection program to minimize errors associated with the low-volume addition of reagents and was optimized to yield a stable hydrazone derivative of MDA and its labeled d2-MDA analogue. The target MDA-DH derivatives were separated on an Agilent Zorbax Eclipse Plus Phenyl-Hexyl (3.0 × 100 mm, 3.5 μm) column. The mass-to-charge ratios of the target derivatives [(M+H)+ of 302 and 304 for MDA-DH and d2-MDA-DH, respectively] were analyzed in single ion monitoring mode using a single quadrupole mass spectrometer operated under positive electrospray ionization. The method limits of quantification were 5.63 nM (or 0.405 ng/mL) for urine analysis and 5.68 nM (or 0.409 ng/mL) for serum analysis. The quantification range for urine analysis was 5.63-500 nM (0.405-36.0 ng/mL) while the quantification range for serum analysis was 5.68-341 nM (0.409-24.6 ng/mL). The method showed good relative recoveries (98-103%), good accuracies (92-98%), and acceptable precisions (relative standard deviations 1.8-7.3% for inter-day precision; 1.8-6.1% for intra-day precision) as observed from the repeat analysis of quality control samples prepared at different concentrations. The method was used to measure MDA in individual urine samples (n = 287) and de-identified archived serum samples (n = 22) to assess the overall performance of the method. The results demonstrated that our method is capable of measuring urinary and serum levels of MDA, allowing its future application in epidemiologic investigations., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: Platelet-derived growth factor (PDGF) promotes liver collagen deposition, acting on hepatic stellate cells. Despite this, low serum PDGF levels were reported in chronic hepatitis C or B infection, although some studies yield the opposite result. Since PDGF may be related not only to fibrosis but also with vascular, neuronal or muscle disease, it is important to analyze its behavior in alcoholics., Methods: In total, 17 controls and 62 alcoholic patients consecutively admitted to the hospitalization unit of the Internal Medicine Service were included. We determined serum levels of PDGF C, routine laboratory evaluation, tumor necrosis factor-α, interleukin (IL)-6 and IL-8 and malondialdehyde (MDA) levels. We analyzed the relationships between PDGF and liver function, ethanol intake and inflammatory reaction by both univariate and multivariate analysis to discern which variables PDGF levels depend on., Results: Serum PDGF levels were significantly lower among patients (675 ± 466 pg/ml) than among controls (1074 ± 337 pg/ml; Z = 3.70; P < 0.001), and even lower among cirrhotics (549 ± 412 among cirrhotics vs 778 ± 487 among non-cirrhotics; Z = 2.33; P = 0.02). PDGF levels showed a direct correlation with prothrombin activity (ρ = 0.50; P < 0.001), platelet count (ρ = 0.44; P < 0.001) and inverse ones with bilirubin (ρ = -0.39; P = 0.002), IL-6 (ρ = -0.33; P = 0.016), IL-8 (ρ = -0.47; P < 0.001), and MDA levels (ρ = -0.44; P < 0.001). By multivariate analysis, only prothrombin activity and platelet count were independently related to PDGF., Conclusion: PDGF-C levels are decreased in alcoholics, especially among cirrhotics. Multivariate analysis discloses that only prothrombin activity and platelet count are independently related to PDGF-C levels., (© The Author(s) 2020. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Background: In renal transplant recipients (RTRs), cardiovascular mortality is the most common cause of long-term renal graft loss. Oxidative stress (OS) has been associated with cardiovascular disease and is known to be enhanced in RTRs. We aimed to prospectively investigate whether the concentration of the OS biomarker malondialdehyde (MDA) is associated with long-term risk of cardiovascular mortality in a large cohort of RTRs., Methods: The plasma MDA concentration was measured using the thiobarbituric acid reaction assay in 604 extensively phenotyped RTRs with a functioning allograft for ≥1 year. The association between MDA and cardiovascular mortality was assessed using Cox proportional hazard regression analyses in the overall cohort and within subgroups according to significant effect modifiers., Results: Median circulating MDA concentration at baseline was 5.38 [interquartile range (IQR) 4.31-6.45] μmol/L. During a follow-up period of 6.4 (IQR 5.6-6.8) years, 110 (18%) RTRs died, with 40% of deaths due to cardiovascular causes. MDA concentration was significantly associated with the risk for cardiovascular mortality {hazard ratio [HR] 1.31 [95% confidence interval (CI) 1.03-1.67] per 1-SD increment}, independent of adjustment for potential confounders, including renal function, immunosuppressive therapy, smoking status and blood pressure. The association between MDA concentration and the risk for cardiovascular mortality was stronger in RTRs with relatively lower plasma ascorbic acid concentrations [≤42.5 µmol/L; HR 1.79 (95% CI 1.30-2.48) per 1-SD increment] or relatively lower estimated glomerular filtration rates [≤45 mL/min/1.73 m2; HR 2.09 (95% CI 1.45-3.00) per 1-SD increment]., Conclusions: Circulating MDA concentration is independently associated with long-term risk for cardiovascular mortality, particularly in RTRs with relatively lower ascorbic acid concentrations or renal function. Further studies are warranted to elucidate whether OS-targeted interventions could decrease cardiovascular mortality in RTRs., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

The purpose of this study was to set up a beagle dog model, for radiation-induced lung injury, that would be able to supply fresh lung tissues in the different injury phases for research into oxidative stress levels and mitochondrial gene expression. Blood serum and tissues were collected via CT-guided core needle biopsies from dogs in the various phases of the radiation response over a 40-week period. Levels of reactive oxygen species (ROS) and manganese superoxide dismutase 2 (MnSOD) protein expression in radiation-induced lung injury were determined by in situ immunocytochemistry; malondialdehyde (MDA) content and reductase activity in the peripheral blood were also tested; in addition, the copy number of the mitochondrial DNA and the level of function of the respiratory chain in the lung tissues were assessed. ROS showed dynamic changes and peaked at 4 weeks; MnSOD was mainly expressed in the Type II alveolar epithelium at 8 weeks; the MDA content and reductase activity in the peripheral blood presented no changes; the copy numbers of most mitochondrial genes peaked at 8 weeks, similarly to the level of function of the corresponding respiratory chain complexes; the level of function of the respiratory chain complex III did not peak until 24 weeks, similarly to the level of function of the corresponding gene Cytb. Radiation-induced lung injury was found to be a dynamically changing process, mainly related to interactions between local ROS, and it was not associated with the levels of oxidative stress in the peripheral blood. Mitochondrial genes and their corresponding respiratory chain complexes were found to be involved in the overall process., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Objectives: Aldehyde dehydrogenase 2 activity is associated with cardioprotection. Individuals carrying an East Asian variant of the ALDH2 genotype (ALDH2*2) have significantly reduced aldehyde dehydrogenase 2 activity. No previous studies have determined the effect of the ALDH2*2 genotype on cardioprotective results after coronary artery bypass grafting (CABG)., Methods: In total, 207 patients who underwent selective off-pump CABG were prospectively enrolled. Their baseline characteristics and clinical results were collected. Preoperative and postoperative circulating oxidative stress levels (serum malondialdehyde adducts and hydroxynonenal adducts) were measured. After genotyping, the oxidative stress levels and clinical results were compared between the ALDH2*2 carriers and non-carriers., Results: ALDH2*2 carriers exhibited higher levels of malondialdehyde (P = 0.02) and hydroxynonenal (P = 0.03) adducts after CABG. ALDH2*2 carriers had higher postoperative troponin I levels (P = 0.01) and 24-h inotropic scores (P = 0.02). The intensive care unit time (P = 0.03) and postoperative length of stay (P = 0.03) were longer in ALDH2*2 carriers. The postoperative pulmonary infection rate was higher (P = 0.03) in ALDH2*2 carriers., Conclusions: Patients with the ALDH2*2 genotype had higher postoperative oxidative stress levels and poorer clinical results after CABG. Special cardioprotective techniques should be considered for patients with a history of 'facial flushing' when performing CABG.

Extensive research has been focused on radiation-induced brain injury. Animal and human studies have shown that flavonoids have remarkable toxicological profiles. This study aims to investigate the neuroprotective effects of quercetin in an experimental radiation-induced brain injury. A total of 32 adult male Wistar-Albino rats were randomly divided into four groups (control, quercetin, radiation, and radiation+quercetin groups, with eight rats in each group). Doses (50 mg/kg) of quercetin were administered to the animals in the quercetin and radiation+quercetin groups; radiation and radiation+quercetin groups were exposed to a dose of 20 Gy to the cranium region. Tissue samples, and biochemical levels of tissue injury markers in the four groups were compared. In all measured parameters of oxidative stress, administration of quercetin significantly demonstrated favorable effects. Both plasma and tissue levels of malondialdehyde and total antioxidant status significantly changed in favor of antioxidant activity. Histopathological evaluation of the tissues also demonstrated a significant decrease in cellular degeneration and infiltration parameters after quercetin administration. Quercetin demonstrated significant neuroprotection after radiation-induced brain injury. Further studies of neurological outcomes under different experimental settings are required in order to achieve conclusive results.

This study aims to investigate the antioxidant effect of aromatic volatiles of three common aromatic plants, Lavandula dentata, Mentha spicata, and M. piperita. In this study, kunming mice subjected to low oxygen condition were treated with the volatiles emitted from these aromatic plants through inhalation administration. Then the blood cell counts, and the activities and gene expressions of antioxidant enzymes in different tissues were tested. The results showed that low oxygen increased the counts of red blood cells, white blood cells, and blood platelets of mice, and aromatic volatiles decreased their counts. Exposure to aromatic volatiles resulted in decreases in the malonaldehyde contents, and increases in the activities and gene expressions of superoxide dismutase, glutathione peroxidase, and catalase in different tissues under low oxygen. In addition, as the main component of aromatic volatiles, eucalyptol was the potential source that imparted positive antioxidant effect.

HIV- and highly active antiretroviral therapy (HAART)-associated elevations in oxidative stress likely play a role in incomplete immune reconstitution, opportunistic infections and non-AIDS co-morbidities. We aimed to test the hypothesis that children living with HIV exhibit elevated markers of oxidative stress and reduced antioxidant profiles and that HAART-therapy will exacerbate these differences. HIV-positive HAART-naïve (n = 50) and HAART-treated (n = 50) and HIV-negative control (n = 50) participants, 3-15 years of age, were recruited from Black Lion Hospital in Ethiopia. Serum malondialdehyde (MDA) and bilirubin were higher and vitamin C and zinc were lower in HAART-naïve and HAART-treated compared with HIV-negative subjects and higher in HAART-treated compared with HAART-naïve subjects. Uric acid was higher in HAART-naïve compared with HAART-treated and HIV-negative subjects. Differences in MDA and several antioxidants were also observed across treatment regimens. Thus, children living with HIV exhibited systemic elevations in oxidative stress and reduction in antioxidants, which are exacerbated with HAART therapy., (© The Author [2016]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Aims: Alcoholic hepatitis is a severe complication of alcoholism, associated with high short-term mortality. Although pathogenesis remains obscure, it is generally accepted that lipopolysaccharide-induced cytokine secretion with further generation of reactive oxygen species (ROS) play outstanding roles. Prognosis is uncertain, and the usually employed prognostic scores do not include variables related to ROS generation. Therefore, this study was performed to assess short-term prognostic value of cytokines, nutritional status, different scores [Maddrey, model for end-stage liver disease (MELD), albumin, bilirubin, INR, creatinine index (ABIC), Lille, Glasgow, MELD-Na, Child-Pugh] and malondialdehyde (MDA, as an indicator of lipid peroxidation) at admission and after 1 week, among patients affected by severe acute alcoholic hepatitis (Maddrey index >32)., Methods: Sixty-two patients affected by severe acute alcoholic hepatitis, for whom we calculated Maddrey, MELD, ABIC, Lille, Glasgow, MELD-Na, Child-Pugh, and determined serum MDA and interleukin (IL)-6, IL-8, IL-4, tumor necrosis factor alpha and interferon gamma levels at admission and after 1 week., Results: Twenty-four patients died during the follow-up period. MDA showed a better prognostic accuracy than the aforementioned scores, both at admission and after 1 week., Conclusion: Our study supports the importance of including MDA assessment in the prognostic evaluation of patients with alcoholic hepatitis., Short Summary: Alcoholic hepatitis is associated with high short-term mortality. Although not included in prognostic scores, lipid peroxidation plays an outstanding role in its pathogenesis. We found that malondialdehyde levels showed a better prognostic accuracy than the usually employed scores. Therefore, it should be included in the prognostic evaluation of these patients., (© The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Objectives: The purpose of this study is to clarify the relationship between systemic sclerosis (SSC) and oxidative stress markers in blood., Methods: We conducted a systematic literature search of databases, including PubMed and Embase, for studies reporting circulating oxidative stress markers in patients with SSC and controls published from 1980 to December 2015. Standardized mean differences (SMDs) and 95% confidence intervals (95%CI) were calculated., Results: Of the 1076 articles initially retrieved, 47 were included in our meta-analysis including 12 oxidative stress markers. The concentrations of nitric oxide (SMD = 0.77; 95%CI: 0.18, 1.36; p = 0.01), malondialdehyde (SMD =1.63; 95%CI: 1.03, 2.24; p = 0.000), asymmetric dimethylarginine (SMD = 0.51; 95%CI: 0.12, 0.91; p = 0.011), and ROOH (SMD = 3.37; 95%CI: 0.28, 6.46; p = 0.033) in the blood of patients with SSC were higher than those of the control group, whereas the concentrations of superoxide dismutase (SMD = -1.11; 95%CI: -1.57, -0.65; p = 0.000) and vitamin C (SMD = -1.12; 95%CI: -1.51, -0.73; p = 0.000) were lower than in the control group., Conclusions: The oxidative stress markers in blood for patients with SSC were aberrant, indicating the imbalanced states of oxidation and antioxidation in SSC.

Introduction: Our objective was to investigate the relationships between secondhand smoke (SHS) exposure and oxidative stress in a group of youth and adolescents with elevated body mass index., Methods: Participants in this cross sectional study were healthy nonsmoking youth and adolescents ages 9 to 18 years old. Three-quarters of the participants were either overweight or obese. SHS exposure was determined by survey and hair nicotine level. Markers of oxidation were total antioxidant capacity and protein malondialdehyde adducts (MDA)., Results: Ninety subjects were studied; adequate hair samples were available for 86. The mean hair nicotine level was 0.75ng/mg, the median was 0.58ng/mg and the range was 0.09-2.88ng/mg. There was a significant relationship between MDA and the three survey questions regarding smoke exposure ([mother smokes, r = 0.29, P = .006], [smoker lives in the home, r = 0.31, P = .004], and [number of smokers in the home, r = 0.36, P = .002]). There was a significant positive relationship between log-hair nicotine and MDA (Pearson r = 0.233, P = .031), which remained significant after controlling for age, sex, race, and method of insurance. No relationship was found between log-hair nicotine and total antioxidant capacity. However, there was a significant relationship between number of smokers in the home (r = 0.24, P = .042) and total antioxidant capacity., Conclusions: We have demonstrated a significant positive relationship hair nicotine level and MDA in a group of youth with a high proportion of overweight/obese subjects., Implications: We have shown a significant relationship between objectively measured SHS exposure and one marker of oxidative stress in a sample of youth and adolescents with a high proportion of overweight/obese subjects, and who were nonsmokers with relatively low tobacco exposure. This finding remains significant after controlling for age, sex, race, and type of medical insurance. Since the cardiovascular effects of SHS exposure are related to oxidative stress, this finding adds to our knowledge that the sequence of deleterious effects of tobacco exposure on the cardiovascular system begins long before clinical disease is evident., (© The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The aim of this study was to investigate the cardioprotective effect of salvianolic acid B (Sal B) on acute myocardial infarction (AMI) in rats and its potential mechanisms., Methods: The AMI model was established in rats to study the effect of Sal B on AMI. Haematoxylin-eosin (HE) staining was used to evaluate the pathological change in AMI rats. Immunofluorescence and TUNEL staining were used to detect autophagy and apoptosis of myocardial cells in hearts of AMI rats, respectively. Protein expression of apoptosis-related, autophagy-related and angiogenesis-related proteins were examined by Western blot., Key Findings: Sal B attenuated myocardial infarction significantly compared with that of the model group. Rats administered with Sal B showed higher inhibition rate of infarction and lower infarct size than those of the model group. Moreover, Sal B decreased the serum levels of creatine kinase, lactate dehydrogenase and malondialdehyde, while increased such level of superoxide dismutase significantly compared with those of the model group. Sal B inhibited the expression of Bax, cleaved caspase-9 and cleaved PARP, while promoted the expression of Bcl-2, LC3-II, Beclin1 and VEGF., Conclusions: Sal B has cardioprotective effect on AMI and Sal B may be a promising candidate for AMI treatment., (© 2016 Royal Pharmaceutical Society.)

Introduction: Physical activity has been found to be related with many health benefits. Our aim was to investigate the effect of chronic moderate exercise from acute stress on nicotine and cigarette smoke exposed rats., Methods: Male Sprague Dawley rats (200-250g, n = 48) were divided into 6 groups as non-exercised, exercised, smoke exposed, smoke exposed and exercised, nicotine applied, and nicotine applied and exercised. Nicotine bitartarate was applied intraperitoneally (0.1mg/kg/day) for 5 weeks, and cigarette smoke was exposed in a ventilated chamber. After 1 week of nicotine application or smoke exposure, moderate exercise training protocol was applied to exercise groups. At the end of the experiments, acute stress induction was made to all groups by electric foot shock. Holeboard tests were performed before and after the experiments. Biochemical and histological analyses were performed in lung, liver, colon, stomach, and gastrocnemius tissues., Results: Malondialdehyde levels were increased in all tissues of smoke exposed group (p < .05-.01) except gastrocnemius tissue compared to non-exercised group and were decreased with exercise (p < .05-.001). Myeloperoxidase levels were increased in lung, liver and colon tissues of smoke exposed group (p < .05-.001) and liver and colon tissues of nicotine applied rats (p < .01-.001) and decrease with exercise in liver and colon tissues of both smoke exposed or nicotine applied groups (p < .05-.01). In all tissue samples, increased histological injury scores (p < .05-.001) decreased significantly with exercise (p < .01-.001)., Conclusion: Biochemical parameters and histological scoring indicated increased tissue injury due to nicotine application and cigarette smoke exposure and exercise training ameliorated these effects in most of the tissues of acute stress induced rats., (© The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Ischaemia/reperfusion (I/R) injury of the lungs contributes to pulmonary dysfunction after cardiac surgery with cardiopulmonary bypass (CPB), leading to increased morbidity and mortality of patients. This study investigated the value of controlled lung reperfusion strategies on lung ischaemia-reperfusion injury in a porcine CPB model., Methods: Pigs were subjected to routine CPB for 120 min with 60 min of blood cardioplegic cardiac arrest (CCA). Following CCA, the uncontrolled reperfusion (UR, n = 6) group was conventionally weaned from CPB. Two groups underwent controlled lung reperfusion strategies (CR group: controlled reperfusion conditions, n = 6; MR group: controlled reperfusion conditions and modified reperfusate, n = 6) via the pulmonary artery before CPB weaning. Sham-operated pigs (n = 7) served as controls. Animals were followed up until 4 h after CPB. Pulmonary function, haemodynamics, markers of inflammation, endothelial injury and oxidative stress as well as morphological lung alterations were analysed., Results: CPB (UR group) induced deterioration of pulmonary function (lung mechanics, oxygenation index and lung oedema). Also, controlled lung reperfusion groups (CR and MR) presented with pulmonary dysfunction after CPB. However, compared with UR, controlled lung reperfusion strategies (CR and MR) improved lung mechanics and reduced markers of oxidative stress, but without alteration of haemodynamics, oxygenation, inflammation, endothelial injury and lung morphology. Both controlled reperfusion groups were similar without relevant differences., Conclusion: Controlled lung reperfusion strategies attenuated a decrease in lung mechanics and an increase in oxidative stress, indicating an influence on CPB-related pulmonary injury. However, they failed to avoid completely CPB-related lung injury, implying the need for additional strategies given the multifactorial pathophysiology of postoperative pulmonary dysfunction., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Disturbances in both circadian rhythms and oxidative stress systems have been implicated in the pathophysiology of bipolar disorder (BD), yet no studies have investigated the relationship between these systems in BD. We studied the impact of circadian rhythm disruption on lipid damage in 52 depressed or euthymic BD females, while controlling for age, severity of depressive symptoms and number of psychotropic medications, compared to 30 healthy controls. Circadian rhythm disruption was determined by a self-report measure (Biological Rhythm Interview of Assessment in Neuropsychiatry; BRIAN), which measures behaviours such as sleep, eating patterns, social rhythms and general activity. Malondialdehyde (MDA) levels were measured as a proxy of lipid peroxidation. We also measured the activity of total and extracellular superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST). Multiple linear regressions showed that circadian rhythm disturbance was independently associated with increased lipid peroxidation in females with BD (p < 0.05). We found decreased extracellular SOD (p < 0.05), but no differences in total SOD, CAT or GST activity between bipolar females and controls. Circadian rhythms were not associated with lipid peroxidation in healthy controls, where aging was the only significant predictor. These results suggest an interaction between the circadian system and redox metabolism, in that greater disruption in daily rhythms was associated with increased lipid peroxidation in BD only. Antioxidant enzymes have been shown to follow a circadian pattern of expression, and it is possible that disturbance of sleep and daily rhythms experienced in BD may result in decreased antioxidant defence and therefore increased lipid peroxidation. This study provides a basis for further investigation of the links between oxidative stress and circadian rhythms in the neurobiology of BD.

Bacterial meningitis is a common cause of morbidity and mortality in children. The oxidative stress in bacterial meningitis is barely determined. Forty children with bacterial meningitis were studied for their oxidants and antioxidants status in serum and cerebrospinal fluid. Fever (95%) was commonest presentation followed by seizure and vomiting. Neck rigidity and Kernig's sign were present in 37.5% and 27.5% cases, respectively. Plasma and cerebrospinal fluid malondialdehyde, protein carbonyl and nitrite levels were significantly raised in cases (p < 0.001). Plasma and cerebrospinal fluid ascorbic acid, glutathione and superoxide dismutase levels were significantly decreased in children with septic meningitis (p < 0.001). Significantly elevated malondialdehyde, nitrite and protein carbonyl levels reflect increased oxidative stress, whereas decreased concentrations of glutathione, ascorbic acid and superoxide dismutase indicates utilization of the antioxidants in septic meningitis. Thus, changes in oxidants and antioxidants observed suggest production of reactive oxygen species and their possible role in pathogenesis of septic meningitis.

Objective: To investigate the relationship between oxidative stress and smoking and development of RA., Methods: A case-control study was conducted in treatment-naïve early-onset RA patients and healthy controls, matched by age, gender and current smoking habit. Plasma lipid hydroperoxides (LOOH), carbonyl protein (CP) and malonyldialdehyde (MDA) levels were measured to estimate oxidative stress. Smoking exposure was quantified in pack-years. The presence of an interaction between oxidative stress and smoking exposure was investigated using three measures of additive interaction: relative excess risk due to the interaction (RERI), attributable proportion due to the interaction (AP) and the synergy index (S)., Results: A total of 65 RA patients and 65 healthy controls were included. Statistically significant differences were observed in RA-related variables, age, BMI and smoking dose between cases and controls. Plasma LOOH and CP levels were associated with RA risk, which was more prominent for LOOH levels >27.9 µM [odds ratio (OR) 18.8] and CP levels >64.3 µM (OR 24.9). A reverse association was observed between MDA levels and RA risk, OR 6.4 for MDA levels <8.5 µM. Having >20 pack-years increased risk for RA with an OR of 19.7. The interaction between smoking and oxidative stress increased RA risk significantly, and RERI between LOOH, CP or MDA and smoke exposure were 8.2, 5.0 and 51.5, respectively., Conclusion: These data suggest that the interaction between oxidative stress and smoking increases RA risk.

Patients with chronic kidney disease (CKD) have signs of genomic instability and, as a consequence, extensive genetic damage, possibly due to accumulation of uraemic toxins, oxidative stress mediators and other endogenous substances with genotoxic properties. We explored factors associated with the presence and background levels of genetic damage in CKD. A cross-sectional study was performed in 91 CKD patients including pre-dialysis (CKD patients; n = 23) and patients undergoing peritoneal dialysis (PD; n = 33) or haemodialysis (HD; n = 35) and with 61 healthy subjects, divided into two subgroups with the older group being in the age range of the patients, serving as controls. Alkaline comet assay and cytokinesis-block micronucleus assay in peripheral blood lymphocytes were used to determine DNA and chromosome damage, respectively, present in CKD. Markers of oxidative stress [malondialdehyde (MDA), advanced glycation end products (AGEs), thiols, advanced oxidation protein products and 8-hydroxy-2'-deoxyguanosine] and markers of inflammation (C-reactive protein, interleukin-6 and tumour necrosis factor alpha) were also measured. Micronucleus (MN) frequency was significantly higher (P < 0.05) in the CKD group (46±4‰) when compared with the older control (oC) group (27.7±14). A significant increase in MN frequency (P < 0.05) was also seen in PD patients (41.9±14‰) versus the oC group. There was no statistically significant difference for the HD group (29.7±15.6‰; P = NS) versus the oC group. Comet assay data showed a significant increase (P < 0.001) of tail DNA intensity in cells of patients with CKD (15.6±7%) with respect to the total control (TC) group (11±1%). PD patients (14.8±7%) also have a significant increase (P < 0.001) versus the TC group. Again, there was no statistically significant difference for the HD group (12.5±3%) compared with the TC group. Patients with MN values in the upper quartile had increased cholesterol, triglycerides, AGEs and MDA levels and lower albumin levels. Multiple logistic regression analysis showed that male gender, diabetes and treatment modality were independently associated with higher levels of DNA damage. Our results suggest that oxidative stress, diabetes, gender and dialysis modality in CKD patients increased DNA and chromosome damage. To confirm these data, prospective clinical trials need to be performed.

Objectives: In our study, we aimed to investigate the anti-inflammatory mediator effects of budesonide (BS), an inhaled corticosteroid and interleukin-10 (IL-10) on a pulmonary contusion in an experimental rat model in which an isolated bilateral pulmonary contusion was created by blunt thoracic trauma., Methods: Fifty-five male Sprague-Dawley rats were used in the study. Sham, control, BS and IL-10 groups were created. A pulmonary contusion was created by performing isolated blunt thoracic trauma in all groups except for the sham group. The trauma's severity was determined as 1.45 J. BS and IL-10 were administered orogastrically to the respective groups 30 min before trauma, and orogastrically and intraperitoneally, respectively, on the first and second days after the trauma. Only the blunt thoracic trauma was performed for the control group. SatO(2), PaO(2) and PaCO(2), blood glutathione, malondialdehyde (MDA) and tumour necrosis factor-α (TNFα) values were recorded on the zeroth, first, second and third days. The histopathological examination and the bronchoalveolar lavage cell count were performed on pulmonary tissues., Results: Blood gas analysis revealed that SatO(2) and PaO(2) values on the first and second days were significantly lower in the control, BS and IL-10 groups compared with the sham group (P < 0.05). The SatO(2) and PaO(2) values on the third day in the BS and IL-10 groups were higher than in the control group (P < 0.05). The mean MDA in the control group was higher than in the sham, BS and IL-10 groups (P < 0.05). The mean TNFα in the control group was higher than in the sham, BS and IL-10 groups (P < 0.05). Pulmonary pathology scoring in the control group was observed to be higher than in the sham, BS and IL-10 groups (P < 0.05)., Conclusion: In this rat experiment model in which an isolated pulmonary contusion was created by blunt trauma, BS and IL-10 were observed to reduce contusion severity in the lung and minimize the inflammatory reaction.

Aims: The importance of oxidized low-density lipoprotein (oxLDL) has been implicated in the process of plaque rupture. However, few previous studies demonstrated the relationship between plaque morphology and oxLDL. We evaluated the relationship between coronary plaque vulnerability assessed by optical coherence tomography (OCT) and circulating malondialdehyde-modified low-density lipoprotein (MDA-LDL)., Methods and Results: OCT was used to determine plaque vulnerability in 102 patients with acute coronary syndrome (ACS; n = 53) and stable angina pectoris (SAP; n = 49). Circulating levels of MDA-LDL were measured by using enzyme-linked immunosorbent assay. Thin-cap fibroatheromas (TCFAs; defined as lipid-rich with plaque cap thickness <65 μm) were detected more frequently in ACS than in SAP (83% vs. 16%, P < 0.001). The circulating levels of MDA-LDL were significantly higher in patients with ACS compared with SAP (P = 0.008). The levels of MDA-LDL were significantly higher in SAP patients with TCFA than those with non-TCFA (P < 0.001). Although the levels of MDA-LDL were not significant between ACS patients with TCFA and those with non-TCFA, patients with ruptured TCFA had higher levels of MDA-LDL compared with those with morphologically intact TCFA (P = 0.023). MDA-LDL levels were associated with the presence of TCFA (odds ratio, 1.45 per 10-unit increment of MDA-LDL; 95% CI, 1.24-1.68; P< 0.001) in multivariable logistic regression analysis., Conclusion: Circulating MDA-LDL levels might be associated with the presence of TCFA in the culprit lesion.

Background: Paraoxonase 1 (PON1) is a serum high-density lipoprotein-bound enzyme with antioxidant function. It hydrolyses lipid peroxides, protecting low-density lipoproteins from oxidative modifications. Patients with psoriasis are at greater risk of oxidative stress, which is associated with abnormal plasma lipid metabolism., Objectives: In this study, association of the PON1 55 M allele with serum arylesterase (ARE) activity, malondialdehyde (MDA), lipid profiles and psoriasis was investigated., Methods: The present case-control study consisted of 100 patients with psoriasis with and without cardiovascular diseases (mean age 35·3 years) and 100 sex- and age-matched unrelated healthy controls (mean age 35·7 years) from the population of western Iran. The PON1 55 Met>Leu polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism. Serum ARE activity, MDA, and lipid and apolipoprotein levels were determined spectrophotometrically, by high-performance liquid chromatography and by enzyme assay, respectively., Results: The presence of the PON1 55 M allele was found to be associated with psoriasis (odds ratio = 1·96, P = 0·017). The patients with psoriasis with the PON1 M (M/L + M/M) allele had higher MDA levels (4·12 ± 0·88 vs. 2·24 ± 0·55 μmol L(-1) , P < 0·001), apolipoprotein B (APOB)/APOA1 ratio (0·91 ± 0·66 vs. 0·66 ± 0·35, P = 0·004), APOB (111 ± 38·7 vs. 88·3 ± 22·5 mg mL(-1) , P = 0·001) and lipoprotein(a) [LP(a)] (21·9 ± 18·4 vs. 15·8 ± 16·6 mg mL(-1) , P = 0·034), but lower ARE activity (39·6 ± 11 vs. 45·9 ± 11·8 U mL(-1) , P = 0·031) than the control subjects. ARE activity showed a significant positive correlation with APOA1 and a negative correlation with MDA concentration in patients with psoriasis., Conclusions: The PON1 55 M allele is a risk factor for psoriasis. Carriers of this allele have high levels of MDA, APOB and LP(a), a high APOB/APOA1 ratio and low ARE activity. These results indicate that oxidative stress, impairment of the antioxidant system and abnormal lipid metabolism may play a role in the pathogenesis and progression of psoriasis and its related complications. These data suggest that patients with psoriasis are more susceptible to vascular diseases., (© 2012 The Authors. BJD © 2012 British Association of Dermatologists.)

Background: It has been shown that there is an increase in oxidative stress in polycystic ovary syndrome (PCOS). Statins are considered to have a pleiotropic effect other than their lipid-lowering effect. These effects may be mediated in part by reducing oxidative stress., Methods: This randomized, double-blind, placebo-controlled study was conducted to assess the effect of atorvastatin on serum malondialdehyde (MDA) concentrations as a marker of oxidative stress in patients with PCOS. Forty medication-naïve patients with PCOS were randomized to either atorvastatin 20 mg daily or placebo for 3 months. A 3-month extension study for both groups of patients was undertaken with metformin 1500 mg daily after completing initial 3 months of atorvastatin or placebo., Results: There was a significant decrease of MDA concentrations with atorvastatin [mean (sem)] [0.29 (0.04) vs. 0.25 (0.02) μmol/liter; P < 0.01] compared with placebo [0.28 (0.02) vs. 0.29 (0.12) μmol/liter; P = 0.52]. Three months treatment with metformin resulted in further reduction of MDA levels with atorvastatin compared with baseline [0.25 (0.02) baseline vs. 0.23 (0.03) μmol/liter for atorvastatin treated; P = 0.02]. There was also a significant correlation between the reduction in MDA with a reduction in high-sensitivity C-reactive protein (r = 0.71, P < 0.01), an increase in 25-hydroxyvitamin D (25OHD; r = -0.68, P = 0.02), and a reduction in testosterone levels (r = 0.63, P = 0.01). Multiple linear regression analysis revealed Δ25OHD, ΔC-reactive protein, and Δtestosterone were independent predictors of changes in MDA after atorvastatin treatment. No correlation was observed between the reductions in serum MDA concentrations with changes in the lipid parameters., Conclusions: Twelve weeks of atorvastatin led to a significant reduction in oxidative stress as determined by MDA concentrations among patients with polycystic ovary syndrome that was independently predicted by changes in testosterone, 25OHD, and high-sensitivity C-reactive protein.

Objectives: Gouty arthritis is characterized by intense, acute inflammatory reactions that occur in response to articular deposits of monosodium urate crystals. In this study we have assessed the effects of the flavonoid, quercetin, on monosodium urate crystal-induced inflammation in rats, an experimental model for gouty arthritis., Methods: Gouty arthritis was induced by intra-articular injection of monosodium urate crystal suspension inside the ankle joint of the rat right hind limb. Circumference was assessed at 2, 4, 8, 12, 24, and 48 h after monosodium urate crystal injection. Histopathological analysis of joint synovial tissue, inflammatory mediator levels, lipid peroxidation, and antioxidant status in serum, liver and joint synovial tissue were determined in control and monosodium urate crystal-treated rats at the end of experiment., Key Findings: Quercetin treatment attenuated oedema in a dose-dependent manner and decreased histological signs of acute inflammation in the treated animals. In addition, quercetin treatment suppressed leucocyte recruitment, decreased chemokine levels, decreased levels of the lipid peroxidation end-product malondialdehyde, and increased antioxidant enzyme activity in treated rats., Conclusions: These results indicated that quercetin exerted a strong anti-inflammatory effect that may be useful for the treatment of acute gouty arthritis., (© 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.)

Objectives: Extracorporeal circulation is associated with ischaemia-reperfusion-induced oxidative stress and atrial fibrillation (AF). Ageing is the major risk factor for this arrhythmia. Reinforcing the antioxidant defence system would be expected to protect the myocardium against ischaemia-reperfusion damage. We studied the effect of antioxidant reinforcement and ageing on the occurrence of postoperative AF., Methods: A randomized, double-blind, placebo-controlled trial was performed in patients scheduled for cardiac surgery with extracorporeal circulation. Supplementation with omega-3 polyunsaturated fatty acid (PUFA) and vitamins C and E, or placebo was administered to 152 patients divided by age: young patients (30-59 years) and old patients (60-80 years). For the detection of AF, we used 12-lead and Holter EKGs. Antioxidant enzyme activity was determined in atrial tissue. Oxidative stress was assessed through plasma malondialdehyde levels., Results: Supplemented patients over 60 years old showed higher glutathione peroxidase activity than control patients in the same age range. There was no difference between the supplemented and placebo groups in patients under 60 years old. The decrease in the incidence of postoperative AF in supplemented patients was more marked in the older patients than in the younger ones., Conclusions: Since the antioxidant supplementation with n-3 PUFAs and vitamins C and E resulted in a more marked reduction of postoperative AF in older patients, it could be suggested that the efficacy of this therapy improves with ageing.

Fifty cases of severe malaria were studied for their oxidant and antioxidant status. Severe anemia (54%) was the most common presentation followed by hyperpyrexia, cerebral malaria and jaundice. Plasma malondialdehyde, protein carbonyl, nitrite, ascorbic acid and copper levels were significantly raised in cases as compared with controls (p < 0.001). Plasma ceruloplasmin, glutathione and superoxide dismutase levels were significantly decreased in children with severe malaria (p < 0.001). Plasma zinc was increased in cases but difference is not statistically significant. Significantly decreased level of nitrites and increased value of glutathione was found in patients with hemoglobinuria and jaundice, respectively. The significantly elevated malondialdehyde and protein carbonyl levels reflect the increased oxidative stress, whereas decreased levels of glutathione and superoxide dismutase point toward utilization of the antioxidants in severe malaria. Thus, changes in oxidants and antioxidants observed suggest the production of reactive oxygen species and their possible role in pathogenesis of severe malaria.

Background: Accelerated atherosclerosis is the major cause of mortality in patients on chronic haemodialysis (HD). The aim of this study was to evaluate the relationship between oxidative DNA damage [8-hydroxy-2'-deoxyguanosine/deoxyguanosine ratio (8-OHdG/dG ratio)], oxidative stress biomarkers and endothelial function in HD patients as an indicator of atherosclerosis., Methods: Forty-four chronic HD patients without known atherosclerotic disease and 55 age- and sex-matched healthy individuals were included in the study. Plasma malondialdehyde (MDA) levels and 8-OHdG/dG ratio were determined as oxidative stress markers. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured as antioxidants. Endothelial function was assessed by ultrasonography., Results: 8-OHdG/dG ratio and MDA levels were higher in HD patients than controls while SOD and GPx activities were lower in HD patients compared to controls. Flow-mediated dilatation FMD% in HD patients were lower than the control group (7.28 ± 0.79 versus 11.18 ± 0.82, P < 0.001). There was a significant negative correlation between FMD% and 8-OHdG/dG ratio (r = -0.678, P < 0.01) and MDA levels (r = -0.517, P < 0.01), while there was a significant positive correlation between FMD% and SOD (r = 0.538, P < 0.01) and GPx levels (r = 0.720, P < 0.01)., Conclusions: Our data have demonstrated that HD patients exhibit increased oxidative DNA damage and decreased antioxidant activity. We propose that endothelial function is negatively correlated with 8-OHdG/dG ratio and positively correlated with antioxidant enzymes. To our knowledge, this is the first study to demonstrate the inverse relationship between endothelial function and plasma oxidative DNA damage in HD patients.

Objective: This study was conducted to assess the effects of chronic daily methylsulfonylmethane (MSM) supplementation on known markers of oxidative stress following acute bouts of exercise in untrained healthy young men., Methods: Eighteen untrained men volunteered for this study. Participants were randomized in a double-blind placebo-controlled fashion into two groups: MSM (n = 9) and placebo (n = 9). The participants took supplementation or placebo daily for 10 days before running. Participants ran 14 km. The MSM supplementation was prepared in water at 50 mg/kg body weight. The placebo group received water. Serum malondialdehyde (MDA), protein carbonyl (PC) and plasma oxidized glutathione (GSSG) were measured as markers of oxidative stress. The plasma-reduced glutathione (GSH) level and the GSH/GSSG ratio were determined as markers of plasma antioxidant capacity., Key Findings: Acute exercise led to elevated levels of serum MDA, PC and plasma GSSG. MSM supplementation maintained PC, MDA and GSSG at lower levels after exercise than the placebo. The plasma level of GSH and the ratio of GSH/GSSG were significantly higher in the MSM supplemented group., Conclusions: These results suggest that chronic daily oral supplementation of MSM has alleviating effects on known markers of oxidative stress following acute bouts of exercise in healthy young men., (© 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.)

Aims: Interleukin (IL)-15 is highly expressed in skeletal muscle, where it exerts anabolic effects, increasing protein content in muscle fibres and promoting muscle growth. Alcoholics frequently suffer myopathy. Therefore, we analyse the behaviour of IL-15 (and other myokines, such as IL-6, IL-8 and tumour necrosis factor α (TNF-α)) in alcoholics., Methods: These myokines and also malondialdehyde (MDA)--a lipid peroxidation product--were determined by radioimmunoanalytic techniques in blood samples of 35 chronic alcoholics and 13 age- and sex-matched controls, and compared with body composition, nutritional status, liver function, amount of ethanol and routine biochemical variables., Results: IL-15, IL-6, TNF-α, IL-8 and MDA were all higher in alcoholics than in controls; MDA and IL-6 were clearly related with liver function impairment and short-term prognosis, whereas IL-15 was higher among those who died and was related to serum bilirubin. No relation was found between IL-15 and lean mass., Conclusion: IL-15 levels were higher in alcoholics than in controls, especially among those who died within 18 months after admission. They are not related with muscle mass, intensity of alcoholism or nutritional status, but only with serum bilirubin. IL-6 showed inverse correlations with liver function, intensity of alcoholism, nutritional status, left arm muscle mass and short-term mortality.

Objective: The present study was designed to observe the effects of 3,6'-disinapoyl sucrose (DISS), an active oligosaccharide ester component obtained from the roots of Polygala tenuifolia Willd., on behavioral and biochemical aspects of depression induced by chronic mild stress (CMS) in rats. It is the first exploration of the possible association between DISS's antidepressant-like effects and biochemical markers of depression, and involved measuring monoamine oxidase (MAO) activity, cortisol levels, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels., Methods: Rats were exposed to stressor once daily for consecutive 5 weeks. DISS and a positive control drug, fluoxetine, were administered via gastric intubation to once daily for consecutive 3 weeks from the third week., Key Findings: The results showed that rats subjected to CMS exhibit a reduction in sucrose intake. Conversely, brain MAO-A and MAO-B activity, plasma cortisol levels, and MDA levels were increased, while SOD activity was decreased following CMS exposures. DISS significantly inhibited MAO-A and MAO-B activity and blocked plasma elevated cortisol level, an indicator of the hypothalamic-pituitary-adrenal (HPA) axis. In addition, DISS increases SOD activity, inhibits lipid peroxidation, and lessens production of MDA., Conclusion: These results suggest that DISS may possess potent and rapid antidepressant properties, which are mediated via MAO, the HPA axis and oxidative systems. These antidepressant actions make DISS a potentially valuable drug for the treatment of depression., (© 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.)

Objectives: The hepatoprotective activity and molecular mechanism of betulinic acid (BA) was investigated on acute liver failure induced by d-galactosamine (D-GalN)/lipopolysaccharide (LPS) in vivo., Methods: Mice were administered with different doses of BA (20 mg/kg or 50 mg/kg, i.p.) 1 h before injection of D-GalN (700 mg/kg)/LPS (10 µg/kg) and sacrificed 6 h after treatment with D-GalN/LPS., Key Findings: Pretreatment with BA significantly prevented the increases of serum aspartate aminotransferase and alanine aminotransferase, while it increased the content of glutathione and catalase, and reduced malondialdehyde. BA showed obvious anti-oxidant effects and prevented D-GalN/LPS-induced apoptosis, as indicated by DNA ladder. BA treatment resulted in regulation of the mitogen-activated protein kinase. We found that BA mediated production of c-jun NH(2) -terminal protein kinase and extracellular signal-regulated kinase induced by D-GalN/LPS, promoted the expression of B-cell CLL/lymphoma 2 (Bcl-2) and restored mitochondrial outer membrane permeabilization., Conclusions: The results suggested that BA prevented D-GalN/LPS-induced acute liver failure by upregulation of Bcl-2 and antioxidation and mediation of cytokines causing apoptotic cell death and lessened liver damage., (© 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.)

Objectives: Glycyrrhizin is the main water-soluble constituent of the root of liquorice (Glycyrrhiza glabra). The study investigates the effect of glycyrrhizin on streptozotocin (STZ)-induced diabetic changes and associated oxidative stress, including haemoglobin-induced free iron-mediated oxidative reactions., Methods: Male Wistar rats were grouped as normal control, STZ-induced diabetic control, normal treated with glycyrrhizin, diabetic treated with glycyrrhizin and diabetic treated with a standard anti-hyperglycaemic drug, glibenclamide. Different parameters were studied in blood and tissue samples of the rats., Key Findings: Glycyrrhizin treatment improved significantly the diabetogenic effects of STZ, namely enhanced blood glucose level, glucose intolerant behaviour, decreased serum insulin level including pancreatic islet cell numbers, increased glycohaemoglobin level and enhanced levels of cholesterol and triglyceride. The treatment significantly reduced diabetes-induced abnormalities of pancreas and kidney tissues. Oxidative stress parameters, namely, serum superoxide dismutase, catalase, malondialdehyde and fructosamine in diabetic rats were reverted to respective normal values after glycyrrhizin administration. Free iron in haemoglobin, iron-mediated free radical reactions and carbonyl formation in haemoglobin were pronounced in diabetes, and were counteracted by glycyrrhizin. Effects of glycyrrhizin and glibenclamide treatments appeared comparable., Conclusion: Glycyrrhizin is quite effective against hyperglycaemia, hyperlipidaemia and associated oxidative stress, and may be a potential therapeutic agent for diabetes treatment., (© 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.)

Fucoidan, a sulfated polysaccharide extracted from various types of brown seaweed, possesses a wide range of pharmacological properties. We investigated the protective effect of fucoidan on dimethylnitrosamine-induced liver fibrogenesis in rats and its mechanism. Liver fibrosis was induced by injecting DMN (10 mg/kg, 3 times per week, I.P.) for 4 weeks, and fucoidan was simultaneously administered (100 mg/kg, 3 times per week, P.O.). The anti-oxidative and anti-inflammatory effects of fucoidan were observed by relative mediators. Fucoidan improved liver fibrosis by inhibiting the expression of transforming growth factor beta 1 (TGF-β(1))/Smad3 and the tissue inhibitor of metalloproteinase 1 (TIMP-1), and increasing the expression of metalloproteinase-9 (MMP-9). Fucoidan also significantly decreased the accumulation of the extracellular matrix (ECM) and collagen. These results suggest that fucoidan had an anti-fibrotic effect, which was exerted by inhibiting the TGF-β/Smad pathway, as well as anti-oxidative and anti-inflammatory effects.

Background: Podoconiosis (endemic nonfilarial elephantiasis) occurs in susceptible individuals who go barefoot in regions of irritant volcanic soil. Silicate particles absorbed via the skin are thought to induce an inflammatory process and a consequent endolymphangitis of the lower leg lymphatics., Objectives: To establish which oxidative stress biomarkers play a part in the inflammatory process, and to test whether transforming growth factor (TGF)-beta1 also has a pathogenetic role., Patients and Methods: We enrolled 50 patients with early clinical stage disease, 43 patients with advanced stage disease and 35 local healthy controls. Oxidative stress biomarkers included serum total peroxides (TP), total antioxidant capacity (TAC), total nitrate plus nitrite (TN), malondialdehyde (MDA) and total superoxide dismutase (SOD) activity. The oxidative stress index (OSI) was also determined. Serum total TGF-beta1 was assayed using sandwich enzyme-linked immunosorbent assay., Results: Compared with healthy controls, patients with early stage disease showed significantly higher mean levels of TP (P < 0.001), MDA (P < 0.05) and OSI (P < 0.01); and significantly lower mean concentrations of SOD (P < 0.001) and TGF-beta1 (P < 0.001). Mean levels of TGF-beta1 were even lower among patients with advanced stage disease (P < 0.001). Mean TAC levels were significantly lower among patients with advanced disease than either other group (P < 0.001)., Conclusions: This is the first study, to our knowledge, to attempt to elucidate the molecular pathogenetic events in podoconiosis. We conclude that TGF-beta1 may have a pathogenetic role, with oxidative stress playing a minor role in the early stages of disease.

Objectives: The protective effect of CDP-choline in spinal cord transection and the mediation of its cardiovascular effects were investigated., Methods: Spinal cords of rats were transected at the T1-T2 levels. CDP-choline (250 mg/kg; intravenous) was administered 2 h and/or 24 h after the injury., Key Findings: Spinal cord transection caused severe tissue damage, decreased mean arterial pressure, heart rate, plasma adrenaline, and noradrenaline but increased plasma vasopressin levels. Repeated CDP-choline treatment attenuated the degree of tissue injury. Administration of CDP-choline at 2 h after transection transiently increased blood pressure and decreased heart rate, while it produced a small decrease in blood pressure and heart rate when it was given at 24 h. Plasma adrenaline levels were higher in the group where CDP-choline was given repeatedly. Plasma noradrenaline and vasopressin levels did not change additionally after CDP-choline injections in all groups. In order to determine if CDP-choline attenuates the oxidative injury induced by transection, we measured blood superoxide dismutase, glutathione peroxidase activity and malondialdehyde levels. Repeated CDP-choline administration decreased blood superoxide dismutase and glutathione peroxidase activity without any effect on malondialdehyde levels., Conclusions: Data indicate that repeated intravenous CDP-choline treatment prevents tissue damage in spinal shock conditions in the acute phase. The cardiovascular effects of the drug do not seem to be responsible for this protection but the drug-induced attenuation of the oxidative stress may play a role.

Ankylosing spondylitis (AS) is a chronic inflammatory disease mainly affecting the spine and sacroiliac joints. Mediators such as macrophage migration inhibitory factor (MIF) and interleukin-10 (IL-10) are thought to be involved in several inflammatory conditions, including AS. Proinflammatory cytokines regulate the production of oxidative stress markers, such as nitric oxide (NO) and malondialdehyde (MDA). Although oxidative stress and lipid peroxidation have been reported in AS, the association of AS with commonly known oxidative stress markers and cytokines remains uncertain. We have therefore studied whether serum MIF levels are elevated in patients with AS and whether the levels correlate with oxidative stress markers and disease activity parameters. Twenty-five AS patients and 18 healthy controls participated in this study; subjects with hypertension, diabetes, hyperlipidemia, and obesity were excluded. The levels of acute phase reactants, serum levels of glucose, lipids, MIF, IL-10, NO and MDA were studied. Spinal mobility was assessed by the Bath Ankylosing Spondylitis Metrology Index (BASMI). Patients were also assessed using with the Bath Ankylosing Spondylitis Functional Index and the Bath Ankylosing Spondylitis Disease Activity Index. Age and sex distribution were found to be comparable between AS patients and controls (p > 0.05). Acute phase reactants and MIF levels were significantly higher (p < 0.05) and IL-10 levels were significantly lower (<0.001) in the AS patients than in controls. There was a significant correlation between BASMI and MIF levels in AS patients (r = 0.714, p < 0.001). Based on these results, MIF may be involved in the pathogenesis of the chronic inflammation in AS and, consequently, targeting MIF may be beneficial in preventing complications or in initiating early treatment of the disease.

The aim of the study was to analyze the oxidative stress response after severe burn injury. We studied the effect of two methods of fluid resuscitation regimes on the oxidative stress reaction. Sixteen patients were involved in the study. Inclusion criteria were the presence of flame burn injury affecting >20% of BSA and in-hospital fluid resuscitation started within 3 hours after injury. Patients were randomly assigned into two groups. In the first group (n=8), the fluid resuscitation was guided by the hourly urine output and in the second (n=8), by the intrathoracic blood volume index. Blood sample was taken from the patients at admission and on the following five mornings. White blood cell count normalized by the third day in both groups, but the relative number of granulocytes and lymphocytes significantly (P<.05) diverged between hourly urine output and intrathoracic blood volume index groups from the fourth day of trauma. Plasma malondialdehyde level (P<.05 vs control population), reactive oxygen species production in whole blood (P<.05 vs control population), and catalase activity were elevated, whereas glutathione, plasma sulfhydryl groups level (P<.05 vs control population), and superoxide dismutase enzyme activity lowered in both groups. Our results confirmed that burn injury induces pronounced oxidative stress. The main finding is that fluid resuscitation regimes have different impact on prooxidant status, mainly on the granulocyte function but not on the changes in endogenous antioxidants in burned patients.

Objectives: Revascularization therapy is the mainstay of treatment in the management of myocardial infarction in normal and diabetic patients. We attempted to evaluate the cardioprotective actions of quercetin and rutin in ischaemia-reperfusion-induced myocardial infarction in both normal and diabetic rats., Methods: Myocardial infarct size was measured using the staining agent 2,3,5-triphenyltetrazoliumchloride. Serum and tissue malondialdehyde levels and superoxide dismutase and catalase in heart tissue were estimated spectrophotometrically. A lead II electrocardiogram was monitored at various intervals throughout the experiment., Key Findings: Results demonstrated the larger infarct size, enhanced lipid peroxidation, partial depletion of antioxidant enzymes and drastic drop in heart rate in diabetic hearts subjected to in-vivo ischaemia-reperfusion in comparison to normal rats subjected to ischaemia-reperfusion. Furthermore, quercetin and rutin significantly limit the infarct size in both normal and diabetic animals in a similar fashion. However, rutin offered complete cardioprotection at a dose of 10 mg/kg in terms of limiting infarct size. Both flavonoids could partially but significantly attenuate the lipid peroxidation. In addition, treatment has shown moderate improvement in heart rate in both normal and diabetic rats., Conclusions: Our data suggest the possible cardioprotective effects of quercetin and rutin in ischaemia-reperfusion injury in both normal and diabetic rats, and that protection might be in part due to the attenuation of oxidative stress and moderate increment in antioxidant reserves.

Background: Available data about oxidative status in patients with end-stage renal disease (ESRD) or on dialysis are contradictory. The present cross-sectional study aimed to investigate the role of renal insufficiency and dialysis on lipid peroxidation. To separate the effects of uraemia from dialysis-induced stress, we enrolled 26 patients with renal insufficiency on conservative treatment (ESRD), 23 on peritoneal dialysis (PD), 30 on haemodialysis (HD) and 30 controls., Methods: Plasma malondialdehyde (MDA) levels, both total (tMDA) and free (fMDA), were measured as indexes of oxidative stress by gas chromatography-mass spectrometry. Bound MDA (bMDA) levels were calculated as the difference between tMDA and fMDA., Results: Total and bMDA concentrations were significantly higher in patients than in controls (ESRD > HD > PD). In PD and HD patients, fMDA levels were similar and significantly higher than in ESRD. Multivariate analysis, with tMDA, fMDA and bMDA as dependent variables, showed similar and significant tMDA and bMDA relations with residual renal function (t = -2.160, P = 0.035) and albumin (t = -2.049, P = 0.045). Erythropoietin dose affected only fMDA values (t = -2.178, P = 0.034)., Conclusions: Free and bMDA concentrations identified different MDA patterns. Bound MDA, not excreted by kidneys, accounts alone for high tMDA concentrations in ESRD patients, while both fMDA and bMDA contribute to tMDA values in dialysis patients. These findings show that increased tMDA could be indicative not only of recent lipid peroxidation, and they also highlight the importance of evaluating free, bound and total MDA in patients with reduced renal function in order to assess their oxidative status.

Design: In order to characterize whether different degrees of adipose tissue storage may be associated with markers of early atherosclerosis, we evaluated oxidant-antioxidant status and inflammatory markers and determined carotid intima-media thickness (cIMT) in healthy constitutional lean and obese pre-pubertal children., Methods: Eighty healthy pre-pubertal lean and obese children were recruited and compared with 40 age, gender, and pubertal stage-matched normal controls. Anthropometric measurements, oxidant (urinary isoprostanes (PGF-2alpha), lag phase, and malondialdehyde (MDA)) and antioxidant status (vitamin E), inflammatory markers (high sensitive C-reactive protein (hs-CRP)), and insulin sensitivity (fasting glucose-insulin ratio, homeostasis model assessment of insulin resistance (HOMA-IR)) were investigated. Furthermore, cIMT was measured by high-resolution ultrasound., Results: hs-CRP was not different between lean and control subjects (P=0.45), while higher values were found in obese compared with lean and control children (P<0.001 and P<0.001 respectively). PGF-2alpha and MDA were higher while lag phase shorter in lean and obese subjects compared with controls (lean P<0.001; P<0.001; P<0.001 and obese P<0.001; P<0.001; P<0.001 respectively), while no differences were documented between lean and obese subjects (P=0.78, P=0.019, and P=0.53 respectively). Compared with controls, cIMT was increased in lean and in obese subjects (P=0.001; P=0.004), while no differences were documented between obese and lean subjects (P=0.1). In a multiple stepwise linear regression analysis, cIMT was related with PGF-2alpha (beta=0.641, P<0.001) and HOMA-IR (beta=0.307; P<0.001)., Conclusions: Pre-pubertal lean and obese children present increased oxidative stress and impaired inflammation and insulin sensitivity, which in turn seem to result in similar impaired endothelial dysfunction and early signs of atherosclerosis, already in childhood.

The protective effect of selenoarginine against oxidation resistance was investigated in D-galactose (D-gal)-induced aging mice. The mice were divided into four groups (n=15): a normal group, a model group, a lowdose selenoarginine group (8.35 microg of Se/kg b.w./d), and a high dose selenoarginine group (16.78 microg of Se/kg b.w./d). The aging model was induced by s.c. injection D-galactose dissolved in 0.9% normal saline of a dose of 150 mg/kg/d for 6 weeks. The mice in the normal group received s.c. injection of sterile normal saline at the same dose and frequency. The results showed that oxidative stress in the liver, kidney, and brain tissues and the serum of the mice was induced by D-galactose, but selenoarginine had an obviously protective effect against D-galactose-induced aging mice. Lowdose selenoarginine performed better than high dose selenoarginine. The protective effect of selenoarginine on D-galactose-induced aging mice can be attributed to elevation of the activity of antioxidase and enhanced antioxidant defenses.

Background: Residual renal function (RRF) correlates with survival in peritoneal dialysis (PD). We investigated the association between oxidative stress and RRF in PD., Methods: Adequacy of dialysis, total and free malondialdehydes (MDA), and lipid hydroperoxides (LHP) were obtained from 23 stable PD patients., Results: Free MDA level decreased with total weekly Kt/V urea (r = -0.51, P = 0.013) and urinary Kt/V (KRU) (r = -0.53, P = 0.009), but not with peritoneal Kt/V. Similar results were found with LHP level. In multivariate analysis, total weekly Kt/V urea and KRU remained associated with free MDA and LHP, independently of gender, nutritional or inflammatory status, and peritoneal permeability., Conclusion: A preserved RRF is associated with lower serum levels of lipid peroxidation products among PD patients.

Objectives: Various experimental observations show that morphine treatment generates reactive oxygen species, and that its discontinuation leads to signs of withdrawal. We therefore investigated plasma malondialdehyde and vitamin E levels under both conditions to verify the occurrence of any alterations in oxidative metabolism, and whether these are associated with behavioural changes., Methods: We investigated the effects of morphine or morphine plus naloxone on plasma malondialdehyde, vitamin E levels and withdrawal signs such as jumping, wet dog shakes and faecal excretion in rats. Furthermore, isopropylnoradrenaline was injected in rabbits to verify its effects on plasma malondialdehyde levels., Key Findings: Morphine treatment increased free malondialdehyde and decreased vitamin E levels. The elevation in malondialdehyde levels were exacerbated by the abrupt removal of morphine by naloxone, which also led to the appearance of withdrawal signs. The increased malondialdehyde values can be attributed to the interactions of reactive oxygen species with unsaturated fatty acids, and the lowered levels of vitamin E to its interactions with reactive oxygen species., Conclusions: A connection seems to exist between altered peroxide status and withdrawal signs in abstinent animals.

Objectives: Hydrogen sulfide (H2S) is an endogenously gaseous mediator, regulating many pathophysiological functions in mammalian cells. H2S has been shown to inhibit myocardial ischaemia-reperfusion (I/R) injury. However, little is known about whether H2S could modulate intestinal I/R injury. This study aimed to investigate the effect of H2S on intestinal I/R injury and potential mechanism(s) underlying the action of H2S in regulating the development of intestinal I/R injury in rats., Methods: Following surgical induction of intestinal I/R injury for 1 h, groups of Sprague-Dawley rats were treated with, or without, tetramethylpyrazine (8 mg/kg), or sodium hydrosulfide (NaHS, an H2S donor at 7 or 14 micromol/kg) 30 min after occlusion. All rats were sacrificed immediately after the reperfusion. Their intestinal injury, together with that of sham-control rats, was histologically examined and their sera and intestinal malondialdehyde (MDA), superoxide dismutase (SOD), peroxidase (GSH-Px) activities were characterized by biochemical analysis., Key Findings: The results showed that NaHS significantly reduced intestinal I/R injury and the levels of sera and intestinal MDA activity, and dramatically increased the levels of serum and intestinal SOD and GSH-Px activity., Conclusions: The results suggest that H2S protects from intestinal I/R injury in rats, which is associated with increase in the activity of antioxidant enzymes.

Background: Altered renal vasodilatation and oxidative stress are important mechanisms of contrast-induced nephropathy (CIN). The aim of the present study was to assess the effect of nebivolol, a beta blocker, on prevention of CIN. We hypothesized that nebivolol may prevent CIN due to its renal vasodilatation and antioxidant effects., Methods: Thirty-two Wistar-albino rats were divided into four groups (n = 8 each): control (C), contrast media (CM), nebivolol (N), and nebivolol + contrast media (NCM). CIN was induced by administration of intravenous high-osmolar contrast media diatrizoate (6 ml/kg) after 72 h of dehydration. Nebivolol (2 mg/kg) was given internally once daily for 5 days. Kidney function parameters, nitric oxide metabolites and oxidative stress markers were measured. Kidneys were excised for pathological evaluation., Results: The decrease of creatinine clearance was 0.180 +/- 0.11 mg/dl in CM, and 0.030 +/- 0.10 mg/dl in NCM (P = 0.01). Microproteinuria was ameliorated using nebivolol (P = 0.001). Serum protein carbonyl content, malonyldialdehyde and kidney thiobarbituric acid-reacting substances levels were higher in CM than in C (P = 0.003, P < 0.001 and P = 0.034, respectively) and serum thiol was lower in CM than in C (P = 0.001). However, oxidative stress markers were similar in NCM and C. Diatrizoate decreased kidney nitrite levels, but nebivolol increased them (P = 0.027). Nebivolol attenuated the tubular necrosis, proteinaceous casts and medullary congestion, although significant protective effects, were observed in tubular necrosis (P = 0.001) and proteinaceous cast (P < 0.001)., Conclusion: This study demonstrated the protective role of nebivolol against CIN.