In Vitro Inhibition of Xanthine Oxidase Purified from Arthritis Serum Patients by Nanocurcumin and Artemisinin Active Compounds.

Curcumin and artemisinin are commonly used in traditional East Asian medicine. In this study, we investigated the inhibitory effects of these active compounds on xanthine oxidase (XO) using allopurinol as a control. XO was purified from the serum of arthritis patients through ammonium sulfate precipitation (65%) and ion exchange chromatography on diethylaminoethyl (DEAE)-cellulose. The specific activity of the purified enzyme was 32.5 U/mg protein, resulting in a 7-fold purification with a yield of 66.8%. Molecular docking analysis revealed that curcumin had the strongest interaction energy with XO, with a binding energy of -9.28 kcal/mol. The amino acid residues Thr1077, Gln762, Phe914, Ala1078, Val1011, Glu1194, and Ala1079 were located closer to the binding site of curcumin than artemisinin, which had a binding energy of -7.2 kcal/mol. In vitro inhibition assays were performed using nanocurcumin and artemisinin at concentrations of 5, 10, 15, 20, and 25 µg/mL. Curcumin inhibited enzyme activity by 67-91%, while artemisinin had a lower inhibition ratio, which ranged from 40-70% compared to allopurinol as a control.

Ameliorative effect and mechanism of Yi-Suan-Cha against hyperuricemia in rats.

BACKGROUND: This study aimed to evaluate the urate-lowering effects of Yi-Suan-Cha and explore its underlying mechanisms in experimental hyperuricemia induced in rats. METHODS: Forty-eight male SD rats were randomly allocated into normal control, model, allopurinol, benzbromarone, low-dose Yi-Suan-Cha (0.2 g/ml), and high-dose Yi-Suan-Cha (0.4 g/ml) groups (n = 8 rats per group). Rat models of hyperuricemia were established through intragastric administration of adenine 25 mg/kg + potassium oxalate 300 mg/kg for 3 weeks. After the last administration, serum uric acid, creatinine, and urea nitrogen levels were measured. Renal histopathology was observed by hematoxylin-eosin staining. Xanthine oxidase level in serum and liver homogenates was measured by ELISA. The protein and mRNA expression of URAT1, ABCG2, OAT1, and GLUT9 in the kidney was detected by Western blotting and RT-PCR, respectively. RESULTS: The serum uric acid levels were significantly lowered in all medication groups than in the model group. The benzbromarone and both Yi-Suan-Cha groups showed clear kidney structures with no obvious abnormalities. Compared with the normal control group, the model group showed increased URAT1/GLUT9 protein expression and decreased ABCG2/OAT1 protein expression. Compared with the model group, both Yi-Suan-Cha groups showed decreased URAT1/GLUT9 protein expression and increased ABCG2/OAT1 protein expression. Compared with that in the normal control group, URAT1/GLUT9 mRNA expression increased in the model group. Compared with the model group, the low-dose and high-dose Yi-Suan-Cha groups showed decreased URAT1/GLUT9 mRNA expression and increased ABCG2/OAT1 mRNA expression. CONCLUSION: Yi-Suan-Cha may lower uric acid level by downregulating URAT1/GLUT9 expression and upregulating ABCG2/OAT1 expression.

In Vitro Interaction of 5-Aminoorotic Acid and Its Gallium(III) Complex with Superoxide Radical, Generated by Two Model Systems.

Increased levels of the superoxide radical are associated with oxidative damage to healthy tissues and with elimination of malignant cells in a living body. It is desirable that a chemotherapeutic combines pro-oxidant behavior around and inside tumors with antioxidant action near healthy cells. A complex consisting of a pro-oxidant cation and antioxidant ligands could be a potential anticancer agent. Ga(III) salts are known anticancer substances, and 5-aminoorotic acid (HAOA) is a ligand with antioxidant properties. The in vitro effects of HAOA and its complex with Ga(III) (gallium(III) 5-aminoorotate (GaAOA)) on the in vitro accumulation of superoxide and other free radicals were estimated. Model systems such as potassium superoxide (KO2), xanthine/xanthine oxidase (X/XO), and rat blood serum were utilized. Data suggested better antioxidant effect of GaAOA compared to HAOA. Evidently, all three ligands of GaAOA participated in the scavenging of superoxide. The effects in rat blood serum were more nuanced, considering the chemical and biochemical complexity of this model system. It was observed that the free-radical-scavenging action of both compounds investigated may be manifested via both hydrogen donation and electron transfer pathways. It was proposed that the radical-scavenging activities (RSAs) of HAOA and its complex with Ga(III) may be due to a complex process, depending on the concentration, and on the environment, nature, and size of the free radical. The electron transfer pathway was considered as more probable in comparison to hydrogen donation in the scavenging of superoxide by 5-aminoorotic acid and its gallium(III) complex.

A Lanosteryl Triterpene (RA-3) Exhibits Antihyperuricemic and Nephroprotective Effects in Rats.

Considering the global health threat posed by kidney disease burden, a search for new nephroprotective drugs from our local flora could prove a powerful strategy to respond to this health threat. In this study we investigated the antihyperuricemic and nephroprotective potential of RA-3, a plant-derived lanosteryl triterpene. The antihyperuricemic and nephroprotective effect of RA-3 was investigated using the adenine and gentamicin induced hyperuricemic and nephrotoxicity rat model. Following the induction of hyperuricemia and nephrotoxicity, the experimental model rats (Sprague Dawley) were orally administered with RA-3 at 50 and 100 mg/kg body weight, respectively, daily for 14 days. Treatment of the experimental rats with RA-3, especially at 100 mg/kg, effectively lowered the serum renal dysfunction (blood urea nitrogen and creatinine) and hyperuricemic (uric acid and xanthine oxidase) biomarkers. These were accompanied by increased antioxidant status with decrease in malondialdehyde content. A much improved histomorphological structure of the kidney tissues was also observed in the triterpene treated groups when compared to the model control group. It is evident that RA-3 possesses the antihyperuricemic and nephroprotective properties, which could be vital for prevention and amelioration of kidney disease.

Lycium barbarum polysaccharides protect mice from hyperuricaemia through promoting kidney excretion of uric acid and inhibiting liver xanthine oxidase.

CONTEXT: Lycium barbarum L. (Solanaceae) polysaccharides (LBPs) are important active constituents that have demonstrated kidney protection. OBJECTIVE: This study investigated the effect of LBPs on hyperuricaemia and explored the underlying mechanism in mice. MATERIALS AND METHODS: Thirty-six C57BL/6 mice were randomly divided into the control group, hyperuricaemia group, allopurinol group (5 mg/kg) and three LBP groups (n = 6). The LBP groups were treated orally with LBPs at 50, 100 and 200 mg/kg body weight for 7 days. We examined the levels of serum uric acid (SUA) and urinary uric acid (UUA), as well as xanthine oxidase (XOD) activities. mRNA and protein were quantified by quantitative real-time PCR and Western blotting, respectively. RESULTS: LBPs treatment (100 and 200 mg/kg) significantly reduced the SUA levels to 4.83 and 4.48 mg/dL, and markedly elevated the UUA levels to 4.68 and 5.18 mg/dL (p < 0.05), respectively, while significantly increased the mRNA and protein expression levels of renal organic anti-transporter 1 (OAT1) and organic anti-transporter 3 (OAT3), and markedly decreased the levels of glucose transporter 9 (GLUT9) (p < 0.05). Additionally, the serum XOD activities were reduced to 31.5 and 31.1 mU/mL, and the liver XOD activities were reduced to 80.6 and 75.6 mU/mL after treatment with 100 and 200 mg/kg LBPs (p < 0.01), respectively. DISCUSSION AND CONCLUSIONS: This study demonstrated the potential role of LBPs in reducing the uric acid level in hyperuricemic mice. A border study population should be evaluated. These results are valuable for the development of new anti-hyperuricaemia agents from LBPs.

Do CO2 and oxidative stress induce cancer?: a brief study about the evaluation of PON 1, CAT, CA and XO enzyme levels on head and neck cancer patients.

Head and neck cancer (HNC) is one of the most common malignancies in the world. HNC is a group of cancers that starts in the mouth, nose, throat, larynx, sinuses, or salivary glands. According to this section of the body parts; induction of cancer can be associated with CO2 and oxidative stress. The aim of this study is to assess the activities of carbonic anhydrase (CA), catalase (CAT), paraoxonase1 (PON1), and xanthine oxidase (XO) activities in 89 HNC patients and 115 healthy volunteers. Paraoxonase1 activity was found lower in HNC cancer patients. There is no statistically significant difference between patients and controls for catalase, carbonic anhydrase, and xanthine oxidase enzyme levels. According to this results, paraoxonase1 levels could be a candidate as an oxidative marker in HNC patients, but further studies are needed to investigate the other type of cancer related PON1 and the other enzyme levels.

Effects of ChondroT on potassium Oxonate-induced Hyperuricemic mice: downregulation of xanthine oxidase and urate transporter 1.

BACKGROUND: ChondroT, a new herbal medication, consists of the water extracts of Osterici Radix, Lonicerae Folium, Angelicae Gigantis Radix, Clematidis Radix, and Phellodendri Cortex (6:4:4:4:3). We previously reported that ChondroT showed significant anti-arthritis and anti-inflammatory effects. METHODS: This study was designed to evaluate the effect of ChondroT on hyperuricemia. First, the effect of ChondroT was evaluated on xanthine oxidase (XOD) activity in vitro. The anti-hyperuricemic effect of ChondroT was also studied in potassium oxonate (PO)-induced hyperuricemic model mice. Uric acid (UA) and XOD were evaluated in the serum, urine, and liver of the mice. In addition, we measured serum creatinine (Cr) and blood urea nitrogen (BUN) levels as well as mRNA expression of the mouse urate transporter 1 (mURAT1) to evaluate kidney function and urate excretion in hyperuricemic mice. RESULTS: ChondroT showed in vitro XOD inhibitory activity in a dose-dependent manner (P < 0.05). We demonstrated that ChondroT (37.5, 75 and 150 mg/kg) significantly reduced serum UA (P < 0.01 and P < 0.001, respectively), and upregulated urinary UA (P < 0.001, respectively) in PO-induced hyperuricemic mice. In addition, ChondroT (75 and 150 mg/kg) significantly reduced Cr (P < 0.05 and P < 0.01, respectively), BUN (P < 0.05 and P < 0.001, respectively), GOT (P < 0.05 and P < 0.01, respectively), and GPT (P > 0.05 and P < 0.05, respectively) levels in PO-induced hyperuricemic mice. ChondroT (75 and 150 mg/kg) also significantly downregulated serum (P < 0.05) and liver (P < 0.05) XOD activity. Compared to the hyperuricemic mice, the ChondroT (37.5, 75, and 150 mg/kg)-treated mice showed decreased mURAT1 protein expression level. CONCLUSION: ChondroT displayed anti-hyperuricemic effects by regulating XOD activity and kidney mURAT1.

Serum adenosine deaminase and xanthine oxidase activities in silver catfish naturally infected with Ichthyophthirius multifiliis: The influence of these enzymes on inflammatory and oxidative status.

Adenosine deaminase (ADA) activity, through adenosine (Ado) levels, as well as xanthine oxidase (XO) activity through uric acid levels exerts an essential role on immune and inflammatory responses during infectious diseases. Thus, the aim of this study was to evaluate the involvement of seric ADA and XO activities in the inflammatory and oxidative status of silver catfish naturally infected with Ichthyophthirius multifiliis. Seric ADA activity decreased, while Ado levels increased in infected animals compared to uninfected animals. Moreover, the seric XO activity increased in infected animals compared to uninfected animals, alongside the seric levels of uric acid, metabolites of nitric oxide (NOx) and reactive oxygen species (ROS). Based on this evidence, the downregulation of seric ADA activity exerts an anti-inflammatory profile, contributing to restricting the inflammatory process. The most important finding is that upregulation of seric XO activity leads to an excessive formation of uric acid, which contributes to oxidative and inflammatory processes. Moreover, uric acid induces the release of pro-inflammatory and pro-oxidative mediators, such NOx and ROS, which contribute directly to disease pathogenesis. In summary, the upregulation of XO activity may be considered a pathway involved in NOx and ROS production in silver catfish infected with I. multifiliis.

Xanthine oxidase activity exerts pro-oxidative and pro-inflammatory effects in serum of silver catfish fed with a diet contaminated with aflatoxin B1.

Several studies have associated the involvement of xanthine oxidase (XO) activity, a source of uric acid and reactive oxygen species (ROS), to pro-oxidative and pro-inflammatory effects during pathological conditions. Considering this, the aim of this study was to evaluate whether upregulation on seric XO activity may be a pathway involved in the oxidative stress in fish exposed to a diet contaminated with aflatoxin B1 (AFB1 ), as well as whether it may be considered a pathway involved in ROS and NOx production. Xanthine oxidase activity, as well as the uric acid, ROS and NOx levels increased in serum of fish fed with a AFB1 -contaminated diet on days 14 and 21 post-feeding compared to fish fed with a basal diet. Based on these evidences, upregulation of seric XO activity induces pro-oxidant and pro-inflammatory profiles in serum of fish fed with a AFB1 -contaminated diet due to excessive formation on uric acid. Also, the excessive uric acid induces the release of pro-oxidant and pro-inflammatory mediators, as ROS and NOx, also contributing to oxidative and inflammatory profiles. In summary, the upregulation on seric XO activity may be considered a pathway involved in the oxidative stress of fish exposed to a diet contaminated with AFB1 .

Involvement of xanthine oxidase inhibition with the antioxidant property of nanoencapsulated Melaleuca alternifolia essential oil in fish experimentally infected with Pseudomonas aeruginosa.

Nanoencapsulated Melaleuca alternifolia essential oil (tea tree oil, TTO) is a natural alternative treatment, with 100% therapeutic efficacy in fish experimentally infected with Pseudomonas aeruginosa, and has also potent protective effects linked with antioxidant properties. However, the pathways responsible for the antioxidant capacity remain unknown. Thus, this study evaluated whether the inhibition of seric xanthine oxidase (XO) activity can be considered a pathway involved in the antioxidant capacity of nanoencapsulated TTO in fish experimentally infected with P. aeruginosa. Seric samples from fish infected with P. aeruginosa showed increased XO activity, as well as increased uric acid and reactive oxygen species (ROS) levels. In contrast, the prophylactic treatment with nanoencapsulated TTO prevented these infection-induced alterations. Based on the evidence obtained, the upregulation of seric XO activity induced pro-oxidative effects in the serum of fish experimentally infected with P. aeruginosa, due to excessive formation of uric acid, which stimulates the release of ROS. This treatment was able to prevent the upregulated seric XO activity and, consequently, the excessive formation of uric acid and ROS. In summary, inhibition of seric XO activity can be considered a pathway involved in the antioxidant capacity of nanoencapsulated TTO in fish experimentally infected with P. aeruginosa.

Correlation of adipokines and markers of oxidative stress in women with gestational diabetes mellitus and their newborns.

AIM: We have shown that some markers of oxidative stress were higher in women with gestational diabetes mellitus (GDM). This study examines the relationship between adipokines and oxidative stress and their potential effects in pregnant women. METHODS: Three markers of oxidative stress (malondialdehyde, 8-isoprostane and xanthine oxidase) and three adipokines (leptin, adiponectin and resistin) were measured in maternal plasma, cord plasma and placenta of 208 pregnant women. RESULTS: Among all these women, 105 were diagnosed with GDM while the other 103 were controls. Leptin, resistin, malondialdehyde, xanthine oxidase and 8-isoprostane in maternal plasma, cord plasma and placenta were significantly higher while maternal adiponectin significantly lower in women with GDM (P < 0.05). Adipokines in maternal plasma, cord plasma and placenta were positively correlated with markers of oxidative stress. Both markers of oxidative stress and adipokines were correlated inversely with homeostasis model assessment of insulin resistance whereas positively with quantitative insulin sensitivity check index (P < 0.01). Adiponectin is negatively correlated with leptin and resistin. Placental/cord leptin and cord resistin levels were higher in the macrosomia while maternal adiponectin level was lower (P < 0.05) than normal birthweight newborns. Both markers of oxidative stress and adipokines in maternal and cord plasma are negatively correlated with newborn birthweight (P < 0.05). CONCLUSION: Adipokines interact with markers of oxidative stress, both of which lead to insulin resistance, GDM and macrosomia. It has long been known that placenta involves in the development of GDM. Adipokines might participate in this process and need to be confirmed by further studies.

Hypouricemic Effect of 2,5-Dihydroxyacetophenone, a Computational Screened Bioactive Compound from Ganoderma applanatum, on Hyperuricemic Mice.

Searching novel hypouricemic agents of high efficacy and safety has attracted a great attention. Previously, we reported the hypouricemic effect of Ganoderma applanatum, but its bioactives, was not referred. Herein, we report the hypouricemic effect of 2,5-dihydroxyacetophenone (DHAP), a compound screened from Ganoderma applanatum computationally. Serum parameters, such as uric acid (SUA), xanthine oxidase (XOD) activity, blood urea nitrogen (BUN), and creatinine were recorded. Real-time reverse transcription PCR (RT-PCR) and Western blot were exploited to assay RNA and protein expressions of organic anion transporter 1 (OAT1), glucose transporter 9 (GLUT9), uric acid transporter 1 (URAT1), and gastrointestinal concentrative nucleoside transporter 2 (CNT2). DHAP at 20, 40, and 80 mg/kg exerted excellent hypouricemic action on hyperuricemic mice, reducing SUA from hyperuricemic control (407 ± 31 μmol/L, p < 0.01) to 180 ± 29, 144 ± 13, and 139 ± 31 μmol/L, respectively. In contrast to the renal toxic allopurinol, DHAP showed some kidney-protective effects. Moreover, its suppression on XOD activity, in vivo and in vitro, suggested that XOD inhibition may be a mechanism for its hypouricemic effect. Given this, its binding mode to XOD was explored by molecular docking and revealed that three hydrogen bonds may play key roles in its binding and orientation. It upregulated OAT1 and downregulated GLUT9, URAT1, and CNT2 too. In summary, its hypouricemic effect may be mediated by regulation of XOD, OAT1, GLUT9, URAT1, and CNT2.

The hypoxanthine-xanthine oxidase axis is not involved in the initial phase of clinical transplantation-related ischemia-reperfusion injury.

The hypoxanthine-xanthine oxidase (XO) axis is considered to be a key driver of transplantation-related ischemia-reperfusion (I/R) injury. Whereas interference with this axis effectively quenches I/R injury in preclinical models, there is limited efficacy of XO inhibitors in clinical trials. In this context, we considered clinical evaluation of a role for the hypoxanthine-XO axis in human I/R to be relevant. Patients undergoing renal allograft transplantation were included (n = 40) and classified based on duration of ischemia (short, intermediate, and prolonged). Purine metabolites excreted by the reperfused kidney (arteriovenous differences) were analyzed by the ultra performance liquid chromatography-tandem mass spectrometer (UPLCMS/MS) method and tissue XO activity was assessed by in situ enzymography. We confirmed progressive hypoxanthine accumulation (P < 0.006) during ischemia, using kidney transplantation as a clinical model of I/R. Yet, arteriovenous concentration differences of uric acid and in situ enzymography of XO did not indicate significant XO activity in ischemic and reperfused kidney grafts. Furthermore, we tested a putative association between hypoxanthine accumulation and renal oxidative stress by assessing renal malondialdehyde and isoprostane levels and allantoin formation during the reperfusion period. Absent release of these markers is not consistent with an association between ischemic hypoxanthine accumulation and postreperfusion oxidative stress. On basis of these data for the human kidney we hypothesize that the role for the hypoxanthine-XO axis in clinical I/R injury is less than commonly thought, and as such the data provide an explanation for the apparent limited clinical efficacy of XO inhibitors.

Serum glutathione peroxidase, xanthine oxidase, and superoxide dismutase activities and malondialdehyde levels in patients with Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). Oxidative stress has been hypothesized to play a major role in the development of PD in various studies. This study assessed to investigate oxidative and anti-oxidative status in PD patients. We evaluated oxidant/antioxidant status by measuring serum malondialdehyde (MDA) levels, xanthine oxidase (XO) activities, and activities of antioxidant enzymes, namely, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). The study included 29 patients with PD and 32 healthy subjects as controls. Comparison of oxidative parameters in the patient and control groups revealed significantly higher GSH-Px and XO activities in the patient group. Serum MDA and SOD activities in PD patients were not significantly different from the controls. MDA was negatively correlated with duration of the PD and positively with age of onset. There was a negative correlation between SOD and Hoehn and Yahr (H&Y) stage. According to these results, we suggest that oxidative stress may contribute to the development of PD.

Mechanism-based pharmacokinetic-pharmacodynamic modeling of salvianolic acid A effects on plasma xanthine oxidase activity and uric acid levels in acute myocardial infarction rats.

1. Salvianolic acid A (SalA) was found to attenuate plasma uric acid (UA) concentration and xanthine oxidase (XO) activity in acute myocardial infraction (AMI) rats, which was characterized with developed mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) model. 2. AMI was induced in rats by coronary artery ligation. Surviving AMI rats received a single intravenous dose of 5 mg/kg of SalA and normal saline. The plasma SalA concentrations were determined by HPLC-MS/MS method. The plasma UA concentrations were determined by HPLC method and plasma XO activity were measured spectrophotometrically. An integrated mathematical model characterized the relationship between plasma UA and SalA. 3. Pharmacokinetics was described using two-compartment model for SalA with linear metabolic process. In post-AMI rats, XO activity and UA concentrations were increased, while SalA dosing palliated this increase. These effects were well captured by using two series of transduction models, simulating the delay of inhibition on XO driven by SalA and UA elevation resulted from the multiple factors, respectively. 4. The effect was well described by the developed PK-PD model, indicating that SalA can exert cardiovascular protective effects by decreasing elevated plasma UA levels induced by AMI.

Gelatinases A and B and Antioxidant Enzyme Activity in the Early Phase of Acute Myocardial Infarction.

Oxidative stress plays important roles in the pathophysiology of acute myocardial infarction (AMI). The aim of this study was to investigate the correlation of the oxidative stress status and matrix metalloproteinase activity in AMI patients in comparison to controls. This study included 136 subjects: 68 patients with AMI (42 males/26 females; mean age 58.5 ± 10.5 years) and 68 controls (37 males/29 females; mean age 60.2 ± 12.4 years). Gelatinases A and B were assayed using gelatin zymography, enzyme activities were obtained spectrophotometrically. Gelatinase A and B activities were increased in the AMI patients' group compared to the control. Activities of serum superoxide dismutase (SOD) and xanthine oxidase (XO) were significantly higher in AMI patients (106.53 ± 23.45 U/l, P < 0.001 and 158.18 ± 29.59 U/l, P < 0.001) than in the control group (55.99 ± 10.79 U/l and 79.81 ± 7.93 U/l). The activity of catalase (CAT) in the sera of AMI patients was lower (271.31 ± 7.53 U/l, P < 0.005) than in the control group (305.94 ± 97.28 U/l). Plasma glutathione peroxidase (GPx) and glutathione reductase (GR) in AMI patients were significantly higher (582.47 ± 184.81 U/l, P < 0.001 and 59.64 ± 21.88 U/l, P < 0.001) than in the control group (275.32 ± 104.69 U/l and 47.71 ± 20.05 U/l). The present findings demonstrate activation of gelatinases A and B and oxidative stress markers in the early stage of AMI. Gelatinases, detected at high levels in AMI patients only, indicate their noticeable predisposition for becoming additional biomarkers of the early phase of AMI.

Effect of 1 Repetition Maximum, 80% Repetition Maximum, and 50% Repetition Maximum Strength Exercise in Trained Individuals on Variations in Plasma Redox Biomarkers.

Polotow, TG, Souza-Junior, TP, Sampaio, RC, Okuyama, AR, Ganini, D, Vardaris, CV, Alves, RC, McAnulty, SR, and Barros, MP. Effect of 1RM, 80%RM, and 50%RM strength exercise in trained individuals on variations in plasma redox biomarkers. J Strength Cond Res 31(9): 2489-2497, 2017-For decades, scientists have examined the participation of oxygen/nitrogen species in anaerobic-like exercises, especially weightlifting and resistance exercises. The balance between the production of oxyradicals and antioxidant responses during anaerobic-like exercises is essential to assure adaptation to the physiological benefits of strength training and to prevent chronic harmful effects. The aim of this study is to examine the hypothesis that different weight loads (1 repetition maximum (RM), 80%RM, and 50%RM) lifted until exhaustion could impose distinct oxidative insults and elicit diverse antioxidant responses in plasma of young trained subjects. Glucose (+10%), lactate (+65%), urea (+30%), free iron (+65%), reduced/oxidized glutathione (+14 and +23%, respectively), and xanthine oxidase activity (2.2-fold) significantly increased after the 1RM test, whereas plasma antioxidant capacity dropped by 37%. When lower weight loads were applied (80%RM and 50%RM tests), heme-iron (+15 and +20%, respectively) became the prevalent pro-oxidant, although glutathione responses were only detected after 80%RM (+14%). Lactate concentration in plasma continuously increased, by 2.9-fold (80%RM) and 3.6-fold higher (50%RM test). We demonstrated that 1RM tests significantly diminish the antioxidant capacity of plasma because of iron overload, whereas 80%RM tests require higher involvement of glutathione molecules to counteract heme-iron oxidative insult. Mild redox imbalances promoted by heme-iron were found in plasma after 50%RM. Although we did not observe overall changes in muscle damage in young trained subjects, we cannot exclude the need for specific antioxidant supplementation depending on the strength protocols applied, especially for less responsive groups, such as sedentary and elderly populations.

Antioxidative-oxidative balance in epilepsy patients on antiepileptic therapy: a prospective case-control study.

Oxidative stress has been implicated in various disorders, including epilepsy. The aim of this study was to investigate the oxidant and antioxidant status of patients with epilepsy using antiepileptic drugs regularly and to compare them with healthy subjects. We investigated serum catalase (CAT), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and xanthine oxidase (XO) levels in 58 epilepsy patients and 25 healthy controls. Patients were divided into polytherapy (n = 17) and monotherapy (n = 41) groups, and antioxidant status was compared between the two groups and controls. There was no significant difference between the patient and control groups in terms of age or gender (p > 0.05). The mean duration of illness in the patients was 14.8 years, and the mean duration of treatment was 11.4 years. Comparison of the patient and control groups in terms of oxidative stress and antioxidant defence parameters revealed significantly higher MDA, GSH-Px, XO and lower level of CAT, SOD levels (p < 0.05). There were no differences in CAT, MDA, GSH-Px or SOD levels between the monotherapy and polytherapy groups; but the XO level was higher in the monotherapy group (p < 0.05). Although the XO level was decreased by polytherapy, it was higher than in controls. Our study found significantly low level of antioxidants in patients with epilepsy as compared to control. Thus, antiepileptic treatment did not improve oxidative stress parameters. Furthermore, our results show that polytherapy does not change the situation as compared with monotherapy. Antioxidant replacement therapy may benefit these patients.

Oxidative stress in northern elephant seals: Integration of omics approaches with ecological and experimental studies.

Northern elephant seals experience conditions that increase oxidative stress (OS), including extended fasting, ischemia and hypoxia during breath-holds, and immune responses during colonial breeding. Increased OS is suggested by increases in tissue and plasma concentrations of pro-oxidant enzymes NADPH oxidase and xanthine oxidase (XO). Serum cortisol concentrations were positively associated with XO concentrations and damage markers. Elephant seals exhibit robust anti-oxidant responses as evidenced by increases in anti-oxidant enzymes in plasma and tissues. These responses were sufficient to prevent oxidative damage during breath-holds and extended fasts in juveniles. However, high rates of energy expenditure during breeding were associated with increased evidence for oxidative damage to lipids, proteins and DNA in adults. We integrated investigations of the fasting metabolome and muscle and blubber transcriptomes into our oxidative stress studies. Non-targeted metabolomics analysis of fasting seals identified 227 known metabolites in plasma, including those related to glutathione and purine metabolism. Changes in plasma metabolites suggested that glutathione biosynthesis increased during fasting in weaned pups but not in lactating females. We produced the first reference sequence for elephant seals by RNA sequencing of skeletal muscle and adipose tissue transcriptomes and de novo transcriptome assembly. We annotated muscle and adipose transcripts and identified thousands of genes, including potential mediators of OS. This resource provides elephant seal-specific gene sequences, complements existing metabolite and protein expression studies and provides tools for examining cellular responses to OS in a variety of contexts. We examined changes in tissue gene expression in response to experimental elevation of plasma cortisol. Responses included downregulation of Negative Regulator of Reactive Oxygen Species (NRROS) in muscle, a regulator that limits reactive oxygen species production by tissues. These tools provide novel views of the cellular and systemic mechanisms that enable seals to tolerate high levels of OS.

Circulating and myometrial markers of oxidative stress in pregnant women with fetal growth restriction.

AIM: The objective of this study was to identify the relationship between fetal growth restriction (FGR) and oxidative stress. The mechanisms that protect against oxidative stress in the local microenvironment were investigated by comparing the activities of the markers, both in the circulation and myometrium. MATERIALS AND METHODS: Myometrial tissue and serum levels of malondialdehyde (MDA), xanthine oxidase (XO), catalase (CAT) and superoxide dismutase (SOD) markers were measured in 20 FGR and 20 healthy pregnancies. RESULTS: The mean duration of gestation at delivery was shorter (P = 0003) and the mean birthweight was lower P < 0001) in the FGR study group compared with the control group, as expected. While MDA and CAT concentrations were higher in the serum (P < 0.02 and P < 0.01, respectively), but lower in the myometrial samples (P < 0.01) in the FGR versus the control group, XO and myometrial SOD values were comparable in both groups. CONCLUSIONS: Although our data demonstrated that FGR is associated with oxidative stress, the exact role and mechanism of the oxidant and antioxidant imbalance is obscure. We speculate that despite limited local synthesis of CAT, effective and efficient removal of MDA in the uterine environment explains high MDA and CAT serum concentrations in women with FGR. Alternatively, a well-functioning myometrial system could rescue the fetus from reactive oxygen species, as demonstrated by lowered MDA and depleted CAT resulting from hyperconsumption. Elevated serum MDA and CAT levels in the serum may reflect the 'spillover' of these markers from the uterus to the circulation.