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Malathion is an organophosphate insecticide used in agriculture and for controlling vector-borne diseases such as Zika. Humans can be exposed to malathion by means of ingestion of contaminated food. The juvenile and peripubertal periods are a large window of vulnerability to the action of toxic agents. The aim of the present study was to evaluate the effects of low doses of malathion during the development of testes in the juvenile and peripubertal periods in rats. For this purpose, 45 male Wistar rats (postnatal day (PND) 25) were assigned to 3 experimental groups and treated for 40 days. The animals were exposed daily to malathion 10 mg/kg (M10 group) or 50 mg/kg (M50 group) diluted in 0.9 % saline via gavage. The control group received only the vehicle. On the 40th experimental day, the rats were anaesthetized and euthanized. The blood was collected for determination of testosterone concentration. The testes were removed and weighed. Spermatozoa from the vas deferens were used for sperm morphological analysis. The testes were used for evaluation of sperm count and oxidative stress status to determine the inflammatory profile and analysis of tissue constitution. The results showed that both malathion doses reduced the sperm count and increased the number of abnormal sperms. Furthermore, both doses altered the spermatogenetic process, delayed spermiogenesis, reduced the Leydig and Sertoli cell number and increased the thickness of tunica albuginea. The M10 group presented increased IL-10 levels and reduced GSH levels. These parameters did not change in the M50 group. However, the M50 group showed an increase in the number of abnormal seminiferous tubules, a decrease in plasma testosterone concentration and an increase in lipid peroxidation in the testes. In conclusion, the exposure to low doses of malathion during juvenile and peripubertal development resulted in testicular toxicity and compromised the testicular morphology and function.

Objective The aim of this study was to investigate the effects of creatine supplementation on early stages of ethanol-induced hepatic damage. Methods Male Swiss mice were divided into three groups (n = 12/group): control (C), ethanol (E), and ethanol supplemented with creatine (EC). The control group received a diet containing 15.8% of total calories from proteins, 46.3% from carbohydrates, and 37.9% from lipids. The ethanol and ethanol and creatine groups received diets containing 15.8% of total calories from proteins, 16.2% from carbohydrates, and 34.5% from lipids; the remaining calories were obtained from the addition of 5% of 95% ethanol. Creatine (1%; weight/vol) was added to the diet of EC mice. After 14 and 28 d, six animals from each group were sacrificed, generating subdivisions in each group: C14 and C28, E14 and E28, EC14 and EC28. After sacrifice, the liver was removed, weighed, and prepared for histologic, biochemical, and molecular analysis, and blood was collected. Results Ethanol intake induced mild cell degeneration, liver damage, oxidative lesions, and inflammation. Surprisingly, ethanol intake combined with creatine exacerbated cell degeneration and fat accumulation, hepatic expression of genes related to ethanol metabolism, oxidative stress and inflammation, and promoted oxidative stress and elevated plasma alanine aminotransferase (P Conclusion Creatine supplementation associated with ethanol is able to interfere in the alcohol metabolism and oxidative stress and to exacerbate ethanol-induced hepatic damage. These new findings are opposite to those observed in several studies where protective effects of creatine in a wide variety of injury models, including non-alcoholic fatty liver disease, were described.

The rostral ventrolateral medulla (RVLM) is the main sympathetic output of the central nervous system to control blood pressure. Reportedly, reactive oxygen species (ROS) can increase arterial pressure, leading to hypertension. As ROS increase the sympathetic tone in RVLM and obese animals present grater oxidative stress, it would be important to note this relationship.Therefore, we evaluated the systemic and central effects (in the RVLM) of vitamin C (vit C, an antioxidant) on the redox balance and cardiovascular and autonomic profiles in hyperadipose male rats. We also evaluated the neurotransmission by L-glutamate (L-glu) and vit C in the RVLM of awake hyperadipose rats.Our study confirmed that hyperadipose rats were hypertensive and tachycardic, presented increased sympathetic and decreased parasympathetic modulation of the heart, and had increased plasma lipoperoxidation compared with the control rats (CTR). Oral vitamin C treatment reverted cardiovascular, autonomic, and plasma redox dysfunction. Hyperadipose rats presented a higher blood pressure increase after L-glu microinjection and a lower response to vit C in the RVLM compared with the CTR group. Biochemical analysis of redox balance in RVLM punches showed that hyperadipose rats have increased NBT and T-BARS, and after treatment with vit C, the oxidative profile decreased. The antioxidative activity of vit C reduced the amount of ROS in the RVLM area that might have resulted in lowered blood pressure and sympathetic modulation.Our data suggest central and peripheral benefits of vit C treatment on cardiovascular, autonomic, and oxidative dysfunctions in hyperadipose animals.

Diabetes mellitus is a syndrome with multiple etiologies, characterized by chronic hyperglycemia that increases the production of reactive oxygen species and decreases antioxidant defenses. The present study evaluated oxidative stress parameters and protein nitration in myenteric neurons in the jejunum in diabetic rats supplemented with l -glutathione. Rats (90 days of age) were distributed into four groups (n = 6/group): normoglycemic (N), normoglycemic supplemented with l -glutathione (NGT), diabetic (D), and diabetic supplemented with l -glutathione (DGT). At 210 days of age, the animals were sacrificed, and the jejunum was collected, washed, and subjected to various procedures: tert-butyl hydroperoxide chemiluminescence (CL), determination of total antioxidant capacity (TAC), determination of catalase activity, quantification of nitric oxide (NO), and double-labeling of HuC/D-immunoreactive myenteric neurons and nitrotyrosine (3-NT). Diabetes increased oxidative stress in the jejunum in the D group, reflected by increases in lipid peroxidation, TAC, catalase activity, and NO. The D group exhibited an increase in the percentage of myenteric neurons that were double-labeled with 3-NT. Supplementation with l -glutathione did not cause differences in the average CL curves between the D and DGT groups, but reductions of TAC and catalase activity were observed. Supplementation with l -glutathione promoted a reduction of neurons that contained 3-NT in the DGT group. Diabetes mellitus promoted oxidative stress in the jejunum, and supplementation with l -glutathione improved oxidative status by preventing protein nitration in myenteric neurons in diabetic animals that received supplementation.

The aim of this study was to investigate changes in homocysteine (Hcy) metabolism and redox balance in response to exercise treatment in a tumor-bearing rat model.Male Wistar rats were exposed, or not, to a resistance exercise program 6 wk before inoculation with Walker-256 tumor cells or vehicle. After application, rats maintained their routine for 12 d and were then sacrificed for plasma and liver analyses.Impaired Hcy metabolism was evident after 12 d of tumor cell inoculation as demonstrated by significantly increased (P 0.05) plasma total homocysteine (tHcy) concentration (53%) and decreased plasma cysteine, methionine, and vitamin B12 concentrations. Decreased hepatic cystathionine β-synthase (CBS) and betaine-homocysteine S-methyltransferase mRNA levels were found in tumor-bearing rats but not in controls. Tumor inoculation also decreased levels of liver reduced glutathione (GSH) and increased hepatic oxidative stress compared with non-tumor controls. However, resistance exercise prevented the tumor-impaired transsulfuration pathway as demonstrated by the decreased plasma tHcy, hepatic CBS expression, and increased GSH in tumor-exercised versus tumor-sedentary rats. Remarkably, all measures of liver oxidative stress were suppressed by exercise training. Tumor weight was unchanged between groups.Resistance exercise prevented tHcy accumulation and liver oxidative damage caused by Walker-256 tumor cell inoculation; the modulatory effects of resistance exercise on Hcy metabolism appear to be at the level of transsulfuration pathway.

Aims Well-characterized animal tumor models of cancer cachexia are warranted to elucidate underlying mechanisms and provide a better approach to the human scenario. We aimed to investigate whether solid Ehrlich carcinoma reproduces clinical, functional and biological conditions of tumor-induced cachexia in mice. Methods Eight-week old female Swiss mice were subcutaneously inoculated with Ehrlich tumor cells (tumor-bearing, TB group) or vehicle (sham) into the right flank and monitored for 28 days. Tumor histopathological features and tumor–host interaction, including tissue weight, muscle structure, strength and biochemical parameters were carried out. Key findings Tumor growth curve demonstrated a linear pattern with no difference in final carcass weight between groups. A well-defined capsule composed by connective tissue infiltrated by inflammatory and neoplastic cells surrounded the tumors. The TB group had reduced handgrip strength, aside from lower cross sectional area (CSA) and critically reduced parametrial fat pads. Plasma parameters of lactate dehydrogenase (LDH), creatine kinase (CK) and tumor necrosis factor-α (TNF-α) were higher in the TB group, suggesting predominance of catabolic and pro-inflammatory activities. Conversely, food intake and tissue weight did not differ between groups. Significance Our data elucidated that the solid Ehrlich tumor model is feasible and effective in reproducing some of the relevant issues experienced by cancer patients with cachexia. The solid Ehrlich carcinoma emerges as an alternative tool against more aggressive cancer cachexia models during preclinical research.

Malignant melanoma is the most dangerous form of skin cancer. Despite new therapies for melanoma treatment, effective therapy is mainly limited by excessive metastasis. Currently, the factors determining metastasis development are not elucidated, but oxidative stress was suggested to be involved. To this end, we analyzed oxidative stress parameters during the metastatic development using the syngeneic B16F10 melanoma model. An increase in blood plasma lipid peroxidation occurred at the earliest stage of the disease, with a progressive decrease in oxidative damage and an increase in antioxidant defense. Vice versa, increased lipid peroxidation and 3-nitrotyrosine, and decreased antioxidant parameters were observed in the metastatic nodules throughout the disease. This was concomitant with a progressive increase in vascular endothelial growth factor and proliferating cell nuclear antigen. We conclude that the oxidative stress in the bloodstream decreases during the metastatic process and that nitrosative stress increases during the proliferation and growth of metastatic nodules in the tumor microenvironment. These results will help to better understand the role of oxidative stress during melanoma metastasis.

Considering the antioxidant, neuroprotective, inflammatory and nitric oxide modulatory actions of quercetin, the aim of this study was to test the effect of quercetin administration in drinking water (40 mg/day/rat) on neuronal nitric oxide synthase (nNOS), vasoactive intestinal peptide (VIP), overall population of myenteric neurons (HuC/D) and nitric oxide (NO) levels in the jejunal samples from diabetic rats. Male Wistar rats were distributed into four groups (8 rats per group): euglycemic (E), euglycemic administered with quercetin (E+Q), diabetic (D) and diabetic administered with quercetin (D+Q). Rats were induced to diabetes with streptozotocin (35mg/kg/iv) and, after 120 days, the proximal jejunum were collected and processed for immunohistochemical (VIP, nNOS and HuC/D) and chemiluminescence (quantification of tissue NO levels) techniques. Diabetes mellitus reduced the number of nNOS-IR (immunoreactive) (p 0.05) and HuC/D-IR (p 0.001) neurons, however, promoted an increased morphometric area of nNOS-IR neurons (p 0.001) and VIP-IR varicosities (p0.05). In D+Q group, neuroplasticity effects were observed on HuC/D-IR neurons, accompanied by a reduction of cell body area of neurons nNOS- and VIP-IR varicosities (p 0.05). The NO levels were increased in the E+Q (p 0.05) and D+Q group (p 0.001) compared to the control group. In conclusion, the results showed that quercetin supplementation increased the bioavailability of NO in the jejunum in euglycemic and mitigate the effects of diabetes on nNOS-IR neurons and VIP-IR varicosities in the myenteric plexus of diabetic rats.

Chronic consumption of ethanol causes morphological and physiological changes in the reproductive system of mammals. Vitamin C has an antioxidant role in organisms by neutralizing the ROS (reactive oxygen species) produced by oxidizing agents and this vitamin has an important function in the male reproductive system. The aim of this study was to evaluate whether vitamin C could prevent or attenuate the alterations in the male reproductive system caused by ethanol consumption. To test this hypothesis, male rats were divided into three experimental groups and treated by gavage for 63 days. The ethanol (E) and ethanol+vitamin C (EC) groups received 2 g/kg of ethanol (25%v/v) daily. In addition to ethanol, the EC group received vitamin C at a dose of 100 mg/day, diluted in water. The control group (C) received only the vehicle. On the 64th experimental day, the animals were anesthetized and euthanized, and blood was collected for plasmatic hormonal analysis. The testis, epididymis, vas deferens, and seminal vesicles were removed and weighed. Sperm from the vas deferens was submitted to morphological and motility analysis. The testis and epididymis were used for oxidative stress and histopathological analysis, sperm count, morphometric analysis of the testis, and stereological analysis of the epididymis. The results showed that vitamin C has a protective effect in the testes of adult male rats, entirely normalizing the parameters of sperm count, spermatogenesis kinetics, lipid peroxidation levels, and sperm motility, as well as partially normalizing the histopathological damage in the testis, epididymis, and sperm morphology. Thus, we concluded that lipid peroxidation is a major mechanism by which ethanol affects the testes and sperm, whereas no plasmatic testosterone alterations were found.

Overexpression of human epithelial growth factor receptor 2 (HER2) is a poor prognostic factor in breast cancer. HER2 is a transmembrane receptor comprising an extracellular domain (ECD), a single transmembrane domain, and an intracellular domain (ICD) with tyrosine-kinase activity. Receptor dimerization triggers pivotal effector pathways in cancer, such as phosphatidylinositol 3-kinase (PI3K) signaling. Currently, screening of HER2 in breast tumors for prognostic and therapeutic purposes involves immunohistochemical (IHC) phenotyping for the ECD, in which tumors with IHC scores below 2+ are reported as HER2-negative. We used a label-free liquid chromatography–mass spectrometry (LC–MS) proteomic approach to compare plasma samples from patients with HER2-positive breast tumors and patients with HER2-negative tumors. Patients with HER2-negative tumors expressed higher circulating levels of calpain-10 than patients with HER2-positive tumors. Calpains cleave HER2, releasing its ECD and transforming phenotypically positive tumors into phenotypically negative tumors. Therefore, we investigated the expression of the ICD in HER2-negative samples that overexpressed calpain-10. We found that 16% of HER2-negative tumors were positive for HER2-ICD, which was associated with circulating HER2-ECD. HER2 gene amplification was also observed in some HER2-negative tumors. Positive staining for the PI3K pathway was observed in the HER2-negative, ICD-positive tumors, similar to the HER2-positive cohort. Microarray analysis revealed that HER2-negative, ICD-positive samples clustered between HER2-positive tumors and triple-negative tumors. Survival analysis revealed that outcome in women with HER2-negative, ICD-positive tumors was better than in women bearing HER2-negative, ICD-negative (triple negative) tumors but was quite similar to HER2-positive tumors and worse than women with luminal A tumors. Moreover, in vitro analyses revealed that MDA-MB 231, a triple negative cell line, possesses calpain-10 and HER2-p-ICD up-regulation and blockage of calpain-10 activity promoted an increase in HER2-p-ICD and p-AKT levels, suggesting an increase in these pathways signaling. These data indicate that HER2-negative tumors with HER2-ICD positivity exhibit clinical behavior closer to that of HER2-positive tumors. This indicates a need for HER2-ICD screening when determining the molecular profile of breast tumors. These findings further indicate that lapatinib should be investigated as a target therapy for HER2-ICD-positive breast tumors.

Background Recent studies have suggested a regulatory role for some of the metabolites derived from oxidative stress in breast cancer. In this way, cancer-induced oxidative changes could modify the breast environment and potentially trigger systemic responses that may affect disease prognosis and recurrence. In this study, we investigated the systemic oxidative profile of women with early breast cancer bearing the primary tumor and after tumor withdrawal, and its long-term implications. Patients and Methods Plasma samples were collected at diagnosis, and the systemic oxidative profile was determined by evaluating the lipid peroxidation, total antioxidant capacity of plasma (TRAP), malondialdehyde (MDA), protein carbonylation, and hydroperoxides. Nitric oxide, vascular endothelial growth factor (VEGF), and tumor necrosis factor alpha (TNF-α) levels were further measured. We also evaluated the impact of the oxidative profiling at diagnosis on disease recurrence in a 5-year follow-up. Results Enhanced oxidative stress was detected in patients bearing the primary tumors, characterized by high lipid peroxidation, TRAP consumption, high carbonyl content, and elevated VEGF and TNF-α levels. After tumor removal, the systemic oxidative status presented attenuation in lipid peroxidation, MDA, VEGF, and TNF-α. The 5-year recurrence analysis indicated that all patients who recidivated presented high levels of lipid peroxidation measured by chemiluminescence at diagnosis. Conclusions Our data suggest that the presence of the primary tumor is indicative of the systemic pro-oxidant status of breast cancer and demonstrates a role for lipid peroxidation in disease recurrence, highlighting the need for a metabolic follow-up of patients with cancer at diagnosis before tumor removal.

Rosmarinic acid (RosmA) demonstrates antioxidant and anti-inflammatory properties. We investigated the effect of RosmA on liver ischemia/reperfusion injury. Rats were submitted to 60 min of ischemia plus saline or RosmA treatment (150 mg/kg BW intraperitoneally) followed by 6 h of reperfusion. Hepatocellular injury was evaluated according to aminotransferase activity and histological damage. Hepatic neutrophil accumulation was also evaluated. Oxidative/nitrosative stress was estimated by measuring the reduced glutathione, lipid hydroperoxide and nitrotyrosine levels. Endothelial and inducible nitric oxide synthase (eNOS/iNOS) and nitric oxide (NO) were assessed with immunoblotting and chemiluminescence assays. Hepatic tumor necrosis factor-alpha (TNF-α) and interleukin-1beta mRNA were assessed using real-time PCR, and nuclear factor-kappaB (NF-κB) activation was estimated by immunostaining. RosmA treatment reduced hepatocellular damage, neutrophil infiltration and all oxidative/nitrosative stress parameters. RosmA decreased the liver content of eNOS/iNOS and NO, attenuated NF-κB activation, and down-regulated TNF-α and interleukin-1beta gene expression. These data indicate that RosmA exerts anti-inflammatory and antioxidant effects in the ischemic liver, thereby protecting hepatocytes against ischemia/reperfusion injury. The mechanisms underlying these effects may be related to the inhibitory potential of RosmA on the NF-κB signaling pathway and the reduction of iNOS and eNOS expressions and NO levels, in addition to its natural antioxidant capability.

HIV-1 infection is accompanied by severe metabolic and immune dysfunction. The aim of this study was to evaluate the role of metabolic syndrome (MetS) and antiretroviral therapy (ART) utilization on the adiponectin levels and oxidative stress in patients infected with HIV-1.We allocated 285 patients into four groups: group 1: patients without MetS who were not using ART; group 2: patients without MetS using ART; group 3: patients with MetS who were not using ART; and group 4: patients with MetS using ART. Biochemical, immunologic, and oxidative stress parameters were measured.Group 4 exhibited higher lipoperoxides when compared with group 1 (P0.0001) and higher advanced oxidation protein products (AOPP) compared with group 2 or group 1 (P0.0001). Group 3 also presented higher AOPP than group 2 (P0.05). Group 4 showed lower adiponectin levels compared with groups 1 or 2 (P0.0001). Similarly, group 3 presented lower adiponectin levels compared with group 2 (P0.05) or group 1 (P0.0001). Multivariate analysis showed that both an increase in AOPP and a decrease in total radical-trapping antioxidant parameter/uric acid were independently associated with MetS in HIV-1 patients. Regarding immunologic markers of HIV-1 disease progression and viral replication, group 4 exhibited significantly higher CD45(+), CD3(+), and CD4(+) T cells count compared with group 2 (P0.01).HIV-1-infected patients with MetS exhibited hypoadiponectinemia and increased oxidative stress, and these findings were not influenced by ART use. The findings of the present study allow the suggestion that MetS and inflammation might be mainly responsible for the aforementioned features. More studies are needed to verify whether drugs or food, which yield increased adiponectinemia and decreased oxidative stress, could reduce cardiovascular risk in HIV-infected patients.

SummaryIntroductionSmoking cessation promotes health benefits and, despite cigarette smoking be an important pro inflammatory stimulus, there are few studies concerning the nasal and systemic inflammation; as well as the mucociliary clearance behavior in smokers after short period of smoking cessation.AimTo evaluate the nasal and systemic inflammatory markers and mucociliary clearance behavior after 30 days of cigarette smoking abstinence.MethodsTwenty-five smokers were included and divided into two groups: abstinent smokers (n = 14) and current smokers (n = 11). Tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-8 and IL-10 were measured on nasal lavage and blood serum samples by ELISA at baseline and after 30 days. The mucociliary clearance, exhaled carbon monoxide (exCO) and carboxyhemoglobin (HbCO) were also measured at the same moments.ResultsThere was a decrease of TNF-α level only in blood serum at 30 days of abstinence compared to current smokers. The mucociliary clearance improved and there was a reduction in exCO and HbCO (p

Although cardiac muscle hypertrophy has been studied in association with several diseases, its mechanism in patients with emphysema, in particular in relation to oxidative stress and proteolysis, remains unknown. The role of oxidative stress and proteolysis in right and left ventricle hypertrophy was investigated in hamsters with emphysema induced by 2 different doses of papain (20mg/mL, E20 and 40mg/mL, E40). The thickness of the ventricles, total and cardiac weight, lipid peroxidation, carbonyl proteins, total antioxidant capacity (TAC), and proteasomal proteolytic activity were evaluated in the right ventricle (RV) and the left ventricle (LV) of control and emphysema hamsters. RV thickness was increased by 12% in the E20 group and by 29% in the E40 group. Lipid peroxidation measured by chemiluminescence was increased in the E40 group (from 3350.68±392.44URL/g tissue to 4696.63±1076.70URL/g tissue, p

This study provides evidence that skin oxidative stress injury caused by UVB irradiation is mediated predominantly by reactive oxygen species immediately after irradiation and by reactive nitrogen species at later time points. Animals were pre-treated with free radical scavengers (deferrioxamine, histidine), α-tocopherol, or inhibitors of nitric oxide synthase (NOS) (L-NAME or aminoguanidine) or left untreated and subjected to UVB irradiation. α-Tocopherol inhibited the increase in lipid peroxidation, as evaluated by chemiluminescence at 0 h and 24 h after UVB irradiation. Immediately after UVB irradiation, lipid peroxidation increased moderately and was abolished by free radical scavengers but not by NOS inhibitors. Likewise, the reduction of antioxidant capacity was not reversed by NOS inhibitors. Nitric oxide augmentation was not observed at this time point. Twenty-four hours after irradiation, increased lipid peroxidation levels and nitric oxide elevation were observed and were prevented by NOS inhibitors. Low concentrations of GSH and reduced catalase activity were also observed. Altogether, these data indicate that reactive oxygen species (singlet oxygen and hydroxyl radicals) are the principal mediators of immediate damage and that reactive nitrogen species (*NO and possibly ONOO(-)) seem to be involved later in skin oxidative injury induced by UVB radiation. The reduced catalase activity and low level of GSH suggest that *NO and H(2)O(2) may react to generate ONOO(-), a very strong lipid peroxidant species.

Chagas' disease is accompanied by severe anemia and oxidative stress, which may contribute to mortality. In this study, we investigated the role of 5-lipoxygenase (5-LO) in the control of parasitism and anemia associated with oxidative damage of erythrocytes in experimental Trypanosoma cruzi infection. Wild-type C57BL/6, 129Sv mice treated or not with nordihydroguaiaretic acid (NDGA, 5-LO inhibitor), mice lacking the 5-LO enzyme gene (5-LO(-/-)) and inducible nitric oxide synthase gene (iNOS(-/-)) were infected with the Y strain of T. cruzi. Impairment of 5-LO resulted in increased numbers of trypomastigote forms in the blood and amastigote forms in the heart of infected mice. We assessed oxidative stress in erythrocytes by measuring oxygen uptake, induction time and chemiluminescence following treatment with tert-butyl hydroperoxide (TBH). Our results show that 5-LO metabolites increased lipid peroxidation levels in erythrocytes during the early phase of murine T. cruzi infection. NDGA treatment reduced oxidative damage of erythrocytes in C57BL/6 T. cruzi-infected mice but not in C57BL/6 iNOS(-/-) infected mice, showing that the action of NDGA is dependent on endogenous nitric oxide (NO). In addition, our results show that 5-LO metabolites do not participate directly in the development of anemia in infected mice. We conclude that 5-LO products may not only play a major role in controlling heart tissue parasitism, i.e., host resistance to acute infection with T. cruziin vivo, but in the event of an infection also play an important part in erythrocyte oxidative stress, an NO-dependent effect.

Metabolic syndrome (MS) is a cluster of risk factors for cardiovascular disease related mainly to insulin resistance, but also to oxidative stress. Uric acid and gamma-glutamyltransferase (GGT) levels are also associated with MS and oxidative stress. This study was undertaken to assess the role of GGT and uric acid in adult patients with MS and its relation to oxidative stress and antioxidant defense.A total of 88 adults (67 with MS and 21 controls) were selected among ambulatory patients and workers of the University Hospital of Londrina, Paraná, Brazil. Oxidative stress was assessed by determination of thiobarbituric acid-reactive substances and tert-butyl hydroperoxide-initiated chemiluminescence and antioxidant defenses by total radical-trapping antioxidant parameter.The MS group presented higher significant results (P0.0001) than the control group in all parameters of MS and uric acid and GGT levels and significant lower values (P0.0001) in high-density lipoprotein cholesterol levels. Thiobarbituric acid-reactive substances and total radical-trapping antioxidant parameter did not show statistically significant differences between groups. However, lipid hydroperoxides, evaluated by tert-butyl hydroperoxide-initiated chemiluminescence, showed higher significant results in the MS group (P = 0.045) than in the control group. Total antioxidant capacity did not decrease and thiobarbituric acid-reactive substances did not increase, probably due to increased uric acid (r = 0.239, P = 0.04) in the MS group.The present study confirmed that GGT is a strong predictor of MS and that lipid peroxide measured by tert-butyl hydroperoxide-initiated chemiluminescence and GGT activity are reliable markers of oxidative stress in this syndrome.

Objective: To evaluate the hypolipemic and antioxidant effects of soy and green tea alone and/or in association in dyslipidemic subjects. Methods: One hundred dyslipidemic individuals were allocated into four groups. The soy group ingested 50 g of soy (kinako) daily, and the green tea group ingeste d3g o fgreen tea in 500 mL of water per day. A third group ingested 50 g of soy an d3g o fgreen tea daily, and the control group had a hypocholesterolemic diet. Evaluations were performed at baseline and after 45 and 90 d. Plasma levels of total cholesterol, high-density lipoprotein, and triacylglycerols were evaluated by automated methods. Low-density lipoprotein (LDL) cholesterol was calculated using the Friedewald equation. LDL was isolated by ultracentrifugation. Total plasma antioxidant capacity and plasma levels of total lipid hydroperoxides and those linked to LDL were evaluated by chemiluminescence. The results were expressed as median values and their 25th to 75th percentiles, with a 5% level of significance. Results: No significant difference occurred in LDL, high-density lipoprotein cholesterol, and triacyl- glycerol levels across groups. However, a statistically significant difference in total cholesterol occurred within the soy/green tea group 45 and 90 d after intervention. No statistically significant difference occurred in plasma levels of lipid hydroperoxides or those linked to LDL in any of the groups studied. All the groups that used soy and/or green tea presented increased total plasma antioxidant potential. Conclusion: Soy and green tea, alone or in combination, increased the total antioxidant potential of hypercholesterolemic patients, whereas only the combination decreased total cholesterol levels. © 2008 Elsevier Inc. All rights reserved.

The mechanisms by which Pb(2+) induces hemolysis are not completely understood. For this reason, the involvement of oxidative stress in the mechanism of Pb(2+)-induced pre-hemolytic lesion was investigated by exposing RBC to Pb(2+) in vitro and then separating the intact non-hemolysed RBC. Oxidative stress was investigated on human RBCs by tert-butyl hydroperoxide-initiated chemiluminescence method (CL). Our results revealed that lead-induced time and concentration-dependent hemolysis and CL time curves showed a very narrow correlation each other. GSH oxidation to GSSG and the stress index also increased significantly. Treatment of lead-exposed RBC with desferrioxamine, an iron-chelating agent or the chain-breaking antioxidant, Trolox, quenched light emission and inhibited hemolysis dramatically. Mannitol and sodium formate, (*)OH scavengers, on the contrary, did not inhibit CL or hemolysis, significantly. These data indicate that lead-induced lipid peroxide formation is mediated by a metal-driven Fenton reaction but do not support the direct involvement of hydroxyl radicals in this process. By contrast, our results revealed a decrease in light emission and decreased hemolysis in the presence of histidine, a singlet oxygen scavenger. Our results suggest that membrane damage and hemolysis of RBC are mediated by Pb(2+) through free radical reactions and that singlet oxygen plays a significant role in this process.

The mutagenicity of interstitial water and organic extracts from the sediments in the Cadeia and Feitoria Rivers, RS, Brazil, were evaluated by Salmonella microsuspension bioassay using TA97a, TA98, TA100 and TA102 strains, in the absence and presence of S9 mix. At the contaminated site, the mutagenic responses for interstitial water, suggested the presence of frameshift and base pair substitution mutagens, including oxidative substances. Organic extracts presented direct or indicative mutagenesis to the TA97a, TA98 and TA100 strains. In general, an exogenous metabolic systems decreased the mutagenicity of the samples. High concentrations of total chromium found in the sediment and interstitial water as well as total mercury in the sediment of the contaminated site, when compared to the control area, may help explain the mutagenic results. The livers of Gymnogeophagus gymnogenys collected in this impacted area, compared to a non-polluted site, were analyzed for oxidative stress parameters. Compared to the controls, there was a significant increase in the activity of superoxide dismutase (SOD) at levels of substances reactive to thiobarbituric acid (TBARS), and in the chemiluminescence of hepatic cells in fish in the polluted area. The concentration of cytochromes P450 and b5 decreased drastically in the fish at the polluted site, while the catalase activity did not change. It was possible to correlate the biological changes in the fish with the presence of mutagenic compounds in sediment and interstitial water in this area.

The livers fractions of Oreochromis niloticus (Tilapia) and Wistar rats taken from treated animals to single intraperitoneal doses of hexavalent chromium (K(2)Cr(2)O(7)), were analyzed for tert butyl hydroperoxide-initiated chemiluminescence (CL), lipid peroxidation using thiobarbituric acid reactive substances (TBARS), enzymes superoxide dismutase (SOD) and catalase activities, and the quantification of cytochromes P450 and b5. The CL time course curve was significantly higher in O. niloticus treated with Cr(VI) at all times studied. The maximum CL was observed after 24h of exposure. The CL mean ratio treated/control was 4.6 and the initial velocity (V(0)) increased 7.4 times at 24h of intoxication. The TBARS levels however increased only 24h after intoxication. The CL time course curve was significantly higher in rats treated with Cr(VI) as early as 3h after intoxication. The maximum CL occurred 24h after exposure. The CL mean ratio treated/control was 2.1 and the V(0) increased 3.8 times at 24h of intoxication. On the contrary, was not observed any increase in TBARS in this study. Compared to the controls, in fish, SOD activity increased significantly only 24h after of exposure. In rats, there was a significant increase in SOD activity after 3 and 24h of intoxication. There was no catalase activity, nor cytochrome P450 and cytochrome b5 variation in both species studied. Through CL approach, it was possible to detect oxidative stress as early as 15min in fish and 3h in rats. Also a marked oxidative stress was revealed by the increased CL parameters that at 24h of intoxication was accompanied by arose SOD activity in liver of O. niloticus and Wistar rats and increased TBARS in O. niloticus. In addition, it was possible to show higher levels of oxidative stress in fish compared to the rat in spite of the dose to be four times smaller. Furthermore, CL provide a sensitive method for possible use to detect earlier biological impact in contaminated environments.

It has been proposed that beta-blockers and agents affecting Ca2+ metabolism might exert cardioprotective actions because of their ability to act as antioxidants in vivo. The feasibility of this proposal was tested by examining the reaction of a series of such compounds with various oxygen-derived species. None of the compounds tested was sufficiently reactive with superoxide radical, hydrogen peroxide or hypochlorous acid for scavenging of these species to be feasible in vivo at the drug concentrations present in patients given the usual therapeutic doses. All the drugs tested were powerful scavengers of hydroxyl radical except for flunarizine, which stimulated iron ion-dependent hydroxyl radical generation from hydrogen peroxide. However, none of the drugs significantly inhibited production of hydroxyl radicals in this system. Propranolol, verapamil and flunarizine had significant inhibitory effects on the peroxidation of rat liver microsomes in the presence of iron ions and ascorbic acid. All three compounds exerted weaker inhibitory effects on peroxidation of arachidonic acid caused by a mixture of myoglobin and H2O2: pindolol stimulated peroxidation in this system. It is concluded that the ability of beta-blockers and "Ca(2+)-blockers" to inhibit lipid peroxidation varies with the lipid substrate used and the mechanism by which peroxidation is induced. We conclude that suggestions that beta-blockers and "Ca(2+)-blockers" exert antioxidant effects in vivo are not well founded, although there is a possibility that verapamil and propranolol might have some inhibitory effects against peroxidation if they accumulate in membranes to a sufficiently-high concentration in vivo. We could not confirm the reported ability of propranolol to inhibit the enzyme xanthine oxidase.