Free radical production by azomethine H: Effects on pancreatic and hepatic tissues

The antimalarial properties of azomethine H represent the basis for its use as a chemotherapeutic agent. This work was carried out in order to verify the biological side effects of azomethine H and to clarify the contribution of reactive oxygen species (ROS) in this process. It was shown that azomethine H increased serum activities of amylase, alanine transaminase (ALT) and the TEARS concentrations, in rats. No changes were observed in glutathione peroxidase and catalase activities. The drug-induced tissue damage might be due to superoxide radicals (O-2(.-)), since Cu-Zn superoxide dismutase activities were increased by azomethine I-I treatment. This study allows tentative conclusions to be drawn regarding which reactive oxygen metabolites play a role in azomethine H activity. We concluded that (O-2(.-)) maybe produced as a mediator of azomethine H action.

Long-term toxicity following acute administration of nickel

Nickel compounds have high potential risk for the health of populations and for this reason their toxic effects should be urgently established. To determine the effect of nickel monosulfide in the muscle at the injection site on pancreatic, hepatic, and osteogenic lesions and the potential therapeutic effect of Cu-Zn superoxide dismutase (SOD), male Wistar rats received single intramuscular injections of nickel monosulfide (NiS - 7 mg Ni2+/Kg). A group of these experimental rats were injected intraperitoneally, with a single weekly dose of SOD covalently linked to polyethylene glycol (SOD-PEG). Rats were sacrificed at 2, 4, 6, and 8 months after Ni2+ injection. Nickel monosulfide produced tumors at the injection site. The increased phospholipid, alanine transaminase (ALT), alkaline phosphatase (ALP), and amylase levels in serum, in absence of SOD-PEG, reflected the toxic effects on pancreatic, hepatic, and osteogenic tissues of rats. SOD activity was increased in serum of rats receiving SOD-PEG throughout the experiment, and no significant difference was observed in biochemical parameters of control and experimental rats in presence of SOD- PEG. Superoxide radical generated by Ni2+ is of primary importance in the development of tumors at the injection site. Superoxide anion (O2 -) is also an important toxic intermediate with respect to hepatic, pancreatic, and osteogenic injury, since SOD-PEG has a potential therapeutic effect.

Dietary restriction and fibre supplementation: Oxidative stress and metabolic shifting for cardiac health

Dietary modification ought to be the first line of strategy in prevention of the development of cardiac disease. The purpose of this study was to investigate whether dietary restriction, dietary-fibre-enriched diet, and their interactions might affect antioxidant capacity and oxidative stress in cardiac tissue. Male Wistar rats (180-200 g; n = 10) were divided into four groups: control ad libitum diet (C), 50% restricted diet (DR), fed with fibre-enriched diet (F), and 50% restricted fibre-enriched diet (DR-F). After 35 days of the treatments, F, DR, and DR-F rats showed low cholesterol, LDL-cholesterol, and triacylglycerol, and high HDL-cholesterol in serum. The DR, DR-F, and F groups had decreased myocardial lipoperoxide and lipid hydroperoxide. The DR-F and F treatments increased superoxide dismutase and glutatione peroxidase (GSH-Px). The DR treatment increased GSH-Px and catalase activities. Dietary fibre beneficial effects were related to metabolic alterations. The F and DR-F groups showed high cardiac glycogen and low lactate dehydrogenase/citrate synthase ratios, indicating diminished anaerobic and elevated aerobic myocardial metabolism in these animals. There was no synergistic effect between dietary restriction and dietary fibre addition, since no differences were observed in markers of oxidative stress in the F and DR-F groups. Dietary fibre supplementation, rather than energy intake and dietary restriction, appears to be the main process retarding oxidative stress in cardiac tissue.

Toxicity of hypercaloric diet and monosodium glutamate: oxidative stress and metabolic shifting in hepatic tissue.

The present study examines the effects of a hypercaloric diet on hepatic glucose metabolism of young rats, with and without monosodium glutamate (MSG) administration, and the association of these treatments with evaluating markers of oxidative stress. Male weaned Wistar rats (21 days old) from mothers fed with a hypercaloric diet or a normal diet, were divided into four groups (n=6): control (C) fed with control diet; (MSG) treated with MSG (4 mg/g) and control diet; (HD) fed with hypercaloric diet and (MSG-HD) treated with MSG and HD. Rats were sacrificed after the oral glucose tolerance test (OGTT), at 45 days of treatments. Serum was used for insulin determination. Glycogen, hexokinase(HK), glucose-6-phosphatase(G6PH), lipid hydroperoxide, superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) were determined in liver. HD rats showed hypoglycemia, hyperinsulinemia, and high hepatic glycogen, HK and decreased G6PH. MSG and MSG-HD had hyperinsulinemia, hyperglycemia, decreased HK and increased G6PH in hepatic tissue. These animals had impaired OGTT. HD, MSG and MSG-HD groups had increased lipid hydroperoxide and decreased SOD in hepatic tissue. Hypercaloric diet and monosodium glutamate administration induced alterations in metabolic rate of glucose utilization and decreased antioxidant defenses. Therefore, the hepatic glucose metabolic shifting induced by HD intake and MSG administration were associated with oxidative stress in hepatic tissue.

Synergistic action of olive oil supplementation and dietary restriction on serum lipids and cardiac antioxidant defences

Caloric intake is higher than recommended in many populations. Therefore, enhancing olive oil intake alone may not be the most effective way to prevent cardiovascular diseases. The purpose of the present study was to analyse the association of olive oil and dietary restriction on lipid profile and myocardial antioxidant defences. Male Wistar rats (180-200 g, n = 6) were divided into 4 groups: control ad libitum diet (C), 50% restricted diet (DR), fed ad libitum and supplemented with olive oil (3 mL/(kg-day)) (OO), and 50% restricted diet and supplemented with olive oil (DROO). After 30 days of treatments, OO, DR, and DROO groups had increased total cholesterol and high-density lipoprotein cholesterol concentrations. DR and DROO animals showed decreased low-density lipoprotein cholesterol. DROO had the lowest low-density lipoprotein cholesterol concentration. Total lipids and triacylglycerols were raised by dietary restriction and diminished by olive oil. OO rats had higher myocardial Superoxide dismutase and lower catalase and glutathione peroxidase activities than C rats. DR and DROO showed enhanced cardiac Superoxide dismutase, catalase, and glutathione peroxidase activities from the control. Olive oil supplementation alone improved the lipid profile but was more effective when coupled with dietary restriction. There was a synergistic beneficial action of dietary restriction and olive oil on serum lipids and myocardial antioxidant defences.

Effects of olive oil and its minor constituents on serum lipids, oxidative stress, and energy metabolism in cardiac muscle

Recent lines of evidence suggest that the beneficial effects of olive oil are not only related to its high content of oleic acid, but also to the antioxidant potential of its polyphenols. The aim of this work was determine the effects of olive oil and its components, oleic acid and the polyphenol dihydroxyphenylethanol (DPE), on serum lipids, oxidative stress, and energy metabolism on cardiac tissue. Twenty four male Wistar rats, 200 g, were divided into the following 4 groups (n = 6): control (C), OO group that received extra-virgin olive oil (7.5 mL/kg), OA group was treated with oleic acid (3.45 mL/kg), and the DPE group that received the polyphenol DPE (7.5 mg/kg). These components were administered by gavage over 30 days, twice a week. All animals were provided with food and water ad libitum The results show that olive oil was more effective than its isolated components in improving lipid profile, elevating high-density lipoprotein, and diminishing low-density lipoprotein cholesterol concentrations. Olive oil induced decreased antioxidant Mn-superoxide dismutase activity and diminished protein carbonyl concentration, indicating that olive oil may exert direct antioxidant effect on myocardium. DPE, considered as potential antioxidant, induced elevated aerobic metabolism, triacylglycerols, and lipid hydroperoxides concentrations in cardiac muscle, indicating that long-term intake of this polyphenol may induce its undesirable pro-oxidant activity on myocardium. © 2006 NRC Canada.

A preliminary differential proteomic analysis of the periplasmic fraction in Acidithiobacillus ferrooxidans planktonic and attached cells exposed to chalcopyrite

The Acidithiobacillus ferrooxidans periplasmic space is known to have proteins involved in the respiratory chains. There are no reports about the expression of the periplasmic proteins in A. ferrooxidans cells attached to chalcopyrite. In this preliminary work, it was compared the periplasmic protein profiles of A. ferrooxidans planktonic and attached cells after exposure to chalcopyrite for 2 hours. The bacterial response to chalcopyrite was investigated by a proteomic approach (two- dimensional gel electrophoresis and mass spectrometry). Four proteins differentially expressed between planktonic and attached cells after exposure to chalcopyrite were identified. Two of these proteins, repressed in chalcopyrite- attached cells, were both identified as superoxide dismutase, whereas the single strand binding protein (SSB) and the PspA/IM30 protein were induced. These results showed that A. ferrooxidans chalcopyrite- attached and planktonic cells show differential expression of the periplasmic proteins and that a proteomic approach can provide a valuable tool to detect proteins related to the A. ferrooxidans response to attachment to the mineral substrates. © (2009) Trans Tech Publications.

Possible mechanism by which zinc protects the testicular function of rats exposed to cigarette smoke

Background: The aim of this study was to evaluate the changes in testicular function of rats due to cigarette smoke exposure and the possible mechanism by which zinc protects against these alterations. Methods: MaleWistar rats (60 days old) were randomly divided into 3 groups: control (G1, n = 10); exposed to cigarette smoke (G2, n = 10; 20 cigarettes/day/9 weeks) and exposed to cigarette smoke and supplemented with zinc (G3, n = 8; 20 cigarettes/day/9 weeks; 20 mg/kg zinc chloride daily for 9 weeks, by gavage). After the treatment period, the animals were euthanized, and materials were collected for analyses. Results: G2 rats showed a reduction in body mass; impaired sperm concentration, motility, morphology and vitality; and increased malonaldehyde and thiol group levels and superoxide dismutase activity as compared to G1. Zinc prevented the reduction of sperm concentration and the excessive increase of lipid peroxidation and induced an increase in plasma testosterone levels, wet weight of testis and thiol group concentration. Conclusions: Exposure to cigarette smoke led to harmful effects on testicular function at least partially due to the exacerbation of oxidative stress. Supplementary zinc had an important modulator/protector effect on certain parameters. The mechanism of zinc protection can be through an increase of SH concentration. Thus, zinc supplementation may be a promising addition to conventional treatments for male infertility related to smoking. Copyright © 2012 by Institute of Pharmacology Polish Academy of Sciences.

Antioxidant enzyme activity and hydrogen peroxide content during the drying of Arabica coffee beans

The development of the germination process and drought stress during the drying of coffee can generate reactive oxygen species, which can be neutralized by way of antioxidant mechanisms. No studies related to antioxidant enzymes during the drying of coffee were found in the literature, and considering their importance, the enzymatic activities of superoxide dismutase (SOD), guaiacol peroxidase (GPOX) and glutathione reductase (GR), and also the hydrogen peroxide content were evaluated during the drying of two types of coffee bean, one processed as natural coffee and the other as pulped natural coffee. The results showed a reduction in the SOD, GPOX and GR enzymatic activities of the natural coffee as compared to the pulped natural coffee during the drying period. Moreover, the hydrogen peroxide content of the natural coffee was greater than that of the pulped natural coffee. These results suggest the development of oxidative stress during the coffee drying process, controlled more efficiently in pulped natural coffee by the early action of GPOX during the drying process. Nevertheless, differential responses by SOD isoenzymes and possibly the role of other peroxidases also appear to be involved in the responses observed. © 2013 Springer-Verlag Berlin Heidelberg.

Gastroprotective mechanisms of the chloroform and ethyl acetate phases of Praxelis clematidea (Griseb.) R.M.King & H.Robinson (Asteraceae)

Flavonoid-rich Praxelis clematidea (Griseb.) R.M.King & H.Robinson (Asteraceae) is a native plant of South America. This study evaluates the gastroprotective activity and possible mechanisms for both the chloroform (CHCl3P) and ethyl acetate phases (AcOEtP) obtained from aerial parts of the plant. The activity was investigated using acute models of gastric ulcer. Gastric secretion biochemical parameters were determined after pylorus ligature. The participation of cytoprotective factors such as mucus, nitric oxide (NO), sulfhydryl (SH) groups, prostaglandin E2 (PGE 2), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), reduction of lipid peroxidation (malondialdehyde level), and polymorphonuclear infiltration (myeloperoxidase activity), was also investigated. CHCl3P (125, 250, and 500 mg/kg) and AcOEtP (62.5, 125, and 250 mg/kg) showed significant gastroprotective activity, reducing the ulcerative index by 75, 83, 88 % and 66, 66, 81 % for ethanol; 67, 67, 56 % and 56, 53, 58 % for a non-steroidal anti-inflammatory drug (NSAID); and 74, 58, 59 % and 64, 65, 61 % for stress-induced gastric ulcer, respectively. CHCl3P (125 mg/kg) and AcOEtP (62.5 mg/kg) significantly reduced the ulcerative area by 78 and 83 %, respectively, for the ischemia-reperfusion model. They also did not alter the biochemical parameters of gastric secretion, the GSH level or the activities of SOD, GPx or GR. They increased the quantity of gastric mucus, not dependent on NO, yet dependent on SH groups, and maintained PGE2 levels. The P. clematidea phases demonstrated gastroprotective activity related to cytoprotective factors. © 2012 The Japanese Society of Pharmacognosy and Springer.

Diabetes mellitus triggers oxidative stress in the liver of alloxan-treated rats: A mechanism for diabetic chronic liver disease

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Genotoxic evaluation of the antimalarial drugs artemisinin and artesunate in human HepG2 cells and effects on CASP3 and SOD1 gene expressions

The malaria treatment recommended by the World Health Organization involves medicines derived from artemisinin, an active compound extracted from the plant Artemisia annua, and some of its derivatives, such as artesunate. Considering the lack of data regarding the genotoxic effects of these compounds in human cells, the objective of this study was to evaluate the cytotoxicity and genotoxicity, and expressions of the CASP3 and SOD1 genes in a cultured human hepatocellular liver carcinoma cell line (HepG2 cells) treated with artemisinin and artesunate. We tested concentrations of 2.5, 5, 7.5, 10, and 20 μg/mL of both substances with a resazurin cytotoxicity assay, and the concentrations used in the genotoxicity experiments (2.5, 5, and 10 μg/mL) and gene expression analysis (5 mg/mL) were determined. The results of the comet assay in cells treated with artemisinin and artesunate showed a significant dosedependent increase (P < 0.001) in the number of cells with DNA damage at all concentrations tested. However, the gene expression analysis revealed no significant change in expression of CASP3 or SOD1. Our data showed that although artemisinin and artesunate exhibited genotoxic effects in cultured HepG2 cells, they did not significantly alter expression of the CASP3 and SOD1 genes at the doses tested. ©FUNPEC-RP.

Metabolic profile and genotoxicity in obese rats exposed to cigarette smoke

Objective Experimental studies have shown that exposure to cigarette smoke has negative effects on lipid metabolism and oxidative stress status. Cigarette smoke exposure in nonpregnant and pregnant rats causes significant genotoxicity (DNA damage). However, no previous studies have directly evaluated the effects of obesity or the association between obesity and cigarette smoke exposure on genotoxicity. Therefore, the aim of the present investigation was to evaluate DNA damage levels, oxidative stress status and lipid profiles in obese Wistar rats exposed to cigarette smoke. Design and Methods Female rats subcutaneously (sc) received a monosodium glutamate solution or vehicle (control) during the neonatal period to induce obesity. The rats were randomly distributed into three experimental groups: control, obese exposed to filtered air, and obese exposed to tobacco cigarette smoke. After a 2-month exposure period, the rats were anesthetized and killed to obtain blood samples for genotoxicity, lipid profile, and oxidative stress status analyses. Results The obese rats exposed to tobacco cigarette smoke presented higher DNA damage, triglycerides, total cholesterol, free fatty acids, VLDL-c, HDL-c, and LDL-c levels compared to control and obese rats exposed to filtered air. Both obese groups showed reduced SOD activity. These results showed that cigarette smoke enhanced the effects of obesity. Conclusion In conclusion, the association between obesity and cigarette smoke exposure exacerbated the genotoxicity, negatively impacted the biochemical profile and antioxidant defenses and caused early glucose intolerance. Thus, the changes caused by cigarette smoke exposure can trigger the earlier onset of metabolic disorders associated with obesity, such as diabetes and metabolic syndrome. Copyright © 2012 The Obesity Society.

Avaliação das estruturas químicas derivadas de diaminas do ferroceno no metabolismo oxidativo em cepas de Trypanosoma cruzi

Pós-graduação em Biociências e Biotecnologia Aplicadas à Farmácia - FCFAR

Avaliação de biomarcadores de contaminação em tilápias do nilo (oreochromis niloticus) expostas aos herbicidas combine *500sc (tebutiurom) e velpar k® wg (diurom + hexazinona)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)