Sílvio Terra Stefanello

Evaluation of in vitro antioxidant effect of new mono and diselenides

This study was designed to examine the antioxidant activity in vitro of novel mono- and diselenide compounds. We compared whether the formation of p-methyl-selenol from compounds 1-phenyl-3-(p-tolylselanyl)propan-2-amine (C1) and 1,2-dip-tolyldiselenide (C4) and o-methoxy-selenol from compounds 1-(2-methoxyphenylselanyl)-3-phenylpropan-2-amine (C2) and 1,2-bis(2-methoxyphenyl)diselenide (C3) may be involved in their antioxidant effects. The compounds were tested against Fe(II) and sodium nitroprusside (SNP)-induced lipid peroxidation in rat brain and liver homogenates. Likewise, the antioxidant capacity of the compounds was assessed by their ability to decolorize the DPPH radical as well as the Fe(II) chelating assay through the reduction of molybdenum(VI) (Mo6+) to molybdenum(V) (Mo5+). This colorimetric assay was also used to quantify thiol peroxidase (GPx) and oxidase activity and thioredoxin reductase (TrxR) activity. The results showed that the novel selenide compounds inhibit the thiobarbituric acid reactive species (TBARS) induced by different pro-oxidants, but the monoselenides effects were significant only at concentrations higher than the concentrations of the diselenides. Similarly, the total antioxidant activity was higher in the diselenides. Moreover, GPx and TrxR activity was only observed for the diselenides, which indicates that these compounds are more stable selenol molecules than monoselenides.

Antioxidant Activity and Phytochemical Composition of the Leaves of Solanum guaraniticum A. St.-Hil

Solanum guaraniticum is a shrub belonging to the Solanaceae family popularly known in Brazil as jurubeba or false-jurubeba. The aim of this study was to evaluate the antioxidant activity of crude extract and chloroform, ethyl acetate and n-butanol fractions from its leaves, verifying the ability to remove reactive species and identify and quantify phenolic compounds. The ethyl acetate fraction showed the highest amount of total polyphenols (546.57 ± 2.35 mg gallic acid equivalent/g) and the lowest IC50 (9.11 ± 0.75 µg/mL) by the DPPH method. Furthermore, the chloroform fraction presented the highest content of flavonoids (75.73 ± 0.34 mg rutin equivalents/g), tannins (56.03 ± 0.68 mg catechin equivalents/g) and alkaloids (10.79 ± 0.06 mg/g). This fraction was effective in the scavenging of reactive species by 2′,7′-dichlorofluorescein diacetate assay, in addition to completely reducing protein carbonyl content and reducing lipid peroxidation at basal levels even at low concentrations. Chlorogenic, caffeic and rosmarinic acids were identified and quantified by HPLC/DAD. These results show that S. guaraniticum is rich in phenolic compounds and has potential as an antioxidant.

Response of oxidative stress and inflammatory biomarkers to a 12-week aerobic exercise training in women with metabolic syndrome

BackgroundEvidences have been highlighted the relationship among metabolic syndrome, chronic low-grade inflammation, oxidative stress and several diseases. In this sense, the aim of this study was to investigate the effects of aerobic exercise training on oxidative stress and inflammatory parameters on women with metabolic syndrome (MS).MethodsTwenty-three untrained women (51.86 ± 6.58 years old, BMI 30.8 ± 4.3 kg/m2) completed a 12-week treadmill exercise training, without modifications on dietary pattern. Advanced oxidation protein products (AOPP), thiobarbituric acid-reactive substances (TBARS), total thiol content (T-SH) and nitrite and nitrate (NOx) levels were assessed in plasma while the levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-α) and interferon-gamma (IFN-γ) were evaluated in the serum. The RNA expression (mRNA) of IL-1β, IL-10, TNF-α, IFN-γ, insulin receptor substrate 2 (IRS-2) and matrix metalloproteinase-9 (MMP-9) were performed inperipheral blood mononuclear cells (PBMC) of a subset with eight women with MS using real real-time polymerase chain reaction (qPCR).ResultsThe intervention resulted in decreased serum levels of IL-1β, IL-6, TNF-α, IFN-γ, AOPP and TBARS, besides increased levels of IL-10 and T-SH (P < 0.001). NOx concentrations were unchanged, similarly to mRNA expressions quantified in PBMC.ConclusionsTwelve weeks of AT improved systemic oxidative stress and inflammatory biomarkers in women with MS, although PBMC mRNA expression for inflammatory pathways appeared to be unchanged. This may indicate that AT induced beneficial effects not only in physical fitness but also on health promotion through decreased oxidative damage and proinflammatory status.

Antioxidant activity of β-selenoamines and their capacity to mimic different enzymes

The antioxidant properties of organoselenium compounds have been extensively investigated because oxidative stress is a hallmark of a variety of chronic human diseases. Here, we reported the influence of substituent groups in the antioxidant activity of β-selenoamines. We have investigated whether they exhibited glutathione peroxidase-like (GPx-like) activity and whether they could be substrate of thioredoxin reductase (TrxR). In the DPPH assay, the β-selenium amines did not exhibit antioxidant activity. However, the β-selenium amines with p-methoxy and tosyl groups prevented the lipid peroxidation. The β-selenium amine compound with p-methoxy substituent group exhibited thiol-peroxidase-like activity (GPx-like activity) and was reduced by the hepatic TrxR. These results contribute to understand the influence of structural alteration of non-conventional selenium compounds as synthetic mimetic of antioxidant enzymes of mammalian organisms.

Caffeine supplementation modulates oxidative stress markers in the liver of trained rats

AIMS Caffeine has been widely used in sports competitions due to its ergogenic effects. Most of the studies regarding caffeine and exercise have focused on muscle and plasma adaptations, while the impact on the liver is scarcely described. The aim is to analyze the effects of caffeine and exercise training on oxidative stress markers and injury-related parameters in the liver. MAIN METHODS Rats were divided into sedentary/saline, sedentary/caffeine, exercise/saline, and exercise/caffeine groups. Exercise groups underwent 4 weeks of swimming training, and caffeine (6 mg/kg, p.o.) was supplemented throughout the training protocol. Injury-related liver parameters were assessed in plasma, while redox status and oxidative stress markers were measured on liver homogenates. KEY FINDINGS Exercise training increased muscle citrate synthase activity in the muscle, while in caffeine decreased its activity in both sedentary and trained rats. Aspartate transaminase levels were increased after training, and caffeine intake suppressed this elevation (p<0.05). Caffeine also diminished alanine transaminase levels in both sedentary and exercised rats (p<0.05). Exercise training induced a significant increase on the activity of the enzymes superoxide dismutase and glutathione peroxidase, as an increase on thiobarbituric acid-reactive substances levels was also reached (p<0.05); caffeine intake blunted these alterations. Caffeine intake also suppressed liver catalase activity in both sedentary and exercise groups (p<0.05). SIGNIFICANCE Our data suggest that caffeine modified the hepatic responses associated to exercise-induced oxidative stress without affecting the performance, exerting different actions according to the tissue. However, further studies are needed to better understand caffeines role on liver under exercise training.

In vitro antioxidant activity of stem bark of Trichilia catigua Adr. Juss

Antioxidant activity of the ethanolic extract and fractions from the stem bark of T. catigua was investigated. IC50 (for DPPH scavenging) by T. catigua varied from 9.17 ± 0.63 to 76.42 ± 5.87 mg mL-1 and total phenolic content varied from 345.63 ± 41.08 to 601.27 ± 42.59 mg GAE g-1 of dry extract. Fe2+-induced lipid peroxidation was significantly reduced by the ethanolic extract and fractions. Mitochondrial Ca2+-induced dichlorofluorescein oxidation was significantly reduced by the ethanolic extract in a concentration-dependent manner. Ethanolic extract reduced mitochondrial Dym only at high concentrations (40-100 mg mL-1), which indicates that its toxicity does not overlap with its antioxidant effects. Results suggest involvement of antioxidant activities of T. catigua in its pharmacological properties. U radu je opisano ispitivanje antioksidativnog u~inka etanolnog ekstrakta i pojedinih frakcija kore stabljike T. catigua. IC50 (za DPPH test) varirao je izme|u 9,17 ± 0,63 i 76,42 ± 5,87 mg mL-1, a ukupni sadr`aj fenola od 345,63 ± 41,08 i 601,27 ± 42,59 mg GAE po gramu suhog ekstrakta. Etanolni ekstrakt i frakcije zna~ajno su reducirale Fe2+-induciranu lipidnu peroksidaciju. Nadalje, reducirana je oksidacija diklorfluoresceina inducirana ionima kalcija u mitohondrijima, a redukcija je ovisila o dozi etanolnog ekstrakta. Etanolni ekstrakt smanjio je mitohondrijsku Dym samo pri visokim koncentracijama (40 ± 100 mg mL-1), {to ukazuje da se toksi~nost ne preklapa s antioksidativnim u~inkom. Rezultati pokazuju da u farmakolo{ko djelovanje T. catigua treba uklju~iti i antioksidativni u~inak.

Caffeine Intake May Modulate Inflammation Markers in Trained Rats

Caffeine is presented in many commercial products and has been proven to induce ergogenic effects in exercise, mainly related to redox status homeostasis, inflammation and oxidative stress-related adaptation mechanisms. However, most studies have mainly focused on muscle adaptations, and the role of caffeine in different tissues during exercise training has not been fully described. The aim of this study was therefore, to analyze the effects of chronic caffeine intake and exercise training on liver mitochondria functioning and plasma inflammation markers. Rats were divided into control, control/caffeine, exercise, and exercise/caffeine groups. Exercise groups underwent four weeks of swimming training and caffeine groups were supplemented with 6 mg/kg/day. Liver mitochondrial swelling and complex I activity, and plasma myeloperoxidase (MPO) and acetylcholinesterase (AChE) activities were measured. An anti-inflammatory effect of exercise was evidenced by reduced plasma MPO activity. Additionally, caffeine intake alone and combined with exercise decreased the plasma AChE and MPO activities. The per se anti-inflammatory effect of caffeine intake should be highlighted considering its widespread use as an ergogenic aid. Therefore, caffeine seems to interfere on exercise-induced adaptations and could also be used in different exercise-related health treatments.

Effect of diselenide administration in thioacetamide-induced acute neurological and hepatic failure in mice

Hepatic encephalopathy is a common complication of severe acute hepatic failure and has been associated with high short-term mortality rates. Therefore, the aim of this study was to investigate the effect of diphenyl diselenide (DPDS) and its analogues in protecting against thioacetamide (TAA)-induced acute neurological and hepatic failure in mice. The animals received a TAA dose of 200 mg kg−1 intraperitoneally, and then, 1 hour later, they received 15.6 mg kg−1 of diselenides intraperitoneally. Twenty three hours after diselenide administration, the animals were sacrificed, and blood, brain and liver samples were collected for analysis. The results showed that mice exposed to TAA presented oxidative stress characteristics, such as an increase in lipid peroxidation (LPO), enhanced glutathione peroxidase activity and a decrease in the GSH/GSSH ratio in the brain and liver. In addition, the TAA group showed a decrease in cellular viability in both tissues. TAA treatments also generate reactive oxygen species and cause inhibition of glutathione-S-transferase in liver, which were associated with TAA exacerbated half-life in this tissue. In the histopathological analyses, we observed that TAA induced a large inflammation process that was confirmed according to the elevation of liver myeloperoxidase activity. Moreover, the treatment with diselenides reduced the oxidative stress significantly. Additionally, after the establishment of acute hepatic failure (AHF), DPDS was able to inhibit the inflammatory processes with a more significant decrease in major hepatic damage effects than was presented after treatment with its analogues. Thus, our results showed that DPDS is a promising therapeutic option for the treatment of AHF and hepatic encephalopathy as mice returned to normal conditions after the damage.

Centella asiatica and Its Fractions Reduces Lipid Peroxidation Induced by Quinolinic Acid and Sodium Nitroprusside in Rat Brain Regions.

Oxidative stress has been implicated in several pathologies including neurological disorders. Centella asiatica is a popular medicinal plant which has long been used to treat neurological disturbances in Ayurvedic medicine. In the present study, we quantified of compounds by high performance liquid chromatography (HPLC) and examined the phenolic content of infusion, ethyl acetate, n-butanolic and dichloromethane fractions. Furthermore, we analyzed the ability of the extracts from C. asiatica to scavenge the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) radical as well as total antioxidant activity through the reduction of molybdenum (VI) (Mo6+) to molybdenum (V) (Mo5+). Finally, we examined the antioxidant effect of extracts against oxidant agents, quinolinic acid (QA) and sodium nitroprusside (SNP), on homogenates of different brain regions (cerebral cortex, striatum and hippocampus). The HPLC analysis revealed that flavonoids, triterpene glycoside, tannins, phenolic acids were present in the extracts of C. asiatica and also the phenolic content assay demonstrated that ethyl acetate fraction is rich in these compounds. Besides, the ethyl acetate fraction presented the highest antioxidant effect by decreasing the lipid peroxidation in brain regions induced by QA. On the other hand, when the pro-oxidant agent was SNP, the potency of infusion, ethyl acetate and dichloromethane fractions was equivalent. Ethyl acetate fraction from C. asiatica also protected against thiol oxidation induced by SNP and QA. Thus, the therapeutic potential of C. asiatica in neurological diseases could be associated to its antioxidant activity.

Synthesis, Structure Elucidation, Antioxidant and Antimicrobial Activity of Novel 2-(5-Trifluoromethyl-1H-pyrazol-1-yl)-5-(5-trihalomethyl-1H-pyrazol-1-yl-1- carbonyl)pyridines

This paper describes an efficient approach for the synthesis of a novel series of sixteen 2-(5-trifluoromethyl-1H-pyrazol-1-yl)-5-(5-trihalomethyl-1H-pyrazol-1-yl-1-carbonyl) pyridines, for the first time with non-identical substituents in both pyrazole rings, through the cyclocondensation reaction of 4-methoxy-4-alkyl(aryl/heteroaryl-1,1,1-trihaloalk-3-en-2-ones [CX3C(O)CH=CR1OCH3, in which R1 = CH3, C6H5, 4-CH3C6H4, 4-OCH3C6H4, 2-furyl and X = F, Cl] or acetylacetone with some 6-[3-alkyl(aryl)-5-trifluoromethyl-1H-pyrazol-1-yl]nicotinohydrazides. Optimized yields of 67-91% were obtained when the reactions were performed in ethanol (green solvent) at reflux for 16 h. Subsequent antioxidant and antimicrobial evaluation revealed promising 1,1-diphenyl-2-picrylhydrazyl (DPPH) inhibition percentage and exhibited fungiostatic and fungicidal activities against yeasts, dermatophytes and filamentous, especially for the pyridine systems, when the both pyrazole rings attached to a pyridine ring contain CX3 groups (X = H, F, Cl) of different kinds. It is also observed the trichloromethyl substituted compounds presented higher antioxidant activity in comparison to their fluorinated analogous.