Gut microbiota, diet, and chronic diseases: the role played by oxidative stress

The authors gratefully acknowledge the Espirito Santo Research Foundation (FAPES) (Grant CNPq/FAPES No. 24/2018; Termo Outorga 569/2018) and the Brazilian National Council for Research and Development (CNPq) (CNPq Grant Bolsa Produtividade 2015-2019) for the financial support to our research projectS

Extreme blood lactate rising after very short efforts in top-level track and field male sprinters

Two top-level (10”04 and 10”13 in 100-m dash) and 2 sub-elite (10”97 and 11”44 in 100-m dash) male sprinters completed, after a standardised warm-up, various jump, sprint and weightlifting exercises in two consecutive days at the start of pre-season. Before and 30 s after the tests, the [La−] were measured with a portable lactate analyser. The top-level sprinters exhibited much larger [La−] than the sub-elite sprinters (< 5 mmol·L-1) after all the exercise tests. The maximum values recorded were 20.4 mmol·L-1 after the 20-m sprint tests for Athlete 1, and 22.4 mmol·L-1 after CMJ testing for Athlete 2. The greater Δ% were recorded after CMJ testing for Athlete 1 (from 1.9 to 13.6 mmol·L-1), and after the power clean test for Athlete 2 (from 1.4 to 17.6 mmol·L-1). These results suggest a different metabolic response to very short efforts (≤3 s) in top-level track and field sprinters. These findings reinforce the need to include lactate assessments, during training and evaluation sessions, to better understand the acute and chronic adaptations to training of sprinters of different levels

Nanomolar resveratrol reduces early alterations of pancreatitis and pancreatic cancer in pancreatic acinar cells

Resveratrol is a natural phytoalexin present in human diet with a potential beneficial effect in many diseases including chronic and acute pancreatitis, a potentially fatal disease with significant morbimortality accompanied with obscure pathogenesis and without effective treatments. Resveratrol has also been shown to be a promising anti-tumor molecule on the millimolar scale. In this study, the protective effects of nanomolar concentrations of resveratrol against early events common to pancreatic cancer and pancreatitis induced by supra-physiological concentrations of cholecystokinin (CCK, 100 nM) were evaluated. Resveratrol (200, 500 nM) reduced CCK-induced intracellular trypsin activation and cell injury in isolated rat pancreatic acinar cells (PAC). The damage induced by high CCK and the protective effect of resveratrol was also measured in pancreatic tissue explants by analyzing histological changes. Finally, the effect of resveratrol on the CCK-enhanced nuclear factor κB (NF-κB) expression was studied by Western blot experiments in the AR42J pancreatic acinar cell line. Our results show, for the first time, the ability of resveratrol to reduce premature intracellular activation of trypsin and necrosis in PAC. It is suggested that resveratrol counteracts CCK-induced pancreatic tissue breakdown by downregulation of NF-κB in the nuclear fraction. Since these effects occur at nanomolar concentrations that can be achieved by oral intake, our results suggest that dietary consumption of resveratrol could have a preventive effect and delay the evolution of pancreatitis and pancreatic cancer.</p

Nanomolar resveratrol reduces early alterations of pancreatitis and pancreatic cancer in pancreatic acinar cells

Resveratrol is a natural phytoalexin present in human diet with a potential beneficial effect in many diseases including chronic and acute pancreatitis, a potentially fatal disease with significant morbimortality accompanied with obscure pathogenesis and without effective treatments. Resveratrol has also been shown to be a promising anti-tumor molecule on the millimolar scale. In this study, the protective effects of nanomolar concentrations of resveratrol against early events common to pancreatic cancer and pancreatitis induced by supra-physiological concentrations of cholecystokinin (CCK, 100 nM) were evaluated. Resveratrol (200, 500 nM) reduced CCK-induced intracellular trypsin activation and cell injury in isolated rat pancreatic acinar cells (PAC). The damage induced by high CCK and the protective effect of resveratrol was also measured in pancreatic tissue explants by analyzing histological changes. Finally, the effect of resveratrol on the CCK-enhanced nuclear factor κB (NF-κB) expression was studied by Western blot experiments in the AR42J pancreatic acinar cell line. Our results show, for the first time, the ability of resveratrol to reduce premature intracellular activation of trypsin and necrosis in PAC. It is suggested that resveratrol counteracts CCK-induced pancreatic tissue breakdown by downregulation of NF-κB in the nuclear fraction. Since these effects occur at nanomolar concentrations that can be achieved by oral intake, our results suggest that dietary consumption of resveratrol could have a preventive effect and delay the evolution of pancreatitis and pancreatic cancer

Sildenafil (Viagra®) Prevents Cox-1/ TXA2 Pathway-Mediated Vascular Hypercontractility in ApoE-/- Mice

Background/Aims: The atherosclerotic apolipoprotein E-deficient (apoE-/-) mouse exhibits impaired vasodilation and enhanced vasoconstriction responsiveness. The objectives of this study were: a) to determine the relative contribution of cyclooxygenases (Cox-1 and Cox-2), thromboxane A2 (TXA2) and endothelin-1 (ET-1) to enhancing vascular hyperresponsiveness in this model of atherosclerosis and b) to investigate the beneficial effects of the phosphodiesterase 5 inhibitor sildenafil on this endothelial dysfunction. Methods: Adult male apoE-/- mice were treated with sildenafil (40 mg/kg/day, for 3 weeks) and compared with non-treated ApoE-/- and wild-type mice. The beneficial effects of sildenafil on vascular contractile response to phenylephrine (PE) in aortic rings were evaluated before and after incubation with Cox-1 (SC-560) or Cox-2 (NS-398) inhibitors or the TP antagonist SQ-29548, and on contractile responsiveness to ET-1. Results: ApoE-/- mice exhibited enhanced vasoconstriction to PE (Rmax ∼35%, p&#x3c;0.01), which was prevented by treatment with sildenafil. The enhanced PE-induced contractions were abolished by both Cox-1 inhibition and TP antagonist, but were not modified by Cox-2 inhibition. Aortic rings from ApoE-/- mice also exhibited enhanced contractions to ET-1 (Rmax ∼30%, p&#x3c;0.01), which were attenuated in sildenafil-treated ApoE-/- mice. In addition, we observed augmented levels of vascular proinflammatory cytokines in ApoE-/- mice, which were partially corrected by treatment with sildenafil (IL-6, IL-10/IL-6 ratio and MCP-1). Conclusion: The present data show that the Cox-1/TXA2 pathway prevails over the Cox-2 isoform in the mediation of vascular hypercontractility observed in apoE-/-mice. The results also show a beneficial effect of sildenafil on this endothelial dysfunction and on the proinflammatory cytokines in atherosclerotic animals, opening new perspectives for the treatment of other endothelium-related cardiovascular abnormalities

Atividade do sistema antioxidante e desenvolvimento de aerênquima em raízes de milho 'Saracura' Antioxidant system activity and aerenchyma formation in 'Saracura' maize roots

Este trabalho teve como objetivo avaliar a influência de sucessivos ciclos de seleção do milho 'Saracura' na atividade das enzimas do sistema antioxidante, e a relação dessas enzimas com a capacidade dessa variedade em desenvolver aerênquima. Sementes de 18 ciclos de seleção intercalados do milho 'Saracura' e da cultivar BR 107, sensível à hipoxia, foram semeadas em vasos e em casa de vegetação. As plantas foram submetidas ao alagamento intermitente de dois em dois dias. As amostras de raízes foram coletadas após 60 dias e analisaram-se as atividades das enzimas peroxidase do guaiacol, peroxidase do ascorbato e catalase, além da capacidade das plantas de cada ciclo desenvolverem aerênquima. Ao longo dos ciclos, as plantas apresentaram modificações na atividade das enzimas, com aumento na de peroxidase do ascorbato e diminuição na de catalase e de peroxidase do guaiacol. Observou-se, ainda, maior capacidade de desenvolver aerênquima nos últimos ciclos de seleção. A redução na atividade das enzimas do sistema antioxidante parece estar relacionada a um desbalanço na decomposição de H2O2.<br>This work aimed to assess the influence of successive selection cycles in 'Saracura' maize on the enzyme activity of the antioxidant system and the relationship of these enzymes with the aerenchyma development capacity of this variety. Seeds of 18 intercalated selection cycles of the 'Saracura' maize and of the cultivar BR 107, sensitive to hipoxia, were sown in pots in the greenhouse. Plants were submitted to intermittent soil flooding each two days. After 60 days, the roots were sampled and analysis were done for the guaiacol peroxidase, ascorbate peroxidase, and catalase activities and for the capacity of the plants of each cycle to develop aerenchyma. The plants showed modifications in enzyme activity along the cycles, increasing the ascorbate peroxidase activity and decreasing the catalase and guaiacol peroxidase ones. A greater capacity to develop aerenchyma was also observed in the last selection cycles. Reductions in the enzyme activity of the antioxidant system seem to be related to a disorder in the H2O2 decomposition capacity