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1.
Biomolecules ; 9(7)2019 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-31284470

RESUMO

It is well known that biological systems, such as microorganisms, plants, and animals, including human beings, form spontaneous electronically excited species through oxidative metabolic processes. Though the mechanism responsible for the formation of electronically excited species is still not clearly understood, several lines of evidence suggest that reactive oxygen species (ROS) are involved in the formation of electronically excited species. This review attempts to describe the role of ROS in the formation of electronically excited species during oxidative metabolic processes. Briefly, the oxidation of biomolecules, such as lipids, proteins, and nucleic acids by ROS initiates a cascade of reactions that leads to the formation of triplet excited carbonyls formed by the decomposition of cyclic (1,2-dioxetane) and linear (tetroxide) high-energy intermediates. When chromophores are in proximity to triplet excited carbonyls, the triplet-singlet and triplet-triplet energy transfers from triplet excited carbonyls to chromophores result in the formation of singlet and triplet excited chromophores, respectively. Alternatively, when molecular oxygen is present, the triplet-singlet energy transfer from triplet excited carbonyls to molecular oxygen initiates the formation of singlet oxygen. Understanding the mechanism of the formation of electronically excited species allows us to use electronically excited species as a marker for oxidative metabolic processes in cells.


Assuntos
Espécies Reativas de Oxigênio/metabolismo , Animais , Transferência de Energia , Humanos , Oxirredução , Oxigênio/metabolismo
2.
Vnitr Lek ; 64(7-8): 735-741, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30441981

RESUMO

Obesity reaches the dimensions of the global epidemic. It directly contributes to an increase in the prevalence of systemic diseases associated with obesity. Obesity and overweight globally cause 3.5 million deaths annually [1]. Non-alcoholic fatty liver disease has become the most common chronic liver disease in developed countries and is considered to be a liver manifestation of metabolic syndrome. The extent and burden of the disease are increasing and reaching epidemic proportions because of its close association with the epidemic of obesity and diabetes mellitus type [2]. It affects 30 % of the adult population [2]. There is an alarming increase in prevalence among children and adolescents. However, in the group of patients with high cardiometabolic risk, we can see a significantly higher prevalence of NAFLD. Prevalence in obese patients is 75 -92 %, in diabetic patients prevalence is between 60 -70 % [3]. A significant proportion of patients with NAFLD will suffer from a progressive form of the disease - non-alcoholic steatohepatitis (NASH), which is associated with the development of advanced liver fibrosis, cirrhosis, and its complications. The growing prevalence of NASH in the near future will bring the advanced cohort of our patients to the stage of an advanced liver disease. If the adverse epidemiological trend is not reversed, in the next decade the most common cause of liver transplantation will be NASH. A steadily rising trend can be seen in an increase in the number of cases of hepatocellular carcinoma causally related to NASH [4]. Treatment based on the influence of key pathogenetic mechanisms could alter the individual's future as well as the global burden arising with NASH. New molecules with anti-inflammatory and antifibrotic effects will play a key role in the future. Key words: cirrhosis - insulin resistance - metabolic syndrome - NASH.


Assuntos
Cirrose Hepática , Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Adolescente , Adulto , Criança , Humanos , Cirrose Hepática/complicações , Síndrome Metabólica/complicações , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Obesidade
3.
Can J Gastroenterol Hepatol ; 2018: 6095097, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30402450

RESUMO

Background and Aims: Chronic hepatitis C is a systemic disease and type 2 diabetes mellitus (T2DM) belongs to more common extrahepatic. The aim of this study was to (i) explore the prevalence of impaired fasting glucose (IFG) and T2DM in patients with chronic hepatitis C, (ii) explore the effect of direct acting antivirals (DAA) treatment on the glycemia, and (iii) explore the factors that modulate the effect of DAA treatment on glycemia in patients with chronic hepatitis C. Methods: We performed a longitudinal retrospective observational study focused on the patients undergoing DAA treatment of chronic hepatitis C. Data about glycemia, history of diabetes, hepatitis C virus, treatment, and liver status, including elastography, were obtained at baseline (before treatment start), at the end of treatment and 12 weeks after the end of treatment. Patients were treated with various regimens of direct acting antivirals. Results: We included 370 patients; 45.9% had F4 fibrosis. At baseline, the prevalence of T2DM increased with the degree of fibrosis (F0-F2 14.4%, F3 21.3%, and F4 31.8%, p=0.004). Fasting glycemia also increased with the degree of fibrosis (F0-F2 5.75±0.18 F3 5.84±0.17, and F4 6.69±0.2 mmol/L, p=0.001). We saw significant decrease of glycemia after treatment in all patients, but patients without T2DM or IFG from 6.21±0.12 to 6.08±0.15 mmol/L (p=0.002). The decrease was also visible in treatment experienced patients and patients with Child-Pugh A cirrhosis. Conclusion: We confirmed that the prevalence of either T2DM or IFG increases in chronic hepatitis C patients with the degree of fibrosis. The predictive factors for T2DM were, besides F4, fibrosis also higher age and BMI. Significant decrease of fasting glycemia after the DAA treatment was observed in the whole cohort and in subgroups of patients with T2DM, IFG, cirrhotic, and treatment experienced patients.


Assuntos
Antivirais/uso terapêutico , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/epidemiologia , Intolerância à Glucose/epidemiologia , Hepatite C Crônica/sangue , Fatores Etários , Glicemia/efeitos dos fármacos , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etiologia , Jejum/sangue , Feminino , Intolerância à Glucose/sangue , Intolerância à Glucose/etiologia , Hepacivirus , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Fígado/patologia , Cirrose Hepática/sangue , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
4.
Plant J ; 2018 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-29901834

RESUMO

Prenylquinols (tocochromanols and plastoquinols) serve as efficient physical and chemical quenchers of singlet oxygen (1 O2 ) formed during high light stress in higher plants. Although quenching of 1 O2 by prenylquinols has been previously studied, direct evidence for chemical quenching of 1 O2 by plastoquinols and their oxidation products is limited in vivo. In the present study, the role of plastoquinol-9 (PQH2 -9) in chemical quenching of 1 O2 was studied in Arabidopsis thaliana lines overexpressing the SOLANESYL DIPHOSPHATE SYNTHASE 1 gene (SPS1oex) involved in PQH2 -9 and plastochromanol-8 biosynthesis. In this work, direct evidence for chemical quenching of 1 O2 by plastoquinols and their oxidation products is presented, which is obtained by microscopic techniques in vivo. Chemical quenching of 1 O2 was associated with consumption of PQH2 -9 and formation of its various oxidized forms. Oxidation of PQH2 -9 by 1 O2 leads to plastoquinone-9 (PQ-9), which is subsequently oxidized to hydroxyplastoquinone-9 [PQ(OH)-9]. We provide here evidence that oxidation of PQ(OH)-9 by 1 O2 results in the formation of trihydroxyplastoquinone-9 [PQ(OH)3 -9]. It is concluded here that PQH2 -9 serves as an efficient 1 O2 chemical quencher in Arabidopsis, and PQ(OH)3 -9 can be considered as a natural product of 1 O2 reaction with PQ(OH)-9. The understanding of the mechanisms underlying 1 O2 chemical quenching provides information on the role of plastoquinols and their oxidation products in the response of plants to photooxidative stress.

5.
Eur J Gastroenterol Hepatol ; 27(4): 405-11, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25874513

RESUMO

BACKGROUND: Multiple studies have recently proposed the lowering of upper limit of normal (ULN) for alanine aminotransferase (ALT) to improve the diagnostic sensitivity for viral hepatitides and metabolic syndrome (MS). We have tried to validate some of the proposed ULNs in the diagnosis of MS. METHODS: We used data from the HepaMeta Study conducted in 2011 in Slovakia, which explored the prevalence of MS in eastern Slovakia. Patients were tested for the criteria of MS and ALT. Different, previously published, ALT cutoffs were then used to calculate odds' ratios, sensitivity, specificity, and accuracy of MS and its components. RESULTS: Manufacturers' recommended ULN used in our institution (0.8 µkat/l, 47 U/l for men and 0.6 µkat/l, 35 U/l for women) failed to predict any significant risk of MS. Lowered cutoff (72% of the original ULN) identified the patients with the highest age-adjusted probability of MS (odds ratio 3.194, 95% confidence interval 1.398-7.295). ALT was significantly associated with elevated levels of triacylglycerols, hyperglycemia, and obesity. CONCLUSION: In patients with MS, one must consider liver involvement if the patient has ALT levels in the upper third of the reference range. There is the need for discussion about the feasibility of lower ALT ULN in clinical practice.


Assuntos
Alanina Transaminase/sangue , Síndrome Metabólica/diagnóstico , Adulto , Idoso , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/enzimologia , Pessoa de Meia-Idade , Razão de Chances , Padrões de Referência , Medição de Risco , Sensibilidade e Especificidade
6.
PLoS One ; 10(3): e0116958, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25730422

RESUMO

The exposure of human cells to oxidative stress leads to the oxidation of biomolecules such as lipids, proteins and nuclei acids. In this study, the oxidation of lipids, proteins and DNA was studied after the addition of hydrogen peroxide and Fenton reagent to cell suspension containing human leukemic monocyte lymphoma cell line U937. EPR spin-trapping data showed that the addition of hydrogen peroxide to the cell suspension formed hydroxyl radical via Fenton reaction mediated by endogenous metals. The malondialdehyde HPLC analysis showed no lipid peroxidation after the addition of hydrogen peroxide, whereas the Fenton reagent caused significant lipid peroxidation. The formation of protein carbonyls monitored by dot blot immunoassay and the DNA fragmentation measured by comet assay occurred after the addition of both hydrogen peroxide and Fenton reagent. Oxidative damage of biomolecules leads to the formation of singlet oxygen as conformed by EPR spin-trapping spectroscopy and the green fluorescence of singlet oxygen sensor green detected by confocal laser scanning microscopy. It is proposed here that singlet oxygen is formed by the decomposition of high-energy intermediates such as dioxetane or tetroxide formed by oxidative damage of biomolecules.


Assuntos
Radical Hidroxila/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Oxigênio Singlete/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Ensaio Cometa , Espectroscopia de Ressonância de Spin Eletrônica , Humanos , Peróxido de Hidrogênio/toxicidade , Ferro/toxicidade , Leucemia/metabolismo , Leucemia/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/análise , Microscopia Confocal , Carbonilação Proteica/efeitos dos fármacos
7.
Sci Rep ; 5: 8882, 2015 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-25744165

RESUMO

In this study, evidence is provided on the formation of electronically excited species in human multiple myeloma cells U266 in the growth medium exposed to hydrogen peroxide (H2O2). Two-dimensional imaging of ultra-weak photon emission using highly sensitive charge coupled device camera revealed that the addition of H2O2 to cell suspension caused the formation of triplet excited carbonyls (3)(R = O)*. The kinetics of (3)(R = O)* formation in the real time, as measured by one-dimensional ultra-weak photon emission using low-noise photomultiplier, showed immediate enhancement followed by a slow decay. In parallel to the formation of (3)(R = O)*, the formation of singlet oxygen ((1)O2) in U266 cells caused by the addition of H2O2 was visualized by the imaging of (1)O2 using the green fluorescence of singlet oxygen sensor green detected by confocal laser scanning microscopy. Additionally, the formation of (1)O2 after the addition of H2O2 to cell suspension was detected by electron paramagnetic resonance spin-trapping spectroscopy using 2,2,6,6-tetramethyl-4-piperidone. Presented results indicate that the addition of H2O2 to cell suspension results in the formation of (3)(R = O)* and (1)O2 in U266 cell suspension. The contribution of the cell-free medium to the formation of electronically excited species was discussed.


Assuntos
Fenômenos Eletrofisiológicos , Peróxido de Hidrogênio/metabolismo , Mieloma Múltiplo/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Espectroscopia de Ressonância de Spin Eletrônica , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/farmacologia , Microscopia Confocal , Espécies Reativas de Oxigênio/metabolismo , Células Tumorais Cultivadas
8.
J Photochem Photobiol B ; 139: 11-23, 2014 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-24674863

RESUMO

Ultra-weak photon emission originates from the relaxation of electronically excited species formed in the biological systems such as microorganisms, plants and animals including humans. Electronically excited species are formed during the oxidative metabolic processes and the oxidative stress reactions that are associated with the production of reactive oxygen species (ROS). The review attempts to overview experimental evidence on the involvement of superoxide anion radical, hydrogen peroxide, hydroxyl radical and singlet oxygen in both the spontaneous and the stress-induced ultra-weak photon emission. The oxidation of biomolecules comprising either the hydrogen abstraction by superoxide anion and hydroxyl radicals or the cycloaddition of singlet oxygen initiate a cascade of oxidative reactions that lead to the formation of electronically excited species such as triplet excited carbonyl, excited pigments and singlet oxygen. The photon emission of these electronically excited species is in the following regions of the spectrum (1) triplet excited carbonyl in the near UVA and blue-green areas (350-550nm), (2) singlet and triplet excited pigments in the green-red (550-750nm) and red-near IR (750-1000nm) areas, respectively and (3) singlet oxygen in the red (634 and 703nm) and near IR (1270nm) areas. The understanding of the role of ROS in photon emission allows us to use the spontaneous and stress-induced ultra-weak photon emission as a non-invasive tool for monitoring of the oxidative metabolic processes and the oxidative stress reactions in biological systems in vivo, respectively.


Assuntos
Fotobiologia/métodos , Fótons , Espécies Reativas de Oxigênio/metabolismo , Animais , Elétrons , Humanos , Oxirredução
9.
J Bioenerg Biomembr ; 45(6): 551-9, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23934145

RESUMO

In this study, electron paramagnetic resonance spin-trapping spectroscopy was used to study the light-induced production of superoxide anion (O2 (•-)) and carbon-centered (R(•)) radicals by Photosystem II (PSII). It is evidenced here that exposure of PSII membranes to high light (2,000 µmol photons m(-2) s(-1)) or heat (47 °C) treatments prior to the illumination suppressed O2 (•-) production, while R(•) was formed. Formation of R(•) in the both high light- and heat-treated PSII membranes was enhanced by DCMU. Removal of molecular oxygen by glucose/glucose oxidase/catalase system and O2 (•-) scavenging by exogenous superoxide dismutase completely suppressed carbon-centered radical formation. It is proposed here that the oxidation of polyunsaturated fatty acids and amino acids by O2 (•-) on the electron acceptor side of PSII results in the formation of R(•), known to initiate a cascade reaction leading to the lipid peroxidation and protein degradation, respectively.


Assuntos
Radicais Livres/metabolismo , Oxigênio/metabolismo , Complexo de Proteína do Fotossistema II/metabolismo , Detecção de Spin/métodos , Superóxidos/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Radicais Livres/química , Luz , Oxirredução , Oxigênio/química , Processos Fotoquímicos , Complexo de Proteína do Fotossistema II/química , Spinacia oleracea , Superóxidos/química
10.
Curr Control Trials Cardiovasc Med ; 6(1): 4, 2005 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-15790413

RESUMO

BACKGROUND: Activation of inflammatory pathways plays an important contributory role in coronary plaque instability and subsequent rupture, which can lead to the development of acute coronary syndrome (ACS). Elevated levels of serum inflammatory markers such as C-reactive protein (CRP) represent independent risk factors for further cardiovascular events. Recent evidence indicates that in addition to lowering cholesterol levels, statins also decrease levels of inflammatory markers. Previous controlled clinical trials reporting the positive effects of statins in participants with ACS were designed for very early secondary prevention. To our knowledge, no controlled trials have evaluated the potential benefits of statin therapy, beginning immediately at the time of hospital admission. A previous pilot study performed by our group focused on early initiation of cerivastatin therapy. We demonstrated a highly significant reduction in levels of inflammatory markers (CRP and interleukin-6). Based on these preliminary findings, we are conducting a clinical trial to evaluate the efficacy of another statin, fluvastatin, as an early intervention in patients with ACS. METHODS: The FACS-trial (Fluvastatin in the therapy of Acute Coronary Syndrome) is a multicenter, randomized, double-blind, placebo-controlled study evaluating the effects of fluvastatin therapy initiated at the time of hospital admission. The study will enroll 1,000 participants admitted to hospital for ACS (both with and without ST elevation). The primary endpoint for the study is the influence of fluvastatin therapy on levels of inflammatory markers (CRP and interleukin-6) and on pregnancy associated plasma protein A (PAPP-A). A combined secondary endpoint is 30-day and one-year occurrence of death, nonfatal myocardial infarction, recurrent symptomatic ischemia, urgent revascularization, and cardiac arrest. CONCLUSION: The primary objective of the FACS trial is to demonstrate that statin therapy, when started immediately after hospital admission for ACS, results in reduction of inflammation and improvement of prognosis. This study may contribute to new knowledge regarding therapeutic strategies for patients suffering from ACS and may offer additional clinical indications for the use of statins.

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