Assuntos
Antineoplásicos/efeitos adversos , Carcinoma de Células Escamosas/terapia , Cisplatino/efeitos adversos , Neoplasias de Cabeça e Pescoço/terapia , Peróxidos Lipídicos/urina , Malondialdeído/urina , Nitritos/urina , Estresse Oxidativo/efeitos dos fármacos , Radioterapia/métodos , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Biomarcadores/urina , Carcinoma de Células Escamosas/urina , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Neoplasias de Cabeça e Pescoço/urina , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos da radiação , Estudos ProspectivosRESUMO
UNLABELLED: Oxidative stress caused by increased production of free radicals and impaired functions of antioxidants remains as the major factor associated with the pathophysiology of many neuropsychiatric diseases. OBJECTIVE: The objective of the present study was to analyze the oxidative stress markers in urine sample since the collection of blood from these children is highly meticulous and also to evaluate whether these urinary markers can be correlated with the severity of autism. METHODS: The subjects of the study were 45 autistic children with different grades of severity (low functioning autism (LFA), medium functioning autism (MFA), and high functioning autism (HFA) according to Childhood Autism Rating Scale (CARS), n=15 children in each group and 50 healthy children (age and sex matched). The boys and girls ratio involved in this study was 4:1, and they were of age 4-12 years. We determined the urinary levels of oxidative stress markers like thiobarbituric acid-reacting substances, lipid hydroperoxides, 4-hydroxy nonenal, protein carbonyls, sulfhydryl groups, total antioxidant capacity, total peroxide content, oxidative stress index, and also UA/Cr ratio in autistic children. RESULTS: The study observed a significant elevation in the level of oxidative stress markers in autistic children when compared with normal children. The level of antioxidants excreted in urine was found to be significantly low in autistic children. These findings when correlated with the degrees of severity, oxidative stress markers showed positive correlation with increasing order of severity (LFA>MFA>HFA), whereas antioxidants showed negative correlation. DISCUSSION: The study reveals that the urinary levels of oxidative stress markers can be considered as the measure of oxidative stress index in autistic children. The significant correlation between the severity of autism with urinary lipid peroxidation products also support the use of oxidative stress markers and antioxidants as biomarkers of autism.
Assuntos
Transtorno Autístico/urina , Estresse Oxidativo/fisiologia , Antioxidantes/metabolismo , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Peroxidação de Lipídeos/fisiologia , Peróxidos Lipídicos/urina , Masculino , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Oxidative stress-induced lipid peroxidation (LPO) leads to the formation of cytotoxic and genotoxic 2-alkenals. LPO products such as 4-hydroxy-2(E)-nonenal (HNE) and 4-oxo-2(E)-nonenal (ONE) have been the subject of many studies due to their association with the development of cardiovascular and neurodegenerative diseases, as well as cancer. LPO products are excreted in the urine after conjugation with glutathione (GSH) and subsequent metabolism to mercapturic acid (MA) conjugates. Urinary LPO-MA metabolites are stable end-product metabolites and have gained interest as non-invasive in vivo biomarkers of oxidative stress. This protocol describes a method for the quantitative analysis of LPO-MA metabolites in urine using isotope-dilution liquid chromatography coupled with electrospray tandem mass spectrometry (LC-MS/MS). Included are protocols for preparation of labeled LPO-MA conjugates from unlabeled LPO products and deuterium labeled MA.
Assuntos
Acetilcisteína/urina , Peróxidos Lipídicos/urina , Estresse Oxidativo , Biomarcadores/urina , Calibragem , Cromatografia Líquida , Humanos , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em TandemRESUMO
This study proposes the intravenous administration of glutathione (GSH) as a novel strategy to prevent contrast medium-induced renal oxidative stress. Renal oxidative stress is a critical cause of contrast-induced nephropathy (CIN). Recent reports have described that N-acetylcysteine (NAC) may prevent CIN by scavenging reactive oxygen species in the kidney. Twenty-one patients with reduced renal function who underwent coronary angiography (CAG) were equally assigned to the control, NAC and GSH (100 mg/min for 30 min before CAG) groups. CIN occurred in two patients, one in the control and the other in the NAC group. In the control group, the urinary lipid hydroperoxides (LOOHs) increased to 299.5 ± 94.4% of the baseline at 2 h after CAG (mean ± SE, p < 0.01). The increase in LOOHs was completely abolished in the GSH group (5.5 ± 8.8%, p = ns), but not in the NAC group (196.8 ± 81.3%, p < 0.05). In the control group, the serum GSH level fell by 9.4 ± 2.3% at 2 h after CAG (p < 0.01). The decrease was prevented in the GSH group (-1.8 ± 8.5%, p = ns), but not in the NAC group (-10.0 ± 3.3%, p < 0.05). The renal damage by contrast medium-induced oxidative stress occurs soon after CAG, and intravenous GSH is more effective in preventing the oxidative stress than oral NAC. This advantage may make GSH a potentially more effective therapeutic strategy against CIN.
Assuntos
Acetilcisteína/administração & dosagem , Antioxidantes/administração & dosagem , Meios de Contraste , Angiografia Coronária/efeitos adversos , Glutationa/administração & dosagem , Nefropatias/prevenção & controle , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Administração Oral , Idoso , Análise de Variância , Biomarcadores/sangue , Biomarcadores/urina , Distribuição de Qui-Quadrado , Creatinina/sangue , Feminino , Glutationa/sangue , Humanos , Infusões Intravenosas , Japão , Rim/metabolismo , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Peróxidos Lipídicos/urina , Masculino , Estudos Prospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Obesity has reached epidemic proportions in the United States. It is implicated in the development of a variety of chronic disease states and is associated with increased levels of inflammation and oxidative stress. The objective of this study is to examine the effect of Medifast's meal replacement program (MD) on body weight, body composition, and biomarkers of inflammation and oxidative stress among obese individuals following a period of weight loss and weight maintenance compared to a an isocaloric, food-based diet (FB). METHODS: This 40-week randomized, controlled clinical trial included 90 obese adults with a body mass index (BMI) between 30 and 50 kg/m2, randomly assigned to one of two weight loss programs for 16 weeks and then followed for a 24-week period of weight maintenance. The dietary interventions consisted of Medifast's meal replacement program for weight loss and weight maintenance, or a self-selected, isocaloric, food-based meal plan. RESULTS: Weight loss at 16 weeks was significantly better in the Medifast group (MD) versus the food-based group (FB) (12.3% vs. 6.9%), and while significantly more weight was regained during weight maintenance on MD versus FB, overall greater weight loss was achieved on MD versus FB. Significantly more of the MD participants lost >or= 5% of their initial weight at week 16 (93% vs. 55%) and week 40 (62% vs. 30%). There was no difference in satiety observed between the two groups during the weight loss phase. Significant improvements in body composition were also observed in MD participants compared to FB at week 16 and week 40. At week 40, both groups experienced improvements in biochemical outcomes and other clinical indicators. CONCLUSIONS: Our data suggest that the meal replacement diet plan evaluated was an effective strategy for producing robust initial weight loss and for achieving improvements in a number of health-related parameters during weight maintenance, including inflammation and oxidative stress, two key factors more recently shown to underlie our most common chronic diseases. TRIAL REGISTRATION: ClinicalTrials.gov NCT01011491.
Assuntos
Dieta Redutora/métodos , Alimentos , Obesidade/dietoterapia , Redução de Peso , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/urina , Composição Corporal , Proteína C-Reativa , Dieta Redutora/estatística & dados numéricos , Feminino , Humanos , Inflamação/sangue , Inflamação/urina , Peróxidos Lipídicos/urina , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Numerous studies have revealed the presence of oxidative stress in parasitic infections. However, such studies were lacking in the Malaysian population. Previously, we have provided evidence that oxidative stress is elevated in Malaysians infected with intestinal parasites. Stool examinations revealed that about 47.5% of them were infected with the polymorphic protozoa, Blastocystis hominis. However, they were found to have mixed infection with other intestinal parasites. METHODOLOGY: Therefore, in order to investigate the role of B. hominis alone in affecting oxidative stress status, here we compared the levels of oxidative stress biomarkers in urine and blood samples between uninfected and B. hominis-infected rats. RESULTS: Infected rats exhibited elevated levels of oxidative indices namely advanced oxidative protein products (AOPP), hydrogen peroxide (H2O2) and lipid hydroperoxide (LHP) indicating that their overall oxidative damage level was higher. Ferric reducing antioxidant power (FRAP) was elevated at the initial stage of infection but decreased significantly during the last week of study duration suggesting that the antioxidant status of the host may be overwhelmed by oxidative damage. CONCLUSION: To date, this is the first comprehensive in vivo study to provide evidence for Blastocystis infection to correlate with significant oxidative burst leading to oxidative stress.
Assuntos
Infecções por Blastocystis/metabolismo , Blastocystis hominis , Estresse Oxidativo , Animais , Infecções por Blastocystis/sangue , Infecções por Blastocystis/urina , Compostos Férricos/sangue , Compostos Férricos/metabolismo , Compostos Férricos/urina , Peróxido de Hidrogênio/metabolismo , Peróxidos Lipídicos/sangue , Peróxidos Lipídicos/metabolismo , Peróxidos Lipídicos/urina , Proteínas/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Degenerative diseases, immune impairment, and premature ageing commonly affect professional categories exposed to severe environmental and psychological stress. Among these, cosmonauts routinely experience extreme conditions due to microgravity, space radiation, altered oxygen supply, physical and mental fatigue during training, spaceflight, and post-flight. Long route aviation pilots display elevated oncogenic risk, connected with cosmic radiation overexposure, and high mortality rates for cardiovascular causes. Engine drivers, like pilots, are affected by health consequences of psycho-emotional stress, and burnout syndrome. The free radical (FR)/antioxidant (AO) imbalance is a common feature in all these pathological conditions. To assess the effective relevance of oxidative stress, we analyzed blood and urine reliable markers of FR production and AO defenses in 12 Russian cosmonauts, 55 airline pilots, 63 train engine drivers, and 50 age-matched controls by measuring the following: (a) lipophilic/hydrophilic low-molecular weight AO and AO enzyme activities, (b) nitric oxide, superoxide anion, hydroperoxide production, and (c) urinary catecholamine/serotonine metabolites and lipoperoxidation markers. Cosmonauts showed elevated granulocyte superoxide and nitric oxide production, increased erythrocyte superoxide dismutase activity and glutathione oxidation, and drastically decreased plasma/leucocyte lipophilic AO levels (P < 0.001-0.01). Aviation pilots, like train drivers, displayed a mild but constant oxidative stress, more pronounced in intercontinental routes pilots, and consistent with lymphocyte chromosomal alterations, DNA oxidation, and cardiovascular malfunction. Results obtained on these selected professionals operating under wearing conditions offer a solid molecular basis for advising the regular monitoring of clinical biochemistry laboratory markers of AO/FR status, to tailor individually specific AO supplementation and diet regimen, and monitor treatment outcomes.
Assuntos
Antioxidantes/metabolismo , Aviação , Senescência Celular , Exposição Ocupacional/efeitos adversos , Estresse Oxidativo , Ferrovias , Adulto , Catecolaminas/urina , Eritrócitos/metabolismo , Feminino , Radicais Livres/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Leucócitos/metabolismo , Peróxidos Lipídicos/urina , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/biossíntese , Serotonina/urina , Voo Espacial , Superóxidos/metabolismoRESUMO
OBJECTIVE: To evaluate the drug metabolizing enzyme CYP1A2 activity in pediatric hemoglobin E-beta-thalassemia patients, since CYP1A2 is responsible for the metabolism of a number of drugs. Alteration of its activity may have clinical consequences. MATERIAL AND METHOD: Twenty-three hemoglobin E-beta thalassemia pediatric patients and 24 age-matched controls were recruited in the present study. Caffeine in the form of a soft drink was orally administered as a test probe for CYP1A2 activity. Plasma collected at pre-dose and 6 hr after intake was analyzed for the levels of caffeine and paraxanthine, its major metabolite to represent the activity of CYPIA2. RESULTS: Biochemical markers, including blood glutathione and urinary lipid hydroperoxides indicated that patients were in an oxidant stress state. The plasma ratio of paraxanthine to caffeine was unchanged between patients and controls. Multiple regression analysis revealed that gender and the liver enzyme were the significant determinants of CYP1A2 activity (adjusted r2 = 0.48, p < 0.001). Male gender was associated with higher activity of CYP1A2 activity. CONCLUSION: The CYP1A2 activity is not apparently changed in thalassemia patients despite the presence of an oxidative stress state.
Assuntos
Cafeína/metabolismo , Citocromo P-450 CYP1A2/genética , Hemoglobina E/genética , Fígado/enzimologia , Talassemia beta/enzimologia , Cafeína/sangue , Estudos de Casos e Controles , Criança , Intervalos de Confiança , Citocromo P-450 CYP1A2/metabolismo , Feminino , Ferritinas/sangue , Glutationa/sangue , Hemoglobina E/metabolismo , Humanos , Peróxidos Lipídicos/urina , Masculino , Análise Multivariada , Estresse Oxidativo , Fatores Sexuais , Tailândia/epidemiologia , Teofilina/sangue , Transaminases/sangue , Talassemia beta/epidemiologiaRESUMO
Inflammatory events contribute to cisplatin-induced renal damage. Cisplatin promotes increased production of reactive oxygen species, which can activate nuclear factor-kappaB (NF-kappaB) that lead to increased expression of proinflammatory mediators which could intensify the cytotoxic effects of cisplatin. In this study, we evaluated the effect of parthenolide, a selective inhibitor of NF-kappaB, on renal damage caused by cisplatin use. A total of 94 male Wistar rats were divided into six groups: Group A (18 rats) were treated with saline; Group B (12 rats) received dimethylsulfoxide plus saline (the solvent for parthenolide); Group C (12 rats) received parthenolide (3mg/kg) plus saline; Group D (20 rats) received cisplatin (5mg/kg, i.p.); Group E (12 rats) received dimethylsulfoxide plus cisplatin (5mg/kg, i.p.); and Group F (21 rats) received parthenolide (3mg/kg) plus cisplatin (5mg/kg, i.p.). Dimethylsulfoxide or parthenolide were administered at 24h and 1h prior to cisplatin injection, and again at 24h and 48h after. At 2, 3 and 5 days after saline or cisplatin injection, blood and urine samples were collected for measurement of creatinine, sodium and potassium and the kidneys removed for histological, morphometric, electrophoretic mobility shift assay (EMSA), apoptosis and immunohistochemical studies. Cisplatin-treated rats presented higher plasma creatinine, as well as greater immunostaining for ED1 (macrophages/monocytes) and NF-kappaB in the renal cortices and outer medullae. The increase of NF-kappaB activation was confirmed by EMSA. Cisplatin-injected rats also presented higher urinary levels of lipid peroxidation and acute tubular necrosis. All of these alterations were reduced by treatment with parthenolide. This effect seems to be related, at least in part, to the restriction of renal inflammatory process observed in parthenolide+cisplatin treated rats.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/antagonistas & inibidores , Antineoplásicos/toxicidade , Cisplatino/antagonistas & inibidores , Cisplatino/toxicidade , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Sesquiterpenos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Ensaio de Desvio de Mobilidade Eletroforética , Taxa de Filtração Glomerular , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Nefropatias/patologia , Testes de Função Renal , Medula Renal/patologia , Túbulos Renais/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Peróxidos Lipídicos/urina , Masculino , NF-kappa B/metabolismo , Proteínas Nucleares/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Superóxidos/metabolismoRESUMO
We investigated the effects of long-term treatment with probucol, a hypolipidemic agent with antioxidative action, insulin, or their combination on renal damage in streptozotocin-induced diabetic rats fed a high cholesterol diet. Increases in urinary albumin and lipid peroxide excretions were observed in these diabetic rats, when both urinary parameters were measured at 8 and 15 weeks after streptozotocin administration. Daily treatment with probucol, insulin, or their combination markedly suppressed the increase in the 24 h urinary albumin and lipid peroxide excretions. Furthermore, glycogen degeneration of distal tubules, fatty degeneration of glomerular endothelium, and hypertrophy of glomeruli and mesangium were observed in the kidneys of the diabetic animals, when histopathological evaluation was performed at 4, 8 and 15 weeks (glomerular and mesangial hypertrophy was observed only at 15 weeks). Combined probucol and insulin treatment was the most effective in suppressing these renal histopathological changes. These results indicate that combined treatment with probucol and insulin is useful in preventing the progression of renal damage in diabetic rats. The possible mechanisms for the preventive effect of this combined treatment will be discussed.
Assuntos
Antioxidantes/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Insulina/farmacologia , Nefropatias/tratamento farmacológico , Probucol/farmacologia , Albuminúria , Animais , Anticolesterolemiantes/farmacologia , Glicemia , Colesterol/sangue , Colesterol na Dieta , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Sinergismo Farmacológico , Quimioterapia Combinada , Hipoglicemiantes/farmacologia , Nefropatias/etiologia , Nefropatias/metabolismo , Nefropatias/patologia , Peróxidos Lipídicos/urina , Masculino , Ratos , Ratos Sprague-Dawley , Triglicerídeos/sangueRESUMO
We previously reported that oxidative stress and renal tubular damage occur in chronic hyperoxaluric rats. However, the in vivo responses of renal epithelial cells after vitamin E administration and their correlations with calcium oxalate (CaOx) crystal formation have not been evaluated. Male Wistar rats received 0.75% ethylene glycol (EG) for 7, 21, or 42 days to induce CaOx deposition (EG group). Another group of EG-treated rats received 200 mg kg(-1) of vitamin E intraperitoneally (EG+E group) to evaluate its effect on hyperoxaluria. Urinary electrolytes and biochemistry and levels of lipid peroxides and enzymes were examined, together with serum vitamin E levels. Levels of the tubular markers, alpha and mu glutathione S-transferase, proliferating cell nuclear antigen (PCNA), osteopontinin (OPN), and Tamm-Horsfall protein (THP) were also measured, and TUNEL staining was performed to examine the viability of the tubular epithelium. There were no significant differences between the two age-matched controls either untreated or given vitamin E. Compared to untreated controls, tubular cell death was increased at all time points in EG rats with a gradual increase in CaOx crystals, whereas the number of PCNA-positive cells was only significantly increased on day 21. In EG+E rats, tubular cell death was decreased compared to the EG group, and cell proliferation was seen at all time points, while CaOx crystal deposition was decreased, but hyperoxaluria, urinary lipid peroxides, and enzymuria were unaffected. Vitamin E supplement prevented the loss of OPN and THP in renal tissues by EG and the reduction in their levels in the urine. The beneficial effect of vitamin E in reducing CaOx accumulation is due to attenuation of tubular cell death and enhancement of the defensive roles of OPN and THP.
Assuntos
Apoptose/efeitos dos fármacos , Oxalato de Cálcio/metabolismo , Cálculos Renais/metabolismo , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/metabolismo , Vitamina E/farmacologia , Acetilglucosaminidase/urina , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Apoptose/fisiologia , Proliferação de Células/efeitos dos fármacos , Cristalização , Etilenoglicol , Glutationa Transferase/metabolismo , Glicoproteínas/metabolismo , Cálculos Renais/induzido quimicamente , Cálculos Renais/tratamento farmacológico , Cálculos Renais/patologia , Túbulos Renais/citologia , Peróxidos Lipídicos/urina , Masculino , Mucoproteínas/metabolismo , Estresse Oxidativo , Ratos , Ratos Wistar , Uromodulina , Vitamina E/sangue , Vitamina E/uso terapêuticoRESUMO
BACKGROUND: Traditional coronary risk factors do not fully explain variations in the incidence of cardiovascular disease (CVD). Epidemiological studies have implicated perturbations in selenium, copper, and zinc metabolism in the aetiology of CVD. However, these studies have been principally undertaken in Caucasian populations, in whom trace element intake is generally sufficient. METHOD: We have measured serum and urine selenium, copper, and zinc; and superoxide dismutase, glutathione peroxidase, and lipid peroxide concentrations in 130 Saudi male subjects with established CVD, and 130 age-matched controls. RESULTS: Diabetes mellitus, positive smoking habit (p<0.0001 for both), and hypertension (p<0.05) were more prevalent among CVD patients. Urinary copper (p<0.0001) and zinc (p<0.05) were higher among controls. Serum selenium concentrations were lower among CVD patients (p<0.001), and a high proportion (52%) had selenium levels below 79mug/L compared to controls (22%) (p<0.0001). Conditional logistic regression analysis, showed the characteristics differentiating CVD patients from controls were serum zinc (odds ratio (OR) 0.92, confidence interval (CI) 0.85-0.99, p<0.05), serum copper/zinc ratio (OR 0.31, CI 0.10-0.96), serum selenium (OR 0.07, CI 0.02-0.31, p<0.0001), and urine selenium (OR 3.34, CI 1.40-7.99, p<0.01). CONCLUSION: Measures of trace metals status appear to be associated with the risk of atherosclerosis in a Saudi male population.
Assuntos
Aterosclerose , Cobre , Selênio , Oligoelementos , Zinco , Adulto , Fatores Etários , Idoso , Aterosclerose/sangue , Aterosclerose/urina , Cobre/sangue , Cobre/urina , Demografia , Dieta , Glutationa Peroxidase/sangue , Glutationa Peroxidase/urina , Humanos , Peróxidos Lipídicos/sangue , Peróxidos Lipídicos/urina , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Arábia Saudita , Selênio/sangue , Selênio/urina , Superóxido Dismutase/sangue , Superóxido Dismutase/urina , Oligoelementos/sangue , Oligoelementos/urina , Zinco/sangue , Zinco/urinaRESUMO
The article summarises data on the activity of tubular enzymes having marked organ-specific characteristics related to kidneys. They are N-acetyl-beta-D-glucosaminidase (NAG), its thermostable isoenzyme NAG B and beta-galactosidase localised in lysosomes. L-canavinine, ornithine aminotransferase having mitochondrial localization have also been discussed in the article. The authors have dealt also with the activity of lipoperaxidation processes having been assessed by an ammount of malonic dialdehyde in blood serum, erythrocytes and urine of 51 patients with progressive diabetes mellitus at the late stages of diabetic nephropathy.
Assuntos
Nefropatias Diabéticas/enzimologia , Túbulos Renais/enzimologia , Peroxidação de Lipídeos , Adulto , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/urina , Feminino , Humanos , Testes de Função Renal , Túbulos Renais/metabolismo , Peróxidos Lipídicos/sangue , Peróxidos Lipídicos/urina , Masculino , Pessoa de Meia-IdadeRESUMO
We have recently proposed total hydroxyoctadecadienoic acid (HODE) as a biomarker for oxidative stress in vivo. The biological samples such as plasma, urine, and tissues were first reduced and then saponified to convert the oxidation products of linoleate to HODE. In the present study, this method was applied to measure the oxidative damage induced by the administration of carbon tetrachloride to mice and also to evaluate the capacity of antioxidant to inhibit the above damage. alpha-Tocopherol transfer protein knock out (alpha-TTP-/-) mice were used to evaluate antioxidant effect in the absence of alpha-tocopherol. The intraperitoneal administration of carbon tetrachloride to mice induced the increase in HODE in liver and plasma, which was followed by an increase in plasma glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT). F2-isoprostanes, another prevailing biomarker, were also increased similarly, but their concentration was approximately two to three orders of magnitude smaller than that of HODE. The lipophilic antioxidants such as gamma-tocopherol, gamma-tocotrienol and 2,3-dihydro-5-hydroxy-4,6-di-tert-butyl-2,2-dipentylbenzofuran (BO-653) were effective in suppressing the formation of HODE.
Assuntos
Antioxidantes/farmacologia , Biomarcadores/análise , Tetracloreto de Carbono/toxicidade , Ácidos Graxos Insaturados/análise , Peroxidação de Lipídeos/efeitos dos fármacos , Alanina Transaminase/sangue , Animais , Antioxidantes/administração & dosagem , Ácido Ascórbico/sangue , Aspartato Aminotransferases/sangue , Benzofuranos/antagonistas & inibidores , Benzofuranos/sangue , Benzofuranos/farmacologia , Biomarcadores/sangue , Biomarcadores/metabolismo , Tetracloreto de Carbono/administração & dosagem , Proteínas de Transporte/genética , Cromatografia Líquida de Alta Pressão , Dieta , Dinoprosta/análogos & derivados , Dinoprosta/sangue , Ácidos Graxos Insaturados/sangue , Ácidos Graxos Insaturados/metabolismo , Genótipo , Injeções Intraperitoneais , Peróxidos Lipídicos/sangue , Peróxidos Lipídicos/urina , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Estresse Oxidativo , Organismos Livres de Patógenos Específicos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Tocotrienóis/antagonistas & inibidores , Tocotrienóis/sangue , Tocotrienóis/farmacologia , Ubiquinona/análogos & derivados , Ubiquinona/sangue , Vitamina E/administração & dosagem , Vitamina E/farmacologia , alfa-Tocoferol/sangueRESUMO
BACKGROUND/AIMS: Dipyridamole stimulates nitric oxide action via inhibition of phosphodiesterase and also has an antioxidant effect. ACE inhibitor reduces glomerular pressure and enhances NO action via increased bradykinin. Thus, we evaluated the effect of the combination of dipyridamole and ACE inhibitor in diabetic nephropathy. METHODS: Streptozotocin-induced diabetic rats at 2 weeks were treated with dipyridamole, quinapril or both. The expression of NOS and NAD(P)H oxidase p47phox was investigated using immunohistochemistry and western blot, and urinary albumin, cGMP and lipid peroxidation products (LPO) were measured at 4 weeks. RESULTS: NAD(P)H oxidase and urinary LPO were significantly enhanced in diabetes, and suppressed by each treatment to the same extent. The nNOS expression in macula densa and eNOS increased significantly with combination therapy compared to quinapril treatment alone contributing to an enhanced urinary excretion of cGMP and to maintain the creatinine clearance. Increased albuminuria in diabetes was reduced more effectively with combination therapy to the control level than with single treatments. CONCLUSION: Combination therapy with dipyridamole and quinapril suppressed urinary LPO via reduction of NAD(P)H oxidase increase in diabetes. The combination therapy reduced microalbuminuria to the control level and maintained creatinine clearance with enhanced nNOS and eNOS expression compared to quinapril alone.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/tratamento farmacológico , Dipiridamol/farmacologia , Isoquinolinas/farmacologia , Inibidores de Fosfodiesterase/farmacologia , Tetra-Hidroisoquinolinas , Albuminúria/urina , Animais , Glicemia/metabolismo , Western Blotting , Creatinina/sangue , Creatinina/urina , GMP Cíclico/urina , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/urina , Quimioterapia Combinada , Feminino , Imuno-Histoquímica , Rim/efeitos dos fármacos , Rim/enzimologia , Peróxidos Lipídicos/biossíntese , Peróxidos Lipídicos/urina , NADH NADPH Oxirredutases/metabolismo , NADPH Oxidases , Óxido Nítrico Sintase/biossíntese , Óxido Nítrico Sintase Tipo I , Fosfoproteínas/metabolismo , Quinapril , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
Chromium exists mostly in two valence states in nature: hexavalent chromium [chromium(VI)] and trivalent chromium [chromium(III)]. Chromium(VI) is commonly used in industrial chrome plating, welding, painting, metal finishes, steel manufacturing, alloy, cast iron and wood treatment, and is a proven toxin, mutagen and carcinogen. The mechanistic cytotoxicity of chromium(VI) is not completely understood, however, a large number of studies demonstrated that chromium(VI) induces oxidative stress, DNA damage, apoptotic cell death and altered gene expression. Conversely, chromium(III) is essential for proper insulin function and is required for normal protein, fat and carbohydrate metabolism, and is acknowledged as a dietary supplement. In this paper, comparative concentration- and time-dependent effects of chromium(VI) and chromium(III) were demonstrated on increased production of reactive oxygen species (ROS) and lipid peroxidation, enhanced excretion of urinary lipid metabolites, DNA fragmentation and apoptotic cell death in both in vitro and in vivo models. Chromium(VI) demonstrated significantly higher toxicity as compared with chromium(III). To evaluate the role of p53 gene, the dose-dependent effects of chromium(VI) were assessed in female C57BL/6Ntac and p53-deficient C57BL/6TSG p53 mice on enhanced production of ROS, lipid peroxidation and DNA fragmentation in hepatic and brain tissues. Chromium(VI) induced more pronounced oxidative damage in multiple target organs in p53 deficient mice. Comparative studies of chromium(III) picolinate and niacin-bound chromium(III), two popular dietary supplements, reveal that chromium(III) picolinate produces significantly more oxidative stress and DNA damage. Studies have implicated the toxicity of chromium picolinate in renal impairment, skin blisters and pustules, anemia, hemolysis, tissue edema, liver dysfunction; neuronal cell injury, impaired cognitive, perceptual and motor activity; enhanced production of hydroxyl radicals, chromosomal aberration, depletion of antioxidant enzymes, and DNA damage. Recently, chromium picolinate has been shown to be mutagenic and picolinic acid moiety appears to be responsible as studies show that picolinic acid alone is clastogenic. Niacin-bound chromium(III) has been demonstrated to be more bioavailable and efficacious and no toxicity has been reported. In summary, these studies demonstrate that a cascade of cellular events including oxidative stress, genomic DNA damage and modulation of apoptotic regulatory gene p53 are involved in chromium(VI)-induced toxicity and carcinogenesis. The safety of chromium(III) is largely dependent on the ligand, and adequate clinical studies are warranted to demonstrate the safety and efficacy of chromium(III) for human consumption.
Assuntos
Cloretos/metabolismo , Cloretos/toxicidade , Compostos de Cromo/metabolismo , Compostos de Cromo/toxicidade , Cromo/metabolismo , Cromo/toxicidade , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Fragmentação do DNA/efeitos dos fármacos , Fragmentação do DNA/fisiologia , Feminino , Citometria de Fluxo , Formazans/metabolismo , Genes p53/efeitos dos fármacos , Genes p53/fisiologia , Humanos , Radical Hidroxila/metabolismo , Células K562 , Peróxidos Lipídicos/metabolismo , Peróxidos Lipídicos/urina , Camundongos , Camundongos Endogâmicos C57BL , Oxirredução , Estresse Oxidativo/fisiologia , Ratos , Ratos Sprague-Dawley , Superóxidos/metabolismo , Sais de Tetrazólio/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/análiseRESUMO
Upregulation of adhesion molecules and neutrophil infiltration of venous valve cusps may be risk factors for chronic venous insufficiency. But studies that focus on the target organ (vein) fail to consider the influence of systemic inflammation on WBC behavior in the microcirculation. This study probes the gut-liver axis as a potential source of gut-derived oxidative stress and free radical production leading to white blood cell activation in chronic venous insufficiency. Venous hemodynamics (ambulatory venous pressure, air plethysmography, duplex) and gut-derived oxidative stress markers were studied in nine patients with chronic venous insufficiency (group I) and nine age- and sex-matched control subjects with no venous disease (group II). Group I had healed venous ulcers (class 5, CEAP) but near-normal ambulatory venous pressure, to eliminate high ambulatory venous pressure as a chronic venous insufficiency risk factor. Markers of gut-derived oxidative stress included: stool analysis; intestinal permeability; hepatic detoxification challenges with caffeine, salicylate, and acetaminophen; and urine lipid peroxides. Ambulatory venous pressure did not significantly differ (group I, 42.5 +/- 5.3 mm Hg; group II, 35.5 +/- 5.5 mm Hg; p = NS). Candida overgrowth in stool distinguished group I from group II (7/9 pts vs 1/9 pts, respectively; p = 0.015). Increased intestinal permeability (lactulose/mannitol ratio) was prevalent in both groups (group I 0.07 +/- 0.02, group II 0.17 +/- 0.08, p = NS; normal range, 0.01-0.03). Both groups showed similar incidence of elevated urine lipid peroxides (5/9 pts vs 6/9 pts, respectively; p = NS), yet group I exhibited underfunction of both sulfation (group I 16.8 +/- 2.9%, group II 43.3 +/- 11%, p<0.03; normal acetaminophen recovery 16-36%) and glucuronidation (group I 30.4 +/- 4.1%, group II 64.1 +/- 14.4%, p<0.04; normal acetaminophen recovery 27%-56%) relative to oxidative stress, perhaps an indicator of diminished antioxidant capacity in patients with chronic venous insufficiency. Gut dysbiosis (as indicated by stool yeast) and hepatic detoxification challenge pathway exhaustion may lead to subclinical, systemic inflammation and peripheral white blood cell adhesion in chronic venous insufficiency. Further exploration of the relationship between oxidative stress and venous disease is needed.
Assuntos
Fígado/metabolismo , Insuficiência Venosa/etiologia , Insuficiência Venosa/metabolismo , Adulto , Cafeína/metabolismo , Candida/metabolismo , Doença Crônica , Feminino , Glucuronidase/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Intestinos/microbiologia , Perna (Membro)/irrigação sanguínea , Peróxidos Lipídicos/urina , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Permeabilidade , Somatomedinas/metabolismoRESUMO
Eight 6-9 month old calves, showing clinical signs of intermittent haemoglobinuria, even after treatment with an antipiroplasmal drug (4,4-diamidinodiazaminobenzene diaceturate), were examined for oxidative damage to their erythrocytes and the presence of hemoprotozoa in blood smears. Four calves without signs of haemoglobinuria served as controls. The blood smears from three of the eight calves contained piroplasms for Theileria annulata. Irrespective of the presence of piroplasms in their blood smears, the calves with haemoglobinuria had significantly (p < 0.01) lower haemoglobin concentrations (Hb) and packed cell volumes (PCV). The lipid peroxide level in the erythrocytes, but not in the plasma, of calves with red urine was significantly (p <0.05) higher than that for the controls. It is concluded that haemoglobinuria, irrespective of the presence of piroplasms in blood smears, is associated with oxidative stress to erythrocytes and peroxidation of polyunsaturated fatty acids of cell membrane.
Assuntos
Doenças dos Bovinos/sangue , Diminazena/análogos & derivados , Eritrócitos/metabolismo , Hemoglobinúria/veterinária , Peróxidos Lipídicos/biossíntese , Animais , Antiprotozoários/uso terapêutico , Bovinos , Doenças dos Bovinos/parasitologia , Diminazena/uso terapêutico , Eritrócitos/parasitologia , Hematócrito/veterinária , Hemoglobinas/análise , Hemoglobinúria/sangue , Hemoglobinúria/parasitologia , Peróxidos Lipídicos/sangue , Peróxidos Lipídicos/urina , Malondialdeído/sangue , Theileria annulata , Theileriose/sangue , Theileriose/complicações , Theileriose/tratamento farmacológico , Theileriose/urinaRESUMO
Increased oxidative stress has been associated with work at high altitude; however, it is not known whether oxidative stress is a significant problem at moderate altitudes. The oxidative stress indicators, breath pentane (BP), 8-hydroxydeoxyguanosine (8-OHdG), oxygen radical absorption capacity (ORAC), 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), and lipid peroxides (LPO) were measured in breath, blood and urine samples of U.S. Marines engaged in moderate altitude ( approximately 3000 m) cold weather field training. The test subjects were divided into a placebo and four antioxidant supplement groups (n = 15/group) and received the following supplements for 28 d: 1) vitamin E, 440 alpha-tocopherol equivalents (alpha-TE); 2) vitamin A, 2000 retinol equivalents (RE) of beta-carotene; 3) vitamin C, 500 mg ascorbic acid; 4) a mixture of 440 alpha-TE, 2000 RE of beta-carotene, 500 mg ascorbic acid, 100 microg selenium and 30 mg zinc daily. Strenuous work ( approximately 23 MJ/d) in cold weather at moderate altitude was accompanied by increases in several indicators of oxidative stress that were not effectively controlled by conventional antioxidant supplements. The group receiving the antioxidant mixture exhibited lower BP (P < 0. 05) compared with those receiving single antioxidant supplements; however, not all markers of oxidative stress responded like BP. Because these markers did not respond in the same manner, it is important to include markers from more than one source to assess the effect of supplemental dietary antioxidants.
Assuntos
Altitude , Antioxidantes/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Esforço Físico/fisiologia , Adulto , Ácido Ascórbico/uso terapêutico , Testes Respiratórios , Temperatura Baixa , Método Duplo-Cego , Metabolismo Energético , Humanos , Peróxidos Lipídicos/sangue , Peróxidos Lipídicos/urina , Masculino , Malondialdeído/sangue , Malondialdeído/urina , Pentanos/química , Vitamina A/uso terapêutico , Vitamina E/uso terapêuticoRESUMO
Fructose intake has increased steadily during the past two decades. Fructose, like other reducing sugars, can react with proteins through the Maillard reaction (glycation), which may account for several complications of diabetes mellitus and accelerating aging. In this study, we evaluated the effect of fructose intake on some age-related variables. Rats were fed for 1 y a commercial nonpurified diet, and had free access to water or 250 g/L solutions of fructose, glucose or sucrose. Early glycation products were evaluated by blood glycated hemoglobin and fructosamine concentrations. Lipid peroxidation was estimated by urine thiobarbituric reactive substances. Skin collagen crosslinking was evaluated by solubilization in natural salt or diluted acetic acid solutions, and by the ratio between beta- and alpha-collagen chains. Advanced glycation end products were evaluated by collagen-linked fluorescence in bones. The ratio between type-III and type-I collagens served as an aging variable and was measured in denatured skin collagen. The tested sugars had no effect on plasma glucose concentrations. Blood fructose, cholesterol, fructosamine and glycated hemoglobin levels, and urine lipid peroxidation products were significantly higher in fructose-fed rats compared with the other sugar-fed and control rats. Acid-soluble collagen and the type-III to type-I ratio were significantly lower, whereas insoluble collagen, the beta to alpha ratio and collagen-bound fluorescence at 335/385 nm (excitation/emission) were significantly higher in fructose-fed rats than in the other groups. The data suggest that long-term fructose consumption induces adverse effects on aging; further studies are required to clarify the precise role of fructose in the aging process.