RESUMO
Despite the effectiveness and safety of anesthetics, some unanswered questions remain concerning their toxicity and effects on cellular redox balance. To test for possible toxic effects of balanced anesthesia maintained with the volatile anesthetic sevoflurane, we evaluated oxidative stress during and after general anesthesia in 15 adult patients without comorbidities who underwent elective minor surgical procedures. Venous blood samples were collected at baseline, before anesthesia (t0); after anesthesia induction and immediately before surgery (t1); 2h after the beginning of anesthesia (t2); and on the day following surgery (t3). Antioxidant defense was determined by fluorometry. Oxidative stress markers included oxidative DNA damage, evaluated by the alkaline comet assay, and plasma malondialdehyde (MDA), assessed by high performance liquid chromatography (HPLC). No increase in oxidized DNA damage or antioxidant defense was observed. Plasma MDA increased only at t3 compared with t2. Balanced sevoflurane-maintained anesthesia appears neither to damage DNA nor to alter redox status.
Assuntos
Anestésicos Inalatórios/administração & dosagem , Anestesia Balanceada/métodos , Procedimentos Cirúrgicos Eletivos , Éteres Metílicos/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Adolescente , Adulto , Anestesia Geral/efeitos adversos , Anestesia Geral/métodos , Anestésicos Inalatórios/efeitos adversos , Anestesia Balanceada/efeitos adversos , Dano ao DNA , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Éteres Metílicos/efeitos adversos , Oxirredução/efeitos dos fármacos , Complicações Pós-Operatórias/induzido quimicamente , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/metabolismo , Sevoflurano , Adulto JovemRESUMO
BACKGROUND/OBJECTIVES: Angelica keiskei is a green leafy vegetable rich in plant pigment phytochemicals such as flavonoids and carotenoids. This study examined bioavailability of flavonoids and carotenoids in Angelica keiskei and the alteration of the antioxidant performance in vivo. SUBJECTS AND MATERIALS: Absorption kinetics of phytochemicals in Angelica keiskei were determined in healthy older adults (> 60 y, n = 5) and subjects with metabolic syndrome (n = 5). Subjects consumed 5 g dry Angelica keiskei powder encapsulated in gelatin capsules with a low flavonoid and carotenoid liquid meal. Plasma samples were collected at baseline, 0.5, 1, 2, 3, 4, 5, 6, 7, and 8 h. Samples were analyzed for flavonoids and carotenoids using HPLC systems with electrochemical and UV detection, respectively, and for total antioxidant performance by fluorometry. RESULTS: After ingestion of Angelica keiskei increases in plasma quercetin concentrations were observed at 1-3 and 6-8 hr in the healthy group and at all time points in the metabolic syndrome group compared to baseline (P < 0.05). Plasma lutein concentrations were significantly elevated in both the healthy and metabolic syndrome groups at 8 hr (P < 0.05). Significant increases in total antioxidant performance were also observed in both the healthy and the metabolic syndrome groups compared to baseline (P < 0.05). CONCLUSIONS: Findings of this study clearly demonstrate the bioavailability of phytonutrients of Angelica keiskei and their ability to increase antioxidant status in humans.
RESUMO
Obesity is characterised by chronic low-grade inflammation, and lycopene has been reported to display anti-inflammatory effects. However, it is not clear whether lycopene supplementation modulates adipokine levels in vivo in obesity. To determine whether lycopene supplementation can regulate adipokine expression in obesity, male Wistar rats were randomly assigned to receive a control diet (C, n 6) ora hyperenergetic diet (DIO, n 12) for 6 weeks. After this period, the DIO animals were randomised into two groups: DIO (n 6) and DIO supplemented with lycopene (DIO + L, n 6). The animals received maize oil (C and DIO) or lycopene (DIO + L, 10 mg/kg body weight(BW) per d) by oral administration for a 6-week period. The animals were then killed by decapitation, and blood samples and epididymal adipose tissue were collected for hormonal determination and gene expression evaluation (IL-6, monocyte chemoattractant protein-1(MCP-1), TNF-α, leptin and resistin). There was no detectable lycopene in the plasma of the C and DIO groups. However, the mean lycopene plasma concentration was 24 nmol in the DIO + L group. Although lycopene supplementation did not affect BW or adiposity, it significantly decreased leptin, resistin and IL-6 gene expression in epididymal adipose tissue and plasma concentrations. Also, it significantly reduced the gene expression of MCP-1 in epididymal adipose tissue. Lycopene affects adipokines by reducing leptin, resistin and plasma IL-6 levels. These data suggest that lycopene may be an effective strategy in reducing inflammation in obesity.
Assuntos
Tecido Adiposo/metabolismo , Carotenoides/uso terapêutico , Inflamação/tratamento farmacológico , Interleucina-6/metabolismo , Leptina/metabolismo , Obesidade/tratamento farmacológico , Resistina/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Carotenoides/sangue , Carotenoides/farmacologia , Suplementos Nutricionais , Ingestão de Energia , Epididimo , Inflamação/etiologia , Inflamação/genética , Inflamação/metabolismo , Interleucina-6/genética , Leptina/genética , Licopeno , Masculino , Obesidade/complicações , Obesidade/genética , Obesidade/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Resistina/genéticaRESUMO
BACKGROUND: Conventional mechanical ventilation (CMV) is fundamental in acute respiratory distress syndrome (ARDS) treatment. Inhaled nitric oxide (INO), an adjunctive therapy, has been used with ventilation in an attempt to improve oxygenation and reduce lung injury. OBJECTIVE: To analyze the early effects of low INO dose on oxygenation, oxidative stress, inflammatory, and histopathological lung injury in a rabbit model of acute lung injury (ALI). METHODS: This was a prospective, controlled, in vivo animal laboratory study. Forty rabbits were instrumented and ventilated at F(IO(2)) 1.0. ALI was induced by tracheal infusion of warm saline (30 mL/kg, 38°C) and lung oxidative stress was assessed by total antioxidant performance (TAP) assay. Animals were assigned to groups: control group (no. = 10, low tidal volume [V(T)] = 6 mL/kg, PEEP = 5 cm H(2)O), ALI without INO (no-INO group, no. = 10, low V(T) = 6 mL/kg, PEEP = 10 cm H(2)O), ALI plus INO (INO group, no. = 10, low V(T) = 6 mL/kg, PEEP = 10 cm H(2)O, INO = 5 ppm). Plateau pressure was limited to 30 cm H(2)O in all groups. Ten non-instrumented animals (healthy group) were studied for TAP assay. Ventilatory and hemodynamic parameters were recorded every 30 min for 4 hours. RESULTS: After lung injury, the instrumented groups were worse than the control group for P(aO(2)) (control group 438 ± 87 mm Hg, no-INO group 80 ± 13 mm Hg, INO group 81 ± 24 mm Hg, P < .001). The INO group showed decreased lung inflammation by leukocyte count in lung lavage fluid (no-INO group 4.8 ± 1.64, control group 0.16 ± 0.15, INO group 0.96 ± 0.35 polymorphonuclear cells × 10(6)/bronchoalveolar lavage fluid/lung, P < .001), decreased histopathological injury score (no-INO group 5 [range 1-16], INO group 2 [range 0-5], control group 0 [range 0-3], P < .001), and better lung protection against oxidative injury than the no-INO group (healthy group 68 ± 8.7, control group 66.4 ± 6.8, INO group 56.3 ± 5.1, no-INO group 45.9 ± 3.4 percent protection/g protein, P < .001). CONCLUSIONS: INO attenuates oxidative stress and histopathological and inflammatory lung injury in a saline-lavaged rabbit ALI model.
Assuntos
Lesão Pulmonar Aguda , Óxido Nítrico , Estresse Oxidativo/efeitos dos fármacos , Oxigênio/metabolismo , Síndrome do Desconforto Respiratório , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/terapia , Administração por Inalação , Animais , Antioxidantes , Disponibilidade Biológica , Broncodilatadores/administração & dosagem , Broncodilatadores/farmacocinética , Quimioterapia Adjuvante , Relação Dose-Resposta a Droga , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Modelos Animais , Monitorização Fisiológica , Óxido Nítrico/administração & dosagem , Óxido Nítrico/farmacocinética , Estudos Prospectivos , Coelhos , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/terapiaRESUMO
Mechanical ventilation (MV) can induce lung oxidative stress, which plays an important role in pulmonary injury. This study compared protective conventional mechanical ventilation (CMV) and high-frequency oscillatory ventilation (HFOV) for oxygenation, oxidative stress, inflammatory and histopathological lung injury in a rabbit model of acute lung injury (ALI). Rabbits (n = 30) were ventilated at FiO(2) 1.0. Lung injury was induced by tracheal saline infusion (30 mL/kg, 38°C). Animals were randomly assigned to: (a) sham control (CG: tidal volume [V(T)] 6 mL/kg, positive end expiratory pressure [PEEP] 5 cmH(2)O, respiratory rate [RR] 40 ipm); (b) ALI + CMV (CMVG: V(T) 6 mL/kg, PEEP 10 cmH(2)O, RR 40 ipm); or (c) ALI + HFOV (HFG: mean airway pressure [Paw] 14 cmH(2)O, RR 10 Hz) groups. Lung oxidative stress was assessed by total antioxidant performance assay, inflammatory response by the number of polymorphonuclear leukocytes/bronchoalveolar lavage fluid/lung and pulmonary histological damage was quantified by a score. Ventilatory and hemodynamic parameters were recorded every 30 min. Both ALI groups showed worse oxygenation after lung injury induction. After four hours of ventilation, HFG showed better oxygenation (partial pressure of oxygen [PaO(2)] - CG: 465.9 ± 30.5 = HFG: 399.1 ± 98.2 > CMVG: 232.7 ± 104 mmHg, P < 0.05) and inflammatory responses (CMVG: 4.27 ± 1.50 > HFG: 0.33 ± 0.20 = CG: 0.16 ± 0.15; polymorphonuclear cells/bronchoalveolar lavage fluid/lung, P < 0.05), less histopathological injury score (CMVG: 5 [1-16] > HFG: 1 [0-5] > CG: 0 [0-3]; P < 0.05), and lower lung oxidative stress than CMVG (CG: 59.4 ± 4.52 = HFG: 69.0 ± 4.99 > CMVG: 47.6 ± 2.58% protection/g protein, P < 0.05). This study showed that HFOV had an important protective role in ALI. It improved oxygenation, reduced inflammatory process and histopathological damage, and attenuated oxidative lung injury compared with protective CMV under these experimental conditions considering the study limitations.
Assuntos
Lesão Pulmonar Aguda/terapia , Ventilação de Alta Frequência , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/fisiopatologia , Animais , Líquido da Lavagem Broncoalveolar/citologia , Modelos Animais de Doenças , Hemodinâmica/fisiologia , Inflamação/terapia , Pulmão/patologia , Pulmão/fisiopatologia , Complacência Pulmonar/fisiologia , Masculino , Neutrófilos/fisiologia , Estresse Oxidativo/fisiologia , Troca Gasosa Pulmonar , Coelhos , Respiração ArtificialRESUMO
The effect of pharmacological dose of α-tocopherol on heart health was determined in Wistar rats. Animals were randomly assigned to either C (control, n = 11) or E (α-tocopherol, n = 11) group. Animals received corn oil (C) or α-tocopherol dissolved in corn oil (250 mg α-tocopherol/[kg body wt/day]) (E) by gavage for a 7-week period. Rats underwent echocardiogram and were analyzed for cardiomyocyte histology and cardiac α-tocopherol absorption at the end of the study period. As compared to the C group, α-tocopherol-supplemented group showed significantly (p < 0.05) lower body weight (E, 412.8 g vs C, 480.3 g) and total cardiac weight (E, 0.94 g vs C, 1.08 g); cardiomyocyte histological impairment; smaller left ventricle (LV) (LV end-diastolic diameter (E, 7.22 mm vs C, 7.37 mm), lower LV systolic [left ventricle fractional shortening (E, 47.6% vs C, 53.6%) and ejection fraction ratio (E, 85.4 vs C, 89.9)] and diastolic [early peak velocities of diastolic transmitral flow (E, 64.6 cm/sec vs C, 75.1 cm/sec)] function. The α-tocopherol uptake in target tissue was confirmed by determination of α-tocopherol concentration medians in cardiac tissue (E, 109.91 nmol/kg vs C, 52.09 nmol/kg). The current study indicates that pharmacological dose of α-tocopherol supplementation can induce cardiotoxicity in healthy rats.
Assuntos
Coração/efeitos dos fármacos , alfa-Tocoferol/toxicidade , Animais , Ecocardiografia Doppler , Coração/fisiologia , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Ratos , Ratos Wistar , Redução de Peso , alfa-Tocoferol/farmacocinéticaRESUMO
The mechanism of doxorubicin-induced cardiotoxicity remains controversial. Wistar rats (n=96) were randomly assigned to a control (C), lycopene (L), doxorubicin (D), or doxorubicin+lycopene (DL) group. The L and DL groups received lycopene (5 mg/kg body wt/day by gavage) for 7 weeks. The D and DL groups received doxorubicin (4 mg/kg body wt intraperitoneally) at 3, 4, 5, and 6 weeks and were killed at 7 weeks for analyses. Myocardial tissue lycopene levels and total antioxidant performance (TAP) were analyzed by HPLC and fluorometry, respectively. Lycopene metabolism was determined by incubating (2)H(10)-lycopene with intestinal mucosa postmitochondrial fraction and lipoxygenase and analyzed with HPLC and APCI mass spectroscopy. Myocardial tissue lycopene levels in DL and L were similar. TAP adjusted for tissue protein were higher in myocardium of D than those of C (P=0.002). Lycopene metabolism study identified a lower oxidative cleavage of lycopene in D as compared to those of C. Our results showed that lycopene was not depleted in myocardium of lycopene-supplemented rats treated with doxorubicin and that higher antioxidant capacity in myocardium and less oxidative cleavage of lycopene in intestinal mucosa of doxorubicin-treated rats suggest an antioxidant role of doxorubicin rather than acting as a prooxidant.
Assuntos
Antioxidantes/metabolismo , Carotenoides/farmacocinética , Doxorrubicina/farmacologia , Coração/efeitos dos fármacos , Miocárdio/metabolismo , Animais , Carotenoides/química , Carotenoides/metabolismo , Catálise , Cromatografia Líquida , Doxorrubicina/química , Cinética , Licopeno , Solanum lycopersicum/química , Masculino , Espectrometria de Massas , Estrutura Molecular , Oleandomicina/farmacocinética , Oxirredução , Ratos , Ratos Wistar , Tetraciclina/farmacocinéticaRESUMO
Using the post-mitochondrial fraction of rat intestinal mucosa, we have investigated lycopene metabolism. The incubation media was composed of NAD+, KCI, and DTT with or without added lipoxygenase. The addition of lipoxygenase into the incubation significantly increased the production of lycopene metabolites. The enzymatic incubation products of 2H10 lycopene were separated using high-performance liquid chromatography and analyzed by UV/Vis spectrophotometer and atmospheric pressure chemical ionization-mass spectroscopy. We have identified two types of products: cleavage products and oxidation products. The cleavage products are likely: (1) 3-keto-apo-13-lycopenone (C18H24O2 or 6,10,14-trimethyl-12-one-3,5,7,9,13-pentadecapentaen-2-one) with lambdamax = 365 nm and m/z =272 and (2) 3,4-dehydro-5,6-dihydro-15-apo-lycopenal (C20H28O or 3,7,11,15-tetramethyl-2,4,6,8,12,14-hexadecahexaen-l-al) with lambdamax= 380 nm and m/z = 284. The oxidative metabolites are likely: (3) 2-ene-5,8-lycopenal-furanoxide (C37H50O) with lambdamax = 415 nm, 435 nm, and 470 nm, and m/z = 510; (4) lycopene-5, 6, 5', 6'-diepoxide (C40H56O2) with lambdamax = 415 nm, 440 nm, and 470 nm, and m/z =568; (5) lycopene-5,8-furanoxide isomer (I) (C40H56O2) with lambdamax = 410 nm, 440 nm, and 470 nm, and m/z = 552; (6) lycopene-5,8-epoxide isomer (II) (C40H56O) with lambdamax = 410, 440, 470 nm, and m/z = 552; and (7) 3-keto-lycopene-5',8'-furanoxide (C40H54O2) with lambdamax = 400 nm, 420 nm, and 450 nm, and m/z = 566. These results demonstrate that both central and excentric cleavage of lycopene occurs in the rat intestinal mucosa in the presence of soy lipoxygenase.
Assuntos
Carotenoides/metabolismo , Animais , Carotenoides/análise , Cromatografia Líquida de Alta Pressão , Mucosa Intestinal/metabolismo , Lipoxigenase/metabolismo , Licopeno , Masculino , Espectrometria de Massas , Oxirredução , RatosRESUMO
Using the post-mitochondrial fraction of rat intestinal mucosa, we have investigated lycopene metabolism. The incubation media was composed of NAD(+), KCl, and DTT with or without added lipoxygenase. The addition of lipoxygenase into the incubation significantly increased the production of lycopene metabolites. The enzymatic incubation products of (2)H(10) lycopene were separated using high-performance liquid chromatography and analyzed by UV/Vis spectrophotometer and atmospheric pressure chemical ionization-mass spectroscopy. We have identified two types of products: cleavage products and oxidation products. The cleavage products are likely: (1) 3-keto-apo-13-lycopenone (C(18)H(24)O(2) or 6,10,14-trimethyl-12-one-3,5,7,9,13-pentadecapentaen-2-one) with lambdamax = 365 nm and m/z = 272 and (2) 3,4-dehydro-5,6-dihydro-15,15'-apo-lycopenal (C(20)H(28)O or 3,7,11,15-tetramethyl-2,4,6,8,12,14-hexadecahexaen-1-al) with lambdamax = 380 nm and m/z = 284. The oxidative metabolites are likely: (3) 2-apo-5,8-lycopenal-furanoxide (C(37)H(50)O) with lambdamax = 415 nm, 435 nm, and 470 nm, and m/z = 510; (4) lycopene-5, 6, 5', 6'-diepoxide (C(40)H(56)O(2)) with lambdamax = 415 nm, 440 nm, and 470 nm, and m/z = 568; (5) lycopene-5,8-furanoxide isomer (I) (C(40)H(56)O) with lambdamax = 410 nm, 440nm, and 470 nm, and m/z = 552; (6) lycopene-5,8-epoxide isomer (II) (C(40)H(56)O) with lambdamax = 410, 440, 470 nm, and m/z = 552; and (7) 3-keto-lycopene-5',8'-furanoxide (C(40)H(54)O(2)) with lambdamax = 400 nm, 420 nm, and 450 nm, and m/z = 566. These results demonstrate that both central and excentric cleavage of lycopene occurs in the rat intestinal mucosa in the presence of soy lipoxygenase.