RESUMO
The antioxidant activities of QF808, a steam bark extract of Mangifera indica L., were studied on hydroxyl-mediated oxidation of bovine serum albumin (BSA) and in a hepatic microsome system. The extract was effective in reducing the oxidation of BSA, since its half- maximal inhibition concentration (IC(50)) was 0.0049% w/v in the inhibition of carbonyl group formation and lower than 0.0025% w/v in the inhibition of sulfhydryl group loss. QF808 inhibited lipid peroxidation which was initiated enzymatically by reduced nicotinamide adenine dinucleotide phosphate (NADPH), IC(50)= 0.00075% w/v, or non-enzymatically by ascorbic acid, IC(50) = 0.0126% w/v. The extract tested did not inhibit NADPH-dependent cytochrome P-450 reductase activity, since it had no effect on the oxidation rate of NADPH. These results suggest that QF808 has an antioxidant activity, probably due to its ability to scavenge free radicals involved in microsome lipid peroxidation. In addition, QF808 antioxidant profile in vitro is probably similar to its principal polyphenolic component, mangiferin, a glycosylated xanthone.
Assuntos
Antioxidantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Microssomos Hepáticos/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Sapindaceae , Soroalbumina Bovina/efeitos dos fármacos , Animais , Bovinos , Sistema Enzimático do Citocromo P-450/efeitos dos fármacos , Feminino , Concentração Inibidora 50 , Caules de Planta , Ratos , Ratos Sprague-DawleyRESUMO
Ozone has been used as a therapeutical agent and beneficial effects have been observed. However so far only a few biochemical and pharmacodynamic mechanisms have been elucidated. We demonstrate that controlled ozone administration may promote an oxidative preconditioning or adaptation to oxidative stress, preventing the damage induced by reactive oxygen species (ROS). Taking into account that diabetes is a disorder associated with oxidative stress, we postulate that ozone treatment in our experimental conditions might protect antioxidant systems and maintain, at a physiological level, other markers of endothelial cell damage associated with diabetic complications. Five groups of rats were classified as follows: (1) control group treated only with physiological saline solution; (2) positive control group using streptozotocin (STZ) as a diabetes inductor; (3) ozone group, receiving 10 treatments (1.1 mg kg(-1)), one per day after STZ-induced diabetes; (4) oxygen group (26 mg kg(-1)), one per day, as in group 3 but using oxygen only; (5) control ozone group, as group 3, but without STZ. The ozone treatment improved glycemic control and prevented oxidative stress, the increase of aldose reductase, fructolysine content and advanced oxidation protein products. Nitrite and nitrate levels were maintained without changes with regard to non-diabetic control. The results of this study show that repeated administration of ozone in non-toxic doses might play a role in the control of diabetes and its complications.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Oxidantes Fotoquímicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ozônio/uso terapêutico , Animais , Biomarcadores/análise , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/fisiopatologia , Endotélio Vascular/efeitos dos fármacos , Glicosilação/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Nitratos/metabolismo , Óxido Nítrico/biossíntese , Nitritos/metabolismo , Oxidantes Fotoquímicos/uso terapêutico , Oxirredução/efeitos dos fármacos , Ozônio/administração & dosagem , Proteínas/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
The time course of oxidative damage in different brain regions was investigated in the gerbil model of transient cerebral ischemia. Animals were subjected to both common carotid arteries occlusion for 5 min. After the end of ischemia and at different reperfusion times (2, 6, 12, 24, 48, 72, 96 h and 7 days), markers of lipid peroxidation, reduced and oxidized glutathione levels, glutathione peroxidase, glutathione reductase, manganese-dependent superoxide dismutase (MnSOD) and copper/zinc containing SOD (Cu/ZnSOD) activities were measured in hippocampus, cortex and striatum. Oxidative damage in hippocampus was maximal at late stages after ischemia (48-96 h) coincident with a significant impairment in glutathione homeostasis. MnSOD increased in hippocampus at 24, 48 and 72 h after ischemia, coincident with the marked reduction in the activity of glutathione-related enzymes. The late disturbance in oxidant-antioxidant balance corresponds with the time course of delayed neuronal loss in the hippocampal CA1 sector. Cerebral cortex showed early changes in oxidative damage with no significant impairment in antioxidant capacity. Striatal lipid peroxidation significantly increased as early as 2 h after ischemia and persisted until 48 h with respect to the sham-operated group. These results contribute significant information on the timing and factors that influence free radical formation following ischemic brain injury, an essential step in determining effective antioxidant intervention.
Assuntos
Encéfalo/metabolismo , Ataque Isquêmico Transitório/metabolismo , Estresse Oxidativo , Animais , Gerbillinae , Glutationa/metabolismo , Peróxidos Lipídicos/metabolismo , Masculino , Oxirredutases/metabolismo , Fatores de TempoRESUMO
The effect of oral administration of Mangifera indica L. extract (QF808) on ischemia-reperfusion-induced neuronal death in the gerbil hippocampal CA1 sector was examined. Oral administration of QF808 for 7 days dose-dependently protected against neuronal cell death following transient ischaemia and reperfusion as assessed by histopathology. In addition, locomotor activity assessment prior to ischaemia and 7 days after correlated well with the histological results. To evaluate redox alterations by reactive oxygen species, total sulfhydryl, non-protein sulfhydryl groups (NPSH), malondialdehyde + 4-hydroxyalkenals and total nitrogen oxide levels were assayed in hippocampus and cortex homogenates. QF808 treatment attenuated NPSH loss, nitrogen oxide levels and lipid peroxidation in the hippocampus. These results suggest that orally administered QF808 is absorbed across the blood-brain barrier and attenuates neuronal death of the hippocampal CA1 area after ischaemia-reperfusion. These protective effects are most likely due to the antioxidant activity of QF808.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Magnoliopsida , Fitoterapia , Extratos Vegetais/farmacologia , Animais , Antioxidantes/farmacologia , Encéfalo/metabolismo , Encéfalo/patologia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Morte Celular/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Gerbillinae , Masculino , Atividade Motora/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Células Piramidais/efeitos dos fármacos , Células Piramidais/metabolismo , Células Piramidais/patologiaRESUMO
An extract of Mangifera indica L. (Vimang) was tested in vitro for its antioxidant activity using commonly accepted assays. It showed a powerful scavenger activity of hydroxyl radicals and hypochlorous acid and acted as an iron chelator. The extract also showed a significant inhibitory effect on the peroxidation of rat-brain phospholipid and inhibited DNA damage by bleomycin or copper-phenanthroline systems.
Assuntos
Antioxidantes/farmacologia , Frutas , Peroxidação de Lipídeos/efeitos dos fármacos , Fitoterapia , Rosales , Animais , Dano ao DNA/efeitos dos fármacos , Extratos Vegetais/farmacologia , Caules de Planta , RatosRESUMO
On the basis that ozone (O3) can upregulate cellular antioxidant enzymes, a morphological, biochemical and functional renal study was performed in rats undergoing a prolonged treatment with O3 before renal ischaemia. Rats were divided into four groups: (1) control, a medial abdominal incision was performed to expose the kidneys; (2) ischaemia, in animals undergoing a bilateral renal ischaemia (30 min), with subsequent reperfusion (3 h); (3) O3 + ischaemia, as group 2, but with previous treatment with O3 (0.5 mg/kg per day given in 2.5 ml O2) via rectal administration for 15 treatments; (4) O2 + ischaemia, as group 3, but using oxygen (O2) alone. Biochemical parameters as fructosamine level, phospholipase A, and superoxide dismutases (SOD) activities, as well as renal plasma flow (RPF) and glomerular filtration rate (GFR), were measured by means of plasma clearance of p-amino-hippurate and inulin, respectively. In comparison with groups 1 and 3, the RPF and GFR were significantly decreased in groups 2 and 4. Interestingly, renal homogenates of the latter groups yielded significantly higher values of phospholipase A activity and fructosamine level in comparison with either the control (1) and the O3 (3) treated groups. Moreover renal SOD activity showed a significant increase in group 3 without significant differences among groups 1, 2 and 4. Morphological alterations of the kidney were present in 100%, 88% and 30% of the animals in groups 2, 4 and 3, respectively. It is proposed that the O3 protective effect can be ascribed to the substantial possibility of upregulating the antioxidant defence system capable of counteracting the damaging effect of ischaemia. These findings suggest that, whenever possible, ozone preconditioning may represent a prophylactic approach for minimizing renal damage before transplantation.
Assuntos
Isquemia , Rim/irrigação sanguínea , Ozônio/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Animais , Tolerância a Medicamentos , Frutosamina/metabolismo , Inulina/farmacocinética , Rim/efeitos dos fármacos , Rim/fisiologia , Masculino , Fosfolipases A/metabolismo , Ratos , Ratos Wistar , Reperfusão , Superóxido Dismutase/metabolismo , Temperatura , Ácido p-Aminoipúrico/farmacocinéticaRESUMO
There is some anecdotal evidence that oxygen-ozone therapy may be beneficial in some human diseases. However so far only a few biochemical and pharmacodynamic mechanisms have been elucidated. On the basis of preliminary data we postulated that controlled ozone administration would promote an oxidative preconditioning preventing the hepatocellular damage mediated by free radicals. Six groups of rats were classified as follows: (1) negative control, using intraperitoneal sunflower oil; (2) positive control using carbon tetrachloride (CCl4) as an oxidative challenge; (3) oxygen-ozone, pretreatment via rectal insufflation (15 sessions) and after it, CCl4; (4) oxygen, as group 3 but using oxygen only; (5) control oxygen-ozone, as group 3, but without CCl4; group (6) control oxygen, as group 5, but using oxygen only. We have evaluated critical biochemical parameters such as levels of transaminase, cholinesterase, superoxide dismutase, catalase, phospholipase A, calcium dependent ATPase, reduced glutathione, glucose 6 phosphate dehydrogenase and lipid peroxidation. Interestingly, in spite of CCl4 administration, group 3 did not differ from group 1, while groups 2 and 4 showed significant differences from groups 1 and 3 and displayed hepatic damage. To our knowledge these are the first experimental results showing that repeated administration of ozone in atoxic doses is able to induce an adaptation to oxidative stress thus enabling the animals to maintain hepatocellular integrity after CCl4 poisoning.