RESUMEN
Evidences has suggested that in the early life the innate immune system presents plasticity and the time and dose-adequate stimuli in this phase may program long-lasting immunological responses that persist until adulthood. We aimed to evaluate whether LPS challenge in early childhood period may modulate brain alterations after sepsis in adult life. Experiments were performed to evaluate the LPS challenge in early childhood or adult period on acute and long-term brain alterations after model of sepsis by cecal ligation and perforation (CLP) in adult life. Wistar rats were divided in saline+sham, LPS+sham, saline+CLP and LPS+CLP groups to determine cytokine levels and nitrite/nitrate concentration in cerebrospinal fluid (CSF); oxidative damage, activity of antioxidant enzymes (superoxide dismutase-SOD and catalase-CAT); blood brain barrier (BBB) permeability; myeloperoxidase (MPO) and epigenetic enzymes activities in the hippocampus and prefrontal cortex (at 24 h after CLP) and cognitive function, survival and brain-derived neurotrophic factor (BDNF) level (at ten days after CLP). LPS-preconditioning in early life could lead to decreased levels of TNF-α and IL-6 and oxidative damage parameters in the brain after CLP in adult rats. In addition, LPS-preconditioning in early life increase CAT activity, attenuates the BBB permeability and epigenetic enzymes alterations and in long term, improves the memory, BDNF levels and survival. In conclusion, rats submitted to CLP in adulthood displayed acute neuroinflammation, neurochemical and epigenetic alteration improvement accompanied in long term by an increase in survival, neurotrophin level and memory performance when preconditioned with LPS in the early life.
Asunto(s)
Encéfalo/inmunología , Mediadores de Inflamación/metabolismo , Lipopolisacáridos/toxicidad , Neuroinmunomodulación/inmunología , Neuroprotección/inmunología , Sepsis/inmunología , Factores de Edad , Animales , Encéfalo/efectos de los fármacos , Masculino , Neuroinmunomodulación/efectos de los fármacos , Neuroprotección/efectos de los fármacos , Ratas , Ratas Wistar , Sepsis/inducido químicamenteRESUMEN
OBJECTIVES: Sepsis is a severe organic dysfunction caused by an infection that affects the normal regulation of several organ systems, including the central nervous system. Inflammation and oxidative stress play crucial roles in the development of brain dysfunction in sepsis. The aim of this study was to determine the effect of a fish oil (FO)-55-enriched lipid emulsion as an important anti-inflammatory compound on brain dysfunction in septic rats. METHODS: Wistar rats were subjected to sepsis by cecal ligation and perforation (CLP) or sham (control) and treated orally with FO (600 µL/kg after CLP) or vehicle (saline; sal). Animals were divided into sham+sal, sham+FO, CLP+sal and CLP+FO groups. At 24 h and 10 d after surgery, the hippocampus, prefrontal cortex, and total cortex were obtained and assayed for levels of interleukin (IL)-1ß and IL-10, blood-brain barrier permeability, nitrite/nitrate concentration, myeloperoxidase activity, thiobarbituric acid reactive species formation, protein carbonyls, superoxide dismutase and catalase activity, and brain-derived neurotrophic factor levels. Behavioral tasks were performed 10 d after surgery. RESULTS: FO reduced BBB permeability in the prefrontal cortex and total cortex of septic rats, decreased IL-1ß levels and protein carbonylation in all brain structures, and diminished myeloperoxidase activity in the hippocampus and prefrontal cortex. FO enhanced brain-derived neurotrophic factor levels in the hippocampus and prefrontal cortex and prevented cognitive impairment. CONCLUSIONS: FO diminishes the negative effect of polymicrobial sepsis in the rat brain by reducing inflammatory and oxidative stress markers.
Asunto(s)
Antiinflamatorios/farmacología , Disfunción Cognitiva/prevención & control , Aceites de Pescado/farmacocinética , Estrés Oxidativo/efectos de los fármacos , Sepsis/psicología , Animales , Biomarcadores/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Encéfalo/efectos de los fármacos , Enfermedades del Ciego/complicaciones , Enfermedades del Ciego/microbiología , Ciego/irrigación sanguínea , Ciego/microbiología , Disfunción Cognitiva/microbiología , Modelos Animales de Enfermedad , Emulsiones , Lóbulo Frontal/efectos de los fármacos , Interleucina-1beta/metabolismo , Perforación Intestinal/complicaciones , Perforación Intestinal/microbiología , Ligadura/efectos adversos , Masculino , Permeabilidad , Carbonilación Proteica/efectos de los fármacos , Ratas , Ratas Wistar , Sepsis/etiología , Sepsis/microbiologíaRESUMEN
Complex regional pain syndrome type I (CRPS-I) is a chronic painful condition. We investigated whether manual therapy (MT), in a chronic post-ischemia pain (CPIP) model, is capable of reducing pain behavior and oxidative stress. Male Swiss mice were subjected to ischemia-reperfusion (IR) to mimic CRPS-I. Animals received ankle joint mobilization 48h after the IR procedure, and response to mechanical stimuli was evaluated. For biochemical analyses, mitochondrial function as well as oxidative stress thiobarbituric acid reactive substances (TBARS), protein carbonyls, antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) levels were determined. IR induced mechanical hyperalgesia which was subsequently reduced by acute MT treatment. The concentrations of oxidative stress parameters were increased following IR with MT treatment preventing these increases in malondialdehyde (MDA) and carbonyls protein. IR diminished the levels of SOD and CAT activity and MT treatment prevented this decrease in CAT but not in SOD activity. IR also diminished mitochondrial complex activity, and MT treatment was ineffective in preventing this decrease. In conclusion, repeated sessions of MT resulted in antihyperalgesic effects mediated, at least partially, through the prevention of an increase of MDA and protein carbonyls levels and an improvement in the antioxidant defense system.
RESUMEN
BACKGROUND: Biomedical research has recently incorporated bioceramics applications into new health care approaches. OBJECTIVE: This study evaluated the effect of far infrared-emitting bioceramics wraps in the treatment of intermittent claudication. METHODS: This is a randomized double-blind placebo-controlled pilot study. Thirty-five patients met the criteria and were randomized into either control (placebo wraps) or bioceramics group (far infrared emitting-ceramics wraps) and assessed over a 90-day period for the following outcomes: six-minute walk test (6MWT), ankle-brachial index (ABI), Flow-mediated arterial dilation (FMD), quality of life and claudication. Oxidative stress and inflammatory biomarkers were measured in plasma of patients. RESULTS: Intervention induced a decrease in oxidative stress, with significant lower levels of reactive substances to thiobarbituric acid (TBARS), as well as increase in superoxide dismutase and catalase enzyme activities. There was an increase in the environment subscale of the quality of life questionnaire. No statistically significant differences were found in the inflammatory cytokines, 6MWT, ABI and FMV evaluations. CONCLUSIONS: In Sum, FIR treatment improved oxidative stress profile and quality-of-life of patients with intermittent claudication. The study was registered into the ensaiosclinicos.gov.br (Registro Brasileiro de Ensaios Clínicos [ReBEC]) (RBR-7nr6sy register number).
Asunto(s)
Antioxidantes , Biomarcadores/sangre , Rayos Infrarrojos/uso terapéutico , Claudicación Intermitente/terapia , Calidad de Vida , Índice Tobillo Braquial , Método Doble Ciego , Humanos , Inflamación/sangre , Claudicación Intermitente/diagnóstico , Estrés Oxidativo , Proyectos Piloto , Superóxido Dismutasa/sangre , Tiobarbitúricos/sangre , Resultado del Tratamiento , CaminataRESUMEN
Sepsis is caused by a dysregulated host response to infection, often associated with acute central nervous system (CNS) dysfunction, which results in long-term cognitive impairment. Dimethyl fumarate (DMF) is an important agent against inflammatory response and reactive species in CNS disorders. Evaluate the effect of DMF on acute and long-term brain dysfunction after experimental sepsis in rats. Male Wistar rats were submitted to the cecal ligation and puncture (CLP) model. The groups were divided into sham (control) + vehicle, sham + NAC, sham + DMF, CLP + vehicle, CLP + NAC, and CLP + DMF. The animals were treated with DMF (15 mg/kg at 0 and 12 h after CLP, per gavage) and the administration of n-acetylcysteine (NAC) (20 mg/kg; 3, 6, and 12 h after CLP, subcutaneously) was used as positive control. Twenty-four hours after CLP, cytokines, myeloperoxidase (MPO), nitrite/nitrate (N/N), oxidative damage to lipids and proteins, and antioxidant enzymes were evaluated in the hippocampus, total cortex, and prefrontal cortex. At 10 days after sepsis induction, behavioral tests were performed to assess cognitive damage. We observed an increase in cytokine levels, MPO activity, N/N concentration, and oxidative damage, a reduction in SOD and GPx activity in the brain structures, and cognitive damage in CLP rats. DMF treatment was effective in reversing these parameters. DMF reduces sepsis-induced neuroinflammation, oxidative stress, and cognitive impairment in rats subjected to the CLP model.
Asunto(s)
Trastornos del Conocimiento , Dimetilfumarato/uso terapéutico , Inmunosupresores/uso terapéutico , Inflamación/tratamiento farmacológico , Inflamación/etiología , Estrés Oxidativo/efectos de los fármacos , Sepsis/complicaciones , Animales , Catalasa/metabolismo , Trastornos del Conocimiento/complicaciones , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/terapia , Citocinas/metabolismo , Modelos Animales de Enfermedad , Conducta Exploratoria/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Infiltración Neutrófila/efectos de los fármacos , Nitratos/metabolismo , Nitritos/metabolismo , Carbonilación Proteica/efectos de los fármacos , Ratas , Ratas Wistar , Reconocimiento en Psicología/efectos de los fármacos , Superóxido Dismutasa/metabolismoRESUMEN
Evidence suggest that prenatal immune system disturbance contributes largely to the pathophysiology of neuropsychiatric disorders. We investigated if maternal immune activation (MIA) could induce inflammatory alterations in fetal brain and pregnant rats. Adult rats subjected to MIA also were investigated to evaluate if ketamine potentiates the effects of infection. On gestational day 15, Wistar pregnant rats received lipopolysaccharide (LPS) to induce MIA. After 6, 12 and 24â¯h, fetus brain, placenta, and amniotic fluid were collected to evaluate early effects of LPS. MIA increased oxidative stress and expression of metalloproteinase in the amniotic fluid and fetal brain. The blood brain barrier (BBB) integrity in the hippocampus and cortex as well integrity of placental barrier (PB) in the placenta and fetus brain were dysregulated after LPS induction. We observed elevated pro- and anti-inflammatory cytokines after LPS in fetal brain. Other group of rats from postnatal day (PND) 54 after LPS received injection of ketamine at the doses of 5, 15, and 25â¯mg/kg. On PND 60 rats were subjected to the memories tests, spontaneous locomotor activity, and pre-pulse inhibition test (PPI). Rats that receive MIA plus ketamine had memory impairment and a deficit in the PPI. Neurotrophins were increased in the hippocampus and reduced in the prefrontal cortex in the LPS plus ketamine group. MIA induced oxidative stress and inflammatory changes that could be, at least in part, related to the dysfunction in the BBB and PB permeability of pregnant rats and offspring. Besides, this also generates behavioral deficits in the rat adulthood's that are potentiated by ketamine.
Asunto(s)
Conducta Animal , Barrera Hematoencefálica/inmunología , Encéfalo , Citocinas/metabolismo , Antagonistas de Aminoácidos Excitadores/farmacología , Inflamación/inmunología , Ketamina/farmacología , Lipopolisacáridos/farmacología , Trastornos de la Memoria , Placenta/inmunología , Complicaciones del Embarazo/inmunología , Inhibición Prepulso , Animales , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Encéfalo/efectos de los fármacos , Encéfalo/inmunología , Encéfalo/fisiopatología , Embrión de Mamíferos , Femenino , Inflamación/etiología , Masculino , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/inmunología , Trastornos de la Memoria/fisiopatología , Embarazo , Complicaciones del Embarazo/inducido químicamente , Inhibición Prepulso/efectos de los fármacos , Inhibición Prepulso/fisiología , Ratas , Ratas WistarRESUMEN
Neurological dysfunction as a result of neuroinflammation has been reported in sepsis and cause high mortality. High levels of cytokines stimulate the formation of neurotoxic metabolites by kynurenine (KYN) pathway. Vitamin B6 (vit B6) has anti-inflammatory and antioxidant properties and also acts as a cofactor for enzymes of the KYN pathway. Thus, by using a relevant animal model of polymicrobial sepsis, we studied the effect of vit B6 on the KYN pathway, acute neurochemical and neuroinflammatory parameters, and cognitive dysfunction in rats. Male Wistar rats (250-300 g) were submitted to cecal ligation and perforation (CLP) and divided into sham + saline, sham + vit B6, CLP + saline, and CLP + vit B6 (600 mg/kg, s.c.) groups. Twenty-four hours later, the prefrontal cortex and hippocampus were removed for neurochemical and neuroinflammatory analyses. Animals were followed for 10 days to determine survival rate, when cognitive function was assessed by behavioral tests. Vitamin B6 interfered in the activation of kynurenine pathway, which led to an improvement in neurochemical and neuroinflammatory parameters and, consequently, in the cognitive functions of septic animals. Thus, the results indicate that vit B6 exerts neuroprotective effects in acute and late consequences after sepsis.
Asunto(s)
Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/metabolismo , Quinurenina/metabolismo , Sepsis/tratamiento farmacológico , Sepsis/microbiología , Vitamina B 6/uso terapéutico , Animales , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Disfunción Cognitiva/patología , Citocinas/metabolismo , Metabolismo Energético/efectos de los fármacos , Inflamación/patología , Mediadores de Inflamación/metabolismo , Estimación de Kaplan-Meier , Peroxidación de Lípido/efectos de los fármacos , Masculino , Nitratos/metabolismo , Nitritos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Permeabilidad , Peroxidasa/metabolismo , Carbonilación Proteica/efectos de los fármacos , Ratas Wistar , Triptófano/metabolismo , Vitamina B 6/farmacologíaRESUMEN
Sepsis is a complication of an infection which imbalance the normal regulation of several organ systems, including the central nervous system (CNS). Evidence points towards inflammation and oxidative stress as major steps associated with brain dysfunction in sepsis. Thus, we investigated the α-lipoic acid (ALA) effect as an important antioxidant compound on brain dysfunction in rats. Wistar rats were subjected to sepsis by cecal ligation and perforation (CLP) or sham (control) and treated orally with ALA (200 mg/kg after CLP) or vehicle. Animals were divided into sham + saline, sham + ALA, CLP + saline and CLP + ALA groups. Twelve, 24 h and 10 days after surgery, the hippocampus, prefrontal cortex and cortex were obtained and assayed for levels of TNF-α and IL-1ß, blood brain barrier (BBB) permeability, nitrite/nitrate concentration, myeloperoxidase (MPO) activity, thiobarbituric acid reactive species (TBARS) formation, protein carbonyls, superoxide dismutase (SOD) and catalase (CAT) activity and neurotrophins levels. Behavioral tasks were performed 10 days after surgery. ALA reduced BBB permeability and TNF-α levels in hippocampus in 24 h and IL-1ß levels and MPO activity in hippocampus and prefrontal cortex in 24 h. ALA reduced nitrite/nitrate concentration and lipid peroxidation in 24 h in all structures and protein carbonylation in 12 and 24 h in hippocampus and cortex. CAT activity increased in the hippocampus and cortex in all times. ALA enhanced NGF levels in hippocampus and cortex and prevented cognitive impairment. Our data demonstrates that ALA reduces the consequences of polymicrobial sepsis in rats by decreasing inflammatory and oxidative stress parameters in the brain.
Asunto(s)
Antioxidantes/uso terapéutico , Disfunción Cognitiva/tratamiento farmacológico , Coinfección/tratamiento farmacológico , Mediadores de Inflamación/antagonistas & inhibidores , Sepsis/tratamiento farmacológico , Ácido Tióctico/uso terapéutico , Enfermedad Aguda , Animales , Antioxidantes/farmacología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Disfunción Cognitiva/metabolismo , Coinfección/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Mediadores de Inflamación/metabolismo , Masculino , Distribución Aleatoria , Ratas , Ratas Wistar , Sepsis/metabolismo , Ácido Tióctico/farmacología , Factores de TiempoRESUMEN
Despite advances in antimicrobial therapy and advanced critical care neonatal bacterial meningitis has a mortality rate of over 10% and induces neurological sequelae in 20-50% of cases. Escherichia coli K1 (E. coli K1) is the most common gram-negative organism causing neonatal meningitis and is the second most common cause behind group B streptococcus. We previously reported that an E. coli K1 experimental meningitis infection in neonatal rats resulted in habituation and aversive memory impairment and a significant increase in cytokine levels in adulthood. In this present study, we investigated the oxidative stress profile including malondialdehyde (MDA) levels, carbonyl protein formation, myeloperoxidase activity (MPO) activity, superoxide dismutase (SOD) activity and catalase (CAT) activity 6, 12, 24, 48, 72 and 96h after E. coli K1 experimental meningitis infection. In addition, sulfhydryl groups, nitrite and nitrate levels and activity of the mitochondrial respiratory chain enzymes were also measured in the frontal cortex and hippocampus of neonatal rats. The results from this study demonstrated a significant increase in MDA, protein carbonyls and MPO activity and a simultaneous decrease in SOD activity in the hippocampus of the neonatal meningitis survivors but the same was not observed in frontal cortex. In addition, we also observed a significant increase in complex IV activity in the hippocampus and frontal cortex of meningitis survivor rats. Thus, the results from this study reaffirmed the possible role of oxidative stress, nitric oxide and its related compounds in the complex pathophysiology of E. coli K1-induced bacterial meningitis.
Asunto(s)
Escherichia coli/patogenicidad , Lóbulo Frontal/metabolismo , Hipocampo/metabolismo , Meningitis por Escherichia coli/metabolismo , Estrés Oxidativo/fisiología , Animales , Animales Recién Nacidos , Modelos Animales de Enfermedad , Lóbulo Frontal/enzimología , Hipocampo/enzimología , Masculino , Malondialdehído/metabolismo , Meningitis por Escherichia coli/enzimología , Peroxidasa/metabolismo , Ratas , Ratas WistarRESUMEN
CONTEXT: Dillenia indica Linn. (Dilleniaceae) is traditionally used to treat skin inflammation. OBJECTIVE: This study evaluated the healing effect of Dillenia indica fruit extracts on induced psoriasis-like wounds in Wistar rats. MATERIALS AND METHODS: Extracts were standardized to betulinic acid, including an aqueous ethanolic extract (AEE), ethyl acetate extract (EAE) and petroleum ether extract. Effects against lipid peroxidation were assessed in vitro. Wounds were created at rat tails (n = 12). Topical treatments were applied once daily for 7 days (1 mL of AEE or EAE at 5 or 50 mg/mL). Maximal dose was defined by the extract solubility. A 10-fold lower dose was also tested. Positive and negative controls were treated with clobetasol (0.5 mg/mL) or excipient. Half of each group was euthanized for histology. The remaining animals were observed for 20 days for wound measurements. RESULTS: Yields of AEE and EAE were 4.3 and 0.7%, respectively. Betulinic acid concentrations in AEE and EAE were 4.6 and 107.6 mg/g. Extracts neutralized lipid peroxidation in vitro at 0.02 µg/mL, accelerating healing at 50 mg/mL. Complete healing in mice treated with AEE occurred 16 days after wound induction. This time was 14 and 12 days in mice treated with EAE and clobetasol. Compared to orthokeratosis, parakeratosis was reduced by AEE (25%), EAE (45%) and clobetasol (55%). EAE caused superior protection against biomolecules oxidation of skin compared to AEE. DISCUSSION AND CONCLUSION: EAE exhibited activity closer to that of clobetasol. Betulinic acid may be an active constituent, which should be assessed in future studies.
Asunto(s)
Antiinflamatorios/farmacología , Antioxidantes/farmacología , Fármacos Dermatológicos/farmacología , Dilleniaceae/química , Frutas/química , Extractos Vegetales/farmacología , Psoriasis/tratamiento farmacológico , Piel/efectos de los fármacos , Triterpenos/farmacología , Rayos Ultravioleta , Cicatrización de Heridas/efectos de los fármacos , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/normas , Antioxidantes/aislamiento & purificación , Antioxidantes/normas , Biomarcadores/metabolismo , Clobetasol/farmacología , Fármacos Dermatológicos/aislamiento & purificación , Fármacos Dermatológicos/normas , Modelos Animales de Enfermedad , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Triterpenos Pentacíclicos , Fitoterapia , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/normas , Plantas Medicinales , Carbonilación Proteica/efectos de los fármacos , Psoriasis/etiología , Psoriasis/metabolismo , Psoriasis/patología , Ratas Wistar , Piel/metabolismo , Piel/patología , Solventes/química , Factores de Tiempo , Triterpenos/aislamiento & purificación , Triterpenos/normas , Ácido BetulínicoRESUMEN
PURPOSES: The objective of this study was to evaluate the effect of supplementation with vitamin C on intestinal anastomosis healing in malnourished rats. METHODS: Male Wistar rats were divided into three groups: (1) sham, well-nourished rats that received vehicle; (2) FR+Veh, rats that were subjected to food restriction and received vehicle; and (3) FR+VC, rats that were subjected to food restriction and received vitamin C. Four days before surgery, the animals received vitamin C (100 mg/kg/day) via gavage and underwent colon resection with anastomosis in a single plane. The survival rate of rats was monitored until day 7 after surgery. Regarding anastomosis tissues, we examined intra-abdominal adhesion index, hydroxyproline content, collagen density, inflammatory parameters, and oxidative damage to proteins and lipids. RESULTS: Malnutrition decreases body weight and increases mortality; the survival rate was 90 % in group 1, 60 % in group 2, and 80 % in group 3. Vitamin C was able to increase hydroxyproline concentration and density of collagen and decrease the intra-abdominal adhesion index, as well as the infiltration of neutrophils and oxidative damage to proteins in malnourished rats compared to group treated with vehicle. CONCLUSIONS: Preoperative vitamin C supplementation can improve the intestinal anastomosis healing, biochemical alterations, and prolong survival in rats subjected to food restriction.
Asunto(s)
Ácido Ascórbico/uso terapéutico , Colon/cirugía , Suplementos Dietéticos , Desnutrición/tratamiento farmacológico , Cuidados Preoperatorios , Recto/cirugía , Cicatrización de Heridas/efectos de los fármacos , Anastomosis Quirúrgica , Animales , Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/farmacología , Peso Corporal/efectos de los fármacos , Colágeno/metabolismo , Colon/efectos de los fármacos , Colon/patología , Hidroxiprolina/metabolismo , Masculino , Desnutrición/complicaciones , Nitratos/metabolismo , Nitritos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Peroxidasa/metabolismo , Ratas Wistar , Recto/efectos de los fármacos , Recto/patología , Adherencias Tisulares/complicaciones , Adherencias Tisulares/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Sepsis progression is linked to the imbalance between reactive oxygen species and antioxidant enzymes. Sepsis affects multiple organs, but when associated with a chronic inflammatory disease, such as obesity, it may be exacerbated. We hypothesized that obesity could aggravate the oxidative damage to peripheral organs of rats submitted to an animal model of sepsis. Male Wistar rats aged 8 weeks received hypercaloric nutrition for 2 months to induce obesity. Sepsis was induced by cecal ligation and puncture (CLP) procedure, and sham-operated rats were considered as control group. The experimental groups were divided into sham + eutrophic, sham + obese, CLP + eutrophic, and CLP + obese. Twelve and 24 h after surgery, oxidative damage to lipids and proteins and superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in the liver, lung, kidney, and heart. The data indicate that obese rats subjected to sepsis present oxidative stress mainly in the lung and liver. This alteration reflected an oxidative damage to lipids and proteins and an imbalance of SOD and CAT levels, especially 24 h after sepsis. It follows that obesity due to its pro-inflammatory phenotype can aggravate sepsis-induced damage in peripheral organs.
Asunto(s)
Obesidad/complicaciones , Estrés Oxidativo , Sepsis/complicaciones , Animales , Catalasa , Riñón/metabolismo , Hígado/lesiones , Hígado/metabolismo , Pulmón/metabolismo , Lesión Pulmonar/metabolismo , Masculino , Miocardio/metabolismo , Ratas , Ratas Wistar , Superóxido DismutasaRESUMEN
OBJETIVE: The aim of this study was to evaluate the effects of diphenyl diselenide (PhSe)2 and ebselen (EB) in ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) in rats. METHODS: The effects of (PhSe)2 and EB in rats submitted to DSS-induced colitis were determined by measurement of oxidative stress parameters, inflammatory response and bowel histopathological alterations. RESULTS: Animals developed moderate to severe neutrophil infiltration in histopathology assay in DSS rats and (PhSe)2 improved this response. Moreover, the treatment with (PhSe)2 decreased the oxidative damage in lipids and proteins, as well as reversed the superoxide dismutase (SOD) and catalase (CAT) levels in rats treated with DSS. EB was able only to reverse damage in lipids and the low levels of SOD in this animal model. CONCLUSIONS: The organoselenium compounds tested demonstrated an anti-inflammatory and antioxidant activity reducing the colon damage, being (PhSe)2 more effective than EB.
Asunto(s)
Azoles/uso terapéutico , Derivados del Benceno/uso terapéutico , Colitis/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Compuestos de Organoselenio/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Animales , Azoles/farmacología , Derivados del Benceno/farmacología , Catalasa/metabolismo , Colitis/inducido químicamente , Colitis/metabolismo , Colon/efectos de los fármacos , Colon/metabolismo , Modelos Animales de Enfermedad , Inflamación/inducido químicamente , Inflamación/metabolismo , Isoindoles , Masculino , Neutrófilos , Compuestos de Organoselenio/farmacología , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Cecropia glaziovii Sneth leaves extract is widely used as a traditional folk medicine in Brazil, especially for the treatment of diabetes, and as an antihypertensive and antiinflammatory agent. AIM OF THE STUDY: To investigate the anti-inflammatory and antioxidant properties of crude aqueous extract (CAE) of C. glaziovii leaves. MATERIALS AND METHODS: The in vivo anti-inflammatory and antioxidant effect of the CAE (10-300mg/kg, intragastrically) was investigated in the animal model of pleurisy. The cell migration, proinflammatory cytokines (TNF-α, IL-1ß and IL-6), nitrite/nitrate concentration, myeloperoxidase (MPO) activity, oxidative damage in lipids and proteins, lactate dehydrogenase (LDH) activity and total protein content were also analyzed. Furthermore, the in vitro antioxidant activity of CAE was evaluated by the inhibition of formation of thiobarbituric acid reactive substances (TBARS), induced by free radical generators (H2O2, FeSO4 and AAPH) on a lipid-rich substrate. Hence, the chemical characterizarion of CAE by HPLC was therefore performed. The results showed that the inflammatory process caused by the administration of carragenin (Cg) into the pleural cavity resulted in a substantial increase in inflammatory parameters and oxidative damage. These levels seems to be reversed after CAE treatment in animals with similar results to Dexamethasone (Dex) treatment. Further, the CAE was effective in reducing proinflammatory cytokines, cell infiltrate, MPO activity, nitrite/nitrate concentration, LDH activity, and total protein levels with concomitant attenuation of all parameters associated with oxidative damage induced by Cg. Finally, the CAE presented in vitro antioxidant activity induced by free radical generators at all the concentrations investigated. HPLC analysis confirmed the presence of chlorogenic acid and C-glycosylflavonoids (isoorientin and isovitexin) as the major compounds of the CAE. CONCLUSION: CAE of C. glaziovii exerts significant antiinflammatory and antioxidant activities and this effect can be attributed, at least in part, to the presence of chlorogenic acid and the C-glycosylflavonoids.
Asunto(s)
Antiinflamatorios/farmacología , Antioxidantes/farmacología , Cecropia/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Animales , Antiinflamatorios/química , Antioxidantes/química , Carragenina/toxicidad , Dexametasona/farmacología , Masculino , Extractos Vegetales/química , Pleuresia/inducido químicamente , Pleuresia/tratamiento farmacológico , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
Sepsis progression is linked with the imbalance between reactive oxygen species and antioxidant enzymes. Thus, the aim of this study was to evaluate the effect of alpha-lipoic acid (ALA), a powerful antioxidant, in organs of rats submitted to sepsis. Male Wistar rats were subjected to sepsis by cecal ligation puncture (CLP) and treated with ALA or vehicle. After CLP (12 and 24 h), the myeloperoxidase (MPO) activity, protein and lipid oxidative damage, and antioxidant enzymes in the liver, kidney, heart, and lung were evaluated. ALA was effective in reducing MPO activity, lipid peroxidation in the liver, and protein carbonylation only in the kidney in 12 h after CLP. In 12 h, SOD activity increased in the kidney and CAT activity in the liver and kidney with ALA treatment. Thus, ALA was able to reduce the inflammation and oxidative stress in the liver and kidney after sepsis in rats.
Asunto(s)
Antioxidantes/uso terapéutico , Riñón/patología , Hígado/patología , Estrés Oxidativo/efectos de los fármacos , Sepsis/patología , Ácido Tióctico/uso terapéutico , Animales , Catalasa/metabolismo , Ciego/cirugía , Inflamación/tratamiento farmacológico , Riñón/enzimología , Peroxidación de Lípido/efectos de los fármacos , Hígado/enzimología , Pulmón/enzimología , Pulmón/patología , Masculino , Miocardio/enzimología , Miocardio/patología , Infiltración Neutrófila/efectos de los fármacos , Infiltración Neutrófila/inmunología , Peroxidasa/metabolismo , Carbonilación Proteica/efectos de los fármacos , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Sepsis/inmunología , Superóxido Dismutasa/metabolismoRESUMEN
Studies have shown a relationship between diabetes mellitus (DM) and the development of major depressive disorder. Alterations in oxidative stress are associated with the pathophysiology of both diabetes mellitus and major depressive disorder. This study aimed to evaluate the effects of antioxidants N-acetylcysteine and deferoxamine on behaviour and oxidative stress parameters in diabetic rats. To this aim, after induction of diabetes by a single dose of alloxan, Wistar rats were treated with N-acetylcysteine or deferoxamine for 14 days, and then depressive-like behaviour was evaluated. Oxidative stress parameters were assessed in the prefrontal cortex, hippocampus, amygdala, nucleus accumbens and pancreas. Diabetic rats displayed depressive-like behaviour, and treatment with N-acetylcysteine reversed this alteration. Carbonyl protein levels were increased in the prefrontal cortex, hippocampus and pancreas of diabetic rats, and both N-acetylcysteine and deferoxamine reversed these alterations. Lipid damage was increased in the prefrontal cortex, hippocampus, amygdala and pancreas; however, treatment with N-acetylcysteine or deferoxamine reversed lipid damage only in the hippocampus and pancreas. Superoxide dismutase activity was decreased in the amygdala, nucleus accumbens and pancreas of diabetic rats. In diabetic rats, there was a decrease in catalase enzyme activity in the prefrontal cortex, amygdala, nucleus accumbens and pancreas, but an increase in the hippocampus. Treatment with antioxidants did not have an effect on the activity of antioxidant enzymes. In conclusion, animal model of diabetes produced depressive-like behaviour and oxidative stress in the brain and periphery. Treatment with antioxidants could be a viable alternative to treat behavioural and biochemical alterations induced by diabetes.
Asunto(s)
Antioxidantes/farmacología , Encéfalo/efectos de los fármacos , Trastorno Depresivo/prevención & control , Diabetes Mellitus Experimental/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Páncreas/efectos de los fármacos , Acetilcisteína/farmacología , Animales , Conducta Animal/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Deferoxamina/farmacología , Trastorno Depresivo/metabolismo , Trastorno Depresivo/patología , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Experimental/psicología , Depuradores de Radicales Libres/farmacología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Páncreas/metabolismo , Páncreas/patología , Ratas , Ratas Wistar , Sideróforos/farmacologíaRESUMEN
AIMS: The aim of this study was to investigate the effect of subchronic administration of agomelatine on energy metabolism, oxidative stress markers and antioxidant defense in the brains of rats. METHODS: The animals received daily intraperitoneal injections of agomelatine (10, 30 or 50 mg/kg) or saline for 14 days. The prefrontal cortex, cerebellum, hippocampus, striatum and posterior cortex were analyzed. RESULTS: The findings showed that complex I was activated in the prefrontal cortex, cerebellum and striatum and inhibited in the posterior cortex at the 10-mg/kg dose, and inhibited in all brain areas analyzed at the 30-mg/kg and 50-mg/kg doses. Complex II was activated in the posterior cortex at the 50-mg/kg dose. Complex IV was inhibited in the striatum and posterior cortex at the 10-mg/kg dose, inhibited in the striatum at the 30-mg/kg dose and activated in the hippocampus at the 50-mg/kg dose. Creatine kinase activity was inhibited in the striatum at the 10-mg/kg and 30-mg/kg doses. Lipid peroxidation and protein carbonylation levels were not changed after the administration of agomelatine. Superoxide dismutase activity was increased in the striatum at the 10-mg/kg dose, and catalase activity was inhibited in the cerebellum at the 10-mg/kg dose and increased in the posterior cortex at the 30-mg/kg dose. CONCLUSIONS: Our results are consistent with other studies showing that some antidepressants may influence brain energy metabolism and oxidative stress parameters and expand knowledge about the effects of agomelatine in biochemical parameters in the brains of rats.
Asunto(s)
Acetamidas/farmacología , Antidepresivos/farmacología , Encéfalo/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Acetamidas/administración & dosificación , Animales , Antidepresivos/administración & dosificación , Masculino , Ratas , Ratas WistarRESUMEN
Ketamine, an antagonist of N-methyl-d-aspartate receptors, has produced rapid antidepressant effects in patients with depression, as well as in animal models. However, the extent and duration of the antidepressant effect over longer periods of time has not been considered. This study evaluated the effects of single dose of ketamine on behavior and oxidative stress, which is related to depression, in the brains of adult rats subjected to maternal deprivation. Deprived and nondeprived Wistar rats were divided into four groups nondeprived+saline; nondeprived+S-ketamine (15 mg/kg); deprived+saline; deprived+S-ketamine (15 mg/kg). A single dose of ketamine or saline was administrated during the adult phase, and 14 days later depressive-like behavior was assessed. In addition, lipid damage, protein damage, and antioxidant enzyme activities were evaluated in the rat brain. Maternal deprivation induces a depressive-like behavior, as verified by an increase in immobility and anhedonic behavior. However, a single dose of ketamine was able to reverse these alterations, showing long-term antidepressant effects. The brains of maternally deprived rats had an increase in protein oxidative damage and lipid peroxidation, but administration of a single dose of ketamine reversed this damage. The activities of antioxidant enzymes superoxide dismutase and catalase were reduced in the deprived rat brains. However, ketamine was also able to reverse these changes. In conclusion, these findings indicate that a single dose of ketamine is able to induce long-term antidepressant effects and protect against neural damage caused by oxidative stress in adulthood rats following maternal deprivation.
Asunto(s)
Antidepresivos/administración & dosificación , Encéfalo/efectos de los fármacos , Trastorno Depresivo/tratamiento farmacológico , Ketamina/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Anhedonia/efectos de los fármacos , Anhedonia/fisiología , Animales , Encéfalo/fisiopatología , Catalasa/metabolismo , Trastorno Depresivo/fisiopatología , Modelos Animales de Enfermedad , Peroxidación de Lípido/efectos de los fármacos , Peroxidación de Lípido/fisiología , Masculino , Privación Materna , Estrés Oxidativo/fisiología , Ratas Wistar , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/fisiopatología , Superóxido Dismutasa/metabolismoRESUMEN
Sepsis is a severe clinical syndrome in which a system-wide inflammatory response follows initial attempts to eliminate pathogens. It is not novel that in sepsis the brain is one of the first organs affected which causes an increase in morbidity and mortality and its consequences may be exacerbated when associated with a diagnosis of chronic inflammation, such as in obesity. Thus, the aim of the present study is to evaluate the susceptibility to brain damage after sepsis in obese rats. During two months, Wistar rats, 60 days, 250-300g received hypercaloric nutrition to induce obesity. Sepsis was submitted to the cecal ligation and perforation (CLP) procedure and sham-operated rats was considered control group. The experimental groups were divided into Sham + Eutrophic, Sham + Obesity, CLP + Eutrophic and CLP + Obesity. Twelve and twenty four hours after surgery the blood brain barrier (BBB) permeability, nitrite/nitrate concentration, myeloperoxidase (MPO) activity, oxidative damage to lipids and proteins and superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in the hippocampus, cortex and prefrontal cortex. The data indicate that in obese rats subjected to sepsis occurs an increase of BBB permeability in different brain regions compared to eutrophic septic rats. This alteration reflected an increase of MPO activity, concentration of nitrite/nitrate, oxidative damage to lipids and proteins and an imbalance of SOD and CAT especially 24 hours after sepsis. It follows that obesity due to its pro-inflammatory phenotype can aggravate or accelerate the sepsis-induced damage in rat brain.