RESUMO
Oral tolerance blocks the development of specific immune responses to proteins ingested by the oral route. One of the first registries of oral tolerance showed that guinea pigs fed corn became refractory to hypersensitivity to corn proteins. Mice fed with chow containing corn are tolerant to zein, and parenteral injection of zein plus adjuvant blocks immunization to unrelated proteins injected concomitantly and reduces unspecific inflammation. Extensive and prolonged inflammatory infiltrate in the wound bed is one of the causes of pathological wound healing. Previous research shows that intraperitoneal injection of zein concomitant with skin injuries reduces the inflammatory infiltrate in the wound bed and improves wound healing. Herein, we tested if one subcutaneous injection of zein before skin injury improves wound healing. We also investigated how long the effects triggered by zein could improve skin wound healing. Mice fed zein received two excisional wounds on the interscapular skin under anesthesia. Zein plus Al(OH)3 was injected at the tail base at 10 min, or 3, 5, or 7 days before skin injuries. Wound healing was analyzed at days 7 and 40 after injury. Our results showed that a zein injection up to 5 days before skin injury reduced the inflammatory infiltrate, increased the number of T-cells in the wound bed, and improved the pattern of collagen deposition in the neodermis. These findings could promote the development of new strategies for the treatment and prevention of pathological healing using proteins normally found in the common diet.
Assuntos
Pele , Cicatrização , Animais , Colágeno , Cobaias , Injeções Intraperitoneais , Injeções Subcutâneas , CamundongosRESUMO
The effects of exercise training on oxidative stress in gastrocnemius of rats with pulmonary hypertension were studied. Four groups were established: sedentary control (SC), sedentary monocrotaline (SM), trained control (TC), trained monocrotaline (TM). Exercise was applied for 4 weeks, 5 days/week, 50-60 min/session, at 60% of VO2 max. Right ventricular (RV) pressures were measured, heart and gastrocnemius were removed for morphometric/biochemical analysis. Lipid peroxidation (LPO), H2O2, GSH/GSSG, and activity/expression of antioxidant enzymes were evaluated. Increased RV hypertrophy, systolic and end-diastolic pressures (RVEDP) were observed in SM animals, and the RVEDP was decreased in TM vs. SM. H2O2, SOD-1, and LPO were higher in the SM group than in SC. In TM, H2O2 was further increased when compared to SM, with a rise in antioxidant defences and a decrease in LPO. GSH/GSSG was higher only in the TC group. Exercise induced an efficient antioxidant adaptation, preventing oxidative damage to lipids.
Assuntos
Monocrotalina , Hipertensão Arterial Pulmonar , Animais , Antioxidantes/metabolismo , Dissulfeto de Glutationa/metabolismo , Peróxido de Hidrogênio/metabolismo , Lipídeos , Monocrotalina/metabolismo , Monocrotalina/toxicidade , Músculo Esquelético , Estresse Oxidativo , Ratos , Ratos WistarRESUMO
Oral tolerance blocks the development of specific immune responses to proteins ingested by the oral route. One of the first registries of oral tolerance showed that guinea pigs fed corn became refractory to hypersensitivity to corn proteins. Mice fed with chow containing corn are tolerant to zein, and parenteral injection of zein plus adjuvant blocks immunization to unrelated proteins injected concomitantly and reduces unspecific inflammation. Extensive and prolonged inflammatory infiltrate in the wound bed is one of the causes of pathological wound healing. Previous research shows that intraperitoneal injection of zein concomitant with skin injuries reduces the inflammatory infiltrate in the wound bed and improves wound healing. Herein, we tested if one subcutaneous injection of zein before skin injury improves wound healing. We also investigated how long the effects triggered by zein could improve skin wound healing. Mice fed zein received two excisional wounds on the interscapular skin under anesthesia. Zein plus Al(OH)3 was injected at the tail base at 10 min, or 3, 5, or 7 days before skin injuries. Wound healing was analyzed at days 7 and 40 after injury. Our results showed that a zein injection up to 5 days before skin injury reduced the inflammatory infiltrate, increased the number of T-cells in the wound bed, and improved the pattern of collagen deposition in the neodermis. These findings could promote the development of new strategies for the treatment and prevention of pathological healing using proteins normally found in the common diet.
RESUMO
Through alteration of wave-generating atmospheric systems, global climate changes play a fundamental role in regional wave climate. However, long-term wave-climate cycles and their associated forcing mechanisms remain poorly constrained, in part due to a relative dearth of highly resolved archives. Here we use the morphology of former shorelines preserved in beach-foredune ridges (BFR) within a protected embayment to reconstruct changes in predominant wave directions in the Subtropical South Atlantic during the last ~ 3000 years. These analyses reveal multi-centennial cycles of oscillation in predominant wave direction in accordance with stronger (weaker) South Atlantic mid- to high-latitudes mean sea-level pressure gradient and zonal westerly winds, favouring wave generation zones in higher (lower) latitudes and consequent southerly (easterly) wave components. We identify the Southern Annular Mode as the primary climate driver responsible for these changes. Long-term variations in interhemispheric surface temperature anomalies coexist with oscillations in wave direction, which indicates the influence of temperature-driven atmospheric teleconnections on wave-generation cycles. These results provide a novel geomorphic proxy for paleoenvironmental reconstructions and present new insights into the role of global multi-decadal to multi-centennial climate variability in controlling coastal-ocean wave climate.
RESUMO
Lysosomal storage disorders (LSDs) are diseases characterized by the accumulation of macromolecules in the late endocytic system and are caused by inherited defects in genes that encode mainly lysosomal enzymes or transmembrane lysosomal proteins. Niemann-Pick type C disease (NPCD), a LSD characterized by liver damage and progressive neurodegeneration that leads to early death, is caused by mutations in the genes encoding the NPC1 or NPC2 proteins. Both proteins are involved in the transport of cholesterol from the late endosomal compartment to the rest of the cell. Loss of function of these proteins causes primary cholesterol accumulation, and secondary accumulation of other lipids, such as sphingolipids, in lysosomes. Despite years of studying the genetic and molecular bases of NPCD and related-lysosomal disorders, the pathogenic mechanisms involved in these diseases are not fully understood. In this review we will summarize the pathogenic mechanisms described for NPCD and we will discuss their relevance for other LSDs with neurological components such as Niemann- Pick type A and Gaucher diseases. We will particularly focus on the activation of signaling pathways that may be common to these three pathologies with emphasis on how the intra-lysosomal accumulation of lipids leads to pathology, specifically to neurological impairments. We will show that although the primary lipid storage defect is different in these three LSDs, there is a similar secondary accumulation of metabolites and activation of signaling pathways that can lead to common pathogenic mechanisms. This analysis might help to delineate common pathological mechanisms and therapeutic targets for lysosomal storage diseases.
Assuntos
Doença de Gaucher/metabolismo , Metabolismo dos Lipídeos/genética , Lisossomos/patologia , Doença de Niemann-Pick Tipo A/metabolismo , Doença de Niemann-Pick Tipo C/metabolismo , Encéfalo/citologia , Encéfalo/metabolismo , Encéfalo/patologia , Colesterol/metabolismo , Doença de Gaucher/genética , Doença de Gaucher/patologia , Glucosilceramidase/genética , Glucosilceramidase/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Lisossomos/metabolismo , Mutação , Neurônios/citologia , Neurônios/metabolismo , Neurônios/patologia , Proteína C1 de Niemann-Pick , Doença de Niemann-Pick Tipo A/genética , Doença de Niemann-Pick Tipo A/patologia , Doença de Niemann-Pick Tipo C/genética , Doença de Niemann-Pick Tipo C/patologia , Transdução de Sinais/genética , Esfingolipídeos/metabolismo , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismoRESUMO
Establishing new animal models for the study of inflammation is very important in the process of discovering new drugs, since the inflammatory event is the basis of many pathological processes. Whereas rodent models have been the primary focus of inflammation research, we defend the zebrafish (Danio rerio) test as a feasible alternative for preclinical studies. Moreover, despite all the technological development already achieved by humanity, nature can still be considered a relevant source of new medicines. In this context, the aim of this work was to evaluate the anti-inflammatory effect of a substance isolated from the medicinal plant Annona crassilfora Mart, the peltatoside, in an inflammatory model of zebrafish. It was determined: (i) total leukocyte count in the coelomate exudate; (ii) N-acetyl-ß-d-glucuronidase (NAG); (iii) myeloperoxidase (MPO); (iv) and the histology of liver, intestine and mesentery. Peltotoside (25, 50 and 100 µg) and dexamethasone (25 µg) were administered intracelomatically (i.c.) 30 min before carrageenan (i.c.). Pretreatment with peltatoside at three doses significantly inhibited leukocyte recruitment in the coelomic cavity, and inhibited NAG and MPO activity against the action of Cg, in a similar manner as dexamethasone. However, some microlesions in the evaluated organs were detected. The dose of 25 µg showed an anti-inflammatory effect with lower undesirable effects in the tissues. Our results suggest that the zebrafish test was satisfactory in performing our analyzes and that the peltotoside has a modulatory action in reducing leukocyte migration.
Assuntos
Annona/química , Anti-Inflamatórios/farmacologia , Modelos Animais de Doenças , Glicosídeos/farmacologia , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Quercetina/análogos & derivados , Peixe-Zebra , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Glicosídeos/administração & dosagem , Glicosídeos/química , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Folhas de Planta/química , Plantas Medicinais/química , Quercetina/administração & dosagem , Quercetina/química , Quercetina/farmacologiaRESUMO
This study investigated the impact of experimental pulmonary arterial hypertension (PAH) progression by evaluating morphometric and functional parameters, oxidative stress, autonomic nervous system (ANS) activation, and inflammation in the right (RV) and left (LV) ventricles. Male rats were first divided into two groups: monocrotaline (MCT) and control. The MCT group received a single MCT injection (60 mg/kg, intraperitoneal), while control received saline. The MCT and control groups were further divided into four cohorts based on how long they were observed: 1, 2, 3, and 4 weeks. Animals were submitted to echocardiographic and hemodynamic analysis. RV and LV were used for morphometric, biochemical, and histological measurements. Autonomic modulation was evaluated by cardiac spectral analysis, considering two components: low frequency (LF) and high frequency (HF). Lung and liver weight was used for morphometric analysis. MCT induced 100% mortality at 4 weeks. In the RV, disease progression led to mild inflammation and enhanced reactive oxygen species (ROS) in week 1, followed by moderate inflammation, ROS production, and hypertrophy in week 2. By week 3, there was moderate inflammation, oxidative stress, and ANS imbalance, with development of right heart dysfunction. LV biochemical changes and inflammation were observed at week 3. The initial changes appeared to be related to inflammation and ROS, and the later ones to inflammation, oxidative stress, and ANS imbalance in MCT animals. This study reinforces the severity of the disease in the RV, the late effects in the LV, and the role of ANS imbalance in the development of heart dysfunction.
Assuntos
Sistema Nervoso Autônomo , Hipertensão Pulmonar , Estresse Oxidativo , Remodelação Ventricular , Animais , Sistema Nervoso Autônomo/metabolismo , Sistema Nervoso Autônomo/patologia , Sistema Nervoso Autônomo/fisiopatologia , Modelos Animais de Doenças , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Inflamação/metabolismo , Inflamação/patologia , Inflamação/fisiopatologia , Masculino , Ratos , Ratos WistarRESUMO
This study was designed to investigate the effect of pterostilbene (PTS) on cardiac oxidative stress in vitro, as this is a simple and promising methodology to study cardiac disease. Cardiac myoblasts (H9c2 cells) and homogenised cardiac tissue were incubated with the PTS and cyclodextrin (PTS + HPßCD) complex for 1 and 24 h, respectively, at concentrations of 50µM for the cells and 25 and 50µM for cardiac tissue. The PTS + HPßCD complex was used to increase the solubility of PTS in water. After the pretreatment period, cardiomyoblasts were challenged with hydrogen peroxide (6.67µM) for 10 min, while cardiac tissue was submitted to a hydroxyl radical generator system (30 min). Cellular viability, oxidative stress biomarkers (e.g. total reactive oxygen species (ROS), carbonyl assay and lipoperoxidation) and the antioxidant response (e.g. sulfhydryl and the antioxidant enzyme activities of superoxide dismutase, catalase and glutathione peroxidase) were evaluated. In cardiomyoblasts, the PTS + HPßCD complex (50µM) increased cellular viability. Moreover, the PTS + HPßCD complex also significantly increased sulfhydryl levels in the cells submitted to an oxidative challenge. In cardiac tissue, lipid peroxidation, carbonyls and ROS levels were significantly increased in the groups submitted to oxidative damage, while the PTS + HPßCD complex significantly reduced ROS levels in these groups. In addition, the PTS + HPßCD complex also provoked increased catalase activity in both experimental protocols. These data suggest that the PTS + HPßCD complex may play a cardioprotective role through a reduction of ROS levels associated with an improved antioxidant response.
Assuntos
Antioxidantes/farmacologia , Coração/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Mioblastos Cardíacos/efeitos dos fármacos , Estilbenos/farmacologia , Animais , Antioxidantes/química , Apoptose/efeitos dos fármacos , Catalase/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Ciclodextrinas/química , Glutationa Peroxidase/metabolismo , Homeostase/fisiologia , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Mioblastos Cardíacos/citologia , Mioblastos Cardíacos/metabolismo , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Oxirredução , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Estilbenos/química , Superóxido Dismutase/metabolismoRESUMO
Vitamin E (vit. E) and vitamin C (vit. C) are antioxidants that inhibit nociception. The effect of these vitamins on oxidative-stress markers in the spinal cord of rats with chronic constriction injury (CCI) of the sciatic nerve is unknown. This study investigated the effect of intraperitoneal administration of vit. E (15 mg·kg-1·day-1) and vit. C (30 mg·kg-1·day-1), given alone or in combination, on spinal cord oxidative-stress markers in CCI rats. Adult male Wistar rats weighing 200-250 g were divided equally into the following groups: Naive (rats did not undergo surgical manipulation); Sham (rats in which all surgical procedures involved in CCI were used except the ligature), and CCI (rats in which four ligatures were tied loosely around the right common sciatic nerve), which received injections of vitamins or vehicle (saline containing 1% Tween 80) for 3 or 10 days (n=6/each group). The vitamins prevented the reduction in total thiol content and the increase in superoxide-anion generation that were found in vehicle-treated CCI rats. While nitric-oxide metabolites increased in vehicle-treated CCI rats 3 days after surgery, these metabolites did not show significant changes in vitamin-treated CCI rats. In all rats, total antioxidant capacity and hydrogen-peroxide levels did not change significantly. Lipid hydroperoxides increased 25% only in vehicle-treated CCI rats. These changes may contribute to vit. C- and vit. E-induced antinociception, because scavenging reactive oxygen species seems to help normalize the spinal cord oxidative status altered by pain.
Assuntos
Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Neuropatia Ciática/tratamento farmacológico , Medula Espinal/efeitos dos fármacos , alfa-Tocoferol/uso terapêutico , Animais , Biomarcadores/metabolismo , Modelos Animais de Doenças , Masculino , Medição da Dor , Limiar da Dor/efeitos dos fármacos , Ratos , Ratos Wistar , Neuropatia Ciática/metabolismo , Medula Espinal/metabolismoRESUMO
Several works have shown that triterpenes induce peripheral antinociception by activation of cannabinoid receptors and endocannabinoids; besides, several research groups have reported activation of cannabinoid receptors in peripheral antinociception. The aim of this study was to assess the involvement of the cannabinoid system in the antinociceptive effect induced by tingenone against hyperalgesia evoked by prostaglandin E2 (PGE2) at peripheral level. The paw pressure test was used and the hyperalgesia was induced by intraplantar injection of PGE2 (2 µg/paw). All drugs were injected subcutaneously in the hind paws of male Swiss mice. Tingenone (200 µg/paw) administered into the right hind paw induced a local antinociceptive effect, that was antagonized by AM630, a selective antagonist to CB2 cannabinoid receptor. AM251, a selective antagonist to CB1 cannabinoid receptor, did not alter the peripheral antinociceptive effect of tingenone. MAFP, a fatty acid amide hydrolase (FAAH) inhibitor; VDM11, an anandamide reuptake inhibitor; and JZL184, monoacylglycerol lipase (MAGL) inhibitor did not potentiate the peripheral antinociceptive effect of the lower dose of tingenone (50 µg/paw). The results suggest that tingenone induced a peripheral antinociceptive effect via cannabinoid receptor activation. Therefore, this study suggests a pharmacological potential for a new analgesic drug.
Assuntos
Analgésicos/farmacologia , Agonistas de Receptores de Canabinoides/farmacologia , Triterpenos Pentacíclicos/farmacologia , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/metabolismo , Triterpenos/farmacologia , Amidoidrolases , Animais , Ácidos Araquidônicos/metabolismo , Ácidos Araquidônicos/farmacologia , Benzodioxóis/farmacologia , Canabinoides/metabolismo , Endocanabinoides/metabolismo , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Indóis/farmacologia , Masculino , Camundongos , Monoacilglicerol Lipases/metabolismo , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/metabolismo , Pirazóis/farmacologiaRESUMO
Vitamin E (vit. E) and vitamin C (vit. C) are antioxidants that inhibit nociception. The effect of these vitamins on oxidative-stress markers in the spinal cord of rats with chronic constriction injury (CCI) of the sciatic nerve is unknown. This study investigated the effect of intraperitoneal administration of vit. E (15 mg·kg-1·day-1) and vit. C (30 mg·kg-1·day-1), given alone or in combination, on spinal cord oxidative-stress markers in CCI rats. Adult male Wistar rats weighing 200-250 g were divided equally into the following groups: Naive (rats did not undergo surgical manipulation); Sham (rats in which all surgical procedures involved in CCI were used except the ligature), and CCI (rats in which four ligatures were tied loosely around the right common sciatic nerve), which received injections of vitamins or vehicle (saline containing 1% Tween 80) for 3 or 10 days (n=6/each group). The vitamins prevented the reduction in total thiol content and the increase in superoxide-anion generation that were found in vehicle-treated CCI rats. While nitric-oxide metabolites increased in vehicle-treated CCI rats 3 days after surgery, these metabolites did not show significant changes in vitamin-treated CCI rats. In all rats, total antioxidant capacity and hydrogen-peroxide levels did not change significantly. Lipid hydroperoxides increased 25% only in vehicle-treated CCI rats. These changes may contribute to vit. C- and vit. E-induced antinociception, because scavenging reactive oxygen species seems to help normalize the spinal cord oxidative status altered by pain.
Assuntos
Animais , Masculino , Ratos , alfa-Tocoferol/uso terapêutico , Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Neuropatia Ciática/tratamento farmacológico , Medula Espinal/efeitos dos fármacos , Biomarcadores/metabolismo , Modelos Animais de Doenças , Medição da Dor , Limiar da Dor/efeitos dos fármacos , Ratos Wistar , Neuropatia Ciática/metabolismo , Medula Espinal/metabolismoRESUMO
Byrsonima verbascifolia (Malpighiaceae), commonly known as 'murici', is used in folk medicine, for example, in the treatment of inflammation. The anti-inflammatory activity of the butanolic fraction of B. verbascifolia leaves (BvBF) was previously reported by our group, and the present study was designed to evaluate their antinociceptive effects. BvBF (25, 50, and 100 mg/kg) administered intraperitoneally (i.p.) inhibited acetic acid induced abdominal writhing. In the formalin test, BvBF (10, 30 and 100 mg/kg, i.p.) caused a reduction in licking time in both the neurogenic and inflammatory phases. Moreover, we demonstrated that BvBF (30 and 100 mg/kg, i.p.) caused an increase in the latency to response in the hot-plate test. These results demonstrate that BvBF possesses marked peripheral and central antinociceptive activities. Pre-treatment with the non-selective receptor antagonist naloxone (5 mg/kg, i.p.) abolished the antinociceptive effects of BvBF (100 mg/kg, i.p.) in the neurogenic phase of the formalin and hot-plate tests. The anti-inflammatory activity of BvBF (previously reported) as well as the participation of the opioidergic system seems to be responsible, at least in part, for these antinociceptive effects. Finally, BvBF at the doses investigated (25, 50 and 100 mg/Kg) did not cause any toxicity signals, showing that the antinociceptive activity is devoid of sedative and hypomotility effects.
Assuntos
Analgésicos/farmacologia , Malpighiaceae , Nociceptividade/efeitos dos fármacos , Medição da Dor/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta , Analgésicos/isolamento & purificação , Animais , Butanóis/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Masculino , Camundongos , Nociceptividade/fisiologia , Medição da Dor/métodos , Extratos Vegetais/isolamento & purificaçãoRESUMO
Hyperhomocysteinemia (HHcy) is associated with cardiovascular disease, atherosclerosis and reactive oxygen species generation. Thus, our aim was to investigate whether there was an association between HHcy, blood pressure, autonomic control and liver oxidative stress. Male Wistar rats were divided into 2 groups and treated for 8weeks: one group (control, CO) received tap water, while the other group (methionine, ME) was given a 100mg/kg of methionine in water by gavage. Two catheters were implanted into the femoral artery and vein to record arterial pressure (AP) and heart rate (HR) and drug administration. Signals were recorded by a data acquisition system. Baroreflex sensitivity was evaluated by HR responses to AP changes induced by vasoactive drugs. HR variability and AP variability were performed by spectral analysis in time and frequency domains to evaluate the contribution of the sympathetic and parasympathetic modulation. Lipid peroxidation and antioxidant enzyme activities were evaluated by measuring superoxide dismutase, catalase and glutathione peroxidase in liver homogenates. The ME group presented a significant increase in systolic arterial pressure (118±9 vs 135±6mmHg), diastolic arterial pressure (81±6 vs. 92±4) and mean arterial pressure (95±7 vs. 106±6). In addition, pulse interval variability presented a significant decrease (41%), while the low frequency component of AP was significantly increased (delta P=6.24mmHg(2)) in the ME group. We also found a positive association between lipid peroxidation and cardiac sympathetic modulation, sympathetic and vagal modulation ratio and systolic pressure variability. Collectively, these findings showed that HHcy induced dysfunction of cardiovascular autonomic system and liver oxidative stress.
Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Sistema Cardiovascular/fisiopatologia , Hiper-Homocisteinemia/fisiopatologia , Hipertensão/etiologia , Fígado/metabolismo , Estresse Oxidativo , Animais , Sistema Nervoso Autônomo/efeitos dos fármacos , Barorreflexo/efeitos dos fármacos , Barorreflexo/fisiologia , Sistema Cardiovascular/efeitos dos fármacos , Catalase/análise , Glutationa Peroxidase/análise , Sistema de Condução Cardíaco/efeitos dos fármacos , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Hiper-Homocisteinemia/induzido quimicamente , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/metabolismo , Hipertensão/fisiopatologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Metionina/toxicidade , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/análiseRESUMO
This study tested the hypothesis that simvastatin treatment can improve cardiovascular and autonomic functions and membrane lipoperoxidation, with an increased effect when applied to physically trained ovariectomized rats. Ovariectomized rats were divided into sedentary, sedentary+simvastatin and trained+simvastatin groups (n = 8 each). Exercise training was performed on a treadmill for 8 weeks and simvastatin (5â mg/kg) was administered in the last 2 weeks. Blood pressure (BP) was recorded in conscious animals. Baroreflex sensitivity was evaluated by the tachycardic and bradycardic responses to BP changes. Cardiac vagal and sympathetic effects were determined using methylatropine and propranolol. Oxidative stress was evaluated based on heart and liver lipoperoxidation using the chemiluminescence method. The simvastatin-treated groups presented reduced body weight and mean BP (trained+simvastatin = 99 ± 2 and sedentary+simvastatin = 107 ± 2â mmHg) compared to the sedentary group (122 ± 1â mmHg). Furthermore, the trained group showed lower BP and heart rate compared to the other groups. Tachycardic and bradycardic responses were enhanced in both simvastatin-treated groups. The vagal effect was increased in the trained+simvastatin group and the sympathetic effect was decreased in the sedentary+simvastatin group. Hepatic lipoperoxidation was reduced in sedentary+simvastatin (≈21%) and trained+simvastatin groups (≈57%) compared to the sedentary group. Correlation analysis involving all animals demonstrated that cardiac lipoperoxidation was negatively related to the vagal effect (r = -0.7) and positively correlated to the sympathetic effect (r = 0.7). In conclusion, improvement in cardiovascular and autonomic functions associated with a reduction of lipoperoxidation with simvastatin treatment was increased in trained ovariectomized rats.
Assuntos
Sistema Nervoso Autônomo/efeitos dos fármacos , Barorreflexo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipolipemiantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Sinvastatina/farmacologia , Animais , Sistema Nervoso Autônomo/fisiologia , Feminino , Luminescência , Ovariectomia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Condicionamento Físico Animal , Ratos , Treinamento ResistidoRESUMO
This study tested the hypothesis that simvastatin treatment can improve cardiovascular and autonomic functions and membrane lipoperoxidation, with an increased effect when applied to physically trained ovariectomized rats. Ovariectomized rats were divided into sedentary, sedentary+simvastatin and trained+simvastatin groups (n = 8 each). Exercise training was performed on a treadmill for 8 weeks and simvastatin (5 mg/kg) was administered in the last 2 weeks. Blood pressure (BP) was recorded in conscious animals. Baroreflex sensitivity was evaluated by the tachycardic and bradycardic responses to BP changes. Cardiac vagal and sympathetic effects were determined using methylatropine and propranolol. Oxidative stress was evaluated based on heart and liver lipoperoxidation using the chemiluminescence method. The simvastatin-treated groups presented reduced body weight and mean BP (trained+simvastatin = 99 ± 2 and sedentary+simvastatin = 107 ± 2 mmHg) compared to the sedentary group (122 ± 1 mmHg). Furthermore, the trained group showed lower BP and heart rate compared to the other groups. Tachycardic and bradycardic responses were enhanced in both simvastatin-treated groups. The vagal effect was increased in the trained+simvastatin group and the sympathetic effect was decreased in the sedentary+simvastatin group. Hepatic lipoperoxidation was reduced in sedentary+simvastatin (≈21%) and trained+simvastatin groups (≈57%) compared to the sedentary group. Correlation analysis involving all animals demonstrated that cardiac lipoperoxidation was negatively related to the vagal effect (r = -0.7) and positively correlated to the sympathetic effect (r = 0.7). In conclusion, improvement in cardiovascular and autonomic functions associated with a reduction of lipoperoxidation with simvastatin treatment was increased in trained ovariectomized rats.
Assuntos
Animais , Feminino , Ratos , Sistema Nervoso Autônomo/efeitos dos fármacos , Barorreflexo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipolipemiantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Sinvastatina/farmacologia , Sistema Nervoso Autônomo/fisiologia , Luminescência , Ovariectomia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Condicionamento Físico Animal , Treinamento ResistidoRESUMO
The objective of this study was to explore the influence of the renin-angiotensin system on cardiac prooxidants and antioxidants levels and its association to autonomic imbalance induced by hyperthyroidism. Male Wistar rats were divided into four groups: control, losartan (10mg/kg/day by gavage, 28 day), thyroxine (T4) (12 mg/L in drinking water for 28 days), and T4+losartan. Spectral analysis (autonomic balance), angiotensin II receptor (AT1R), NADPH oxidase, Nrf2 and heme-oxygenase-1 (HO-1) myocardial protein expression, and hydrogen peroxide (H2O2) concentration were quantified. Autonomic imbalance induced by hyperthyroidism (~770%) was attenuated in the T4+losartan group (~32%) (P<0.05). AT1R, NADPH oxidase, H2O2, as well as concentration, Nrf2 and HO-1 protein expression were elevated (~172%, 43%, 40%, 133%, and 154%, respectively) in T4 group (P<0.05). H2O2 and HO-1 levels were returned to control values in the T4+losartan group (P<0.05). The overall results demonstrate a positive impact of RAS blockade in the autonomic control of heart rate, which was associated with an attenuation of H2O2 levels, as well as with a reduced counter-regulatory response of HO-1 in experimental hyperthyroidism.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Hipertireoidismo/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptor Tipo 1 de Angiotensina/fisiologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Animais , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Hipertireoidismo/tratamento farmacológico , Masculino , Ratos , Ratos WistarRESUMO
Sexual dichromatism and sexual dimorphism of body size are reasonably well studied in butterflies. Sexual size dimorphism of color pattern elements, however, is much less explored. The object of this study is Heliconius, a genus of butterflies well known for the coevolution between mate color preferences and mimicry. Given the sexual role of wing coloration, we investigated the existence of sexual size dimorphism in the wing color elements of a mimetic pair-Heliconius erato phyllis Fabricius and Heliconius besckei Ménétriés-and analyzed the allometric patterns of these traits. Correlation between size of elements in the dorsal and ventral wing surfaces were also estimated. In both species, three out of four elements were larger in males, but the non-dimorphic element was not the same. With regard to the allometric patterns, our most important finding was that smaller males of one species have proportionally larger yellow bars. This is the first study specifically concerning quantitative sexual dimorphism in the coloration of this well-known genus of butterflies and it opens new prospects to investigate sex-related natural selection and sexual selection of color pattern elements.
Assuntos
Borboletas , Cor , Caracteres Sexuais , Asas de Animais , Animais , Feminino , Masculino , FenótipoRESUMO
BACKGROUND/AIMS: The activation of proteinase-activated receptors (PARs) has been implicated in the development of important hallmarks of inflammation, including in vivo leukocyte recruitment. Here, we examined the effects of aprotinin, a potent inhibitor of trypsin proteinase and the kallikrein-kinin system, and the PAR-4 antagonist YPGKF-NH(2) (tcY-NH(2)) on neutrophil recruitment in response to carrageenan and trypsin in the pleural cavity of mice. METHODS: BALB/c mice were intrapleurally injected with trypsin or PAR-4-activating peptide AY-NH(2), pretreated with aprotinin or tcY-NH(2) (1 µg/cavity) prior to an intrapleural injection of trypsin or carrageenan, or pretreated with leukotriene B(4) antagonist U-75302 (3 µg/cavity) prior to a trypsin injection. The number of infiltrating neutrophils was evaluated after 4 h. RESULTS: PAR-4-activating peptide AY-NH(2) and trypsin-induced neutrophil recruitment was inhibited by aprotinin, tcY-NH(2) or U-75302. Aprotinin and tcY-NH(2) also inhibited neutrophil recruitment induced by carrageenan. CONCLUSION: These data suggest a key role for PAR-4 in mediating neutrophil recruitment in a mouse model of pleurisy induced by the activity of trypsin or trypsin-like enzymes.
Assuntos
Neutrófilos/imunologia , Pleurisia/imunologia , Receptores Ativados por Proteinase/imunologia , Animais , Aprotinina/farmacologia , Carragenina , Movimento Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/efeitos dos fármacos , Oligopeptídeos/farmacologia , Pleurisia/induzido quimicamente , Receptores Ativados por Proteinase/antagonistas & inibidores , Tripsina , Inibidores da Tripsina/farmacologiaRESUMO
Pulmonary arterial hypertension (PAH) is a disease that increases the pulmonary vascular resistance, causing hypertrophy and subsequent right heart failure. Oxidative stress is involved in the pathogenesis of PAH, and estrogen is considered an antioxidant. Thus, the aim of this study was to test the hypothesis that estrogen could attenuate PAH by modulating oxidative stress. Female Wistar rats were ovariectomized or suffered the surgery simulation (sham). After 7 days, subcutaneous pellets with 17ß-estradiol or sunflower oil were implanted. At this time, PAH was induced by means of a single dose of monocrotaline (MCT) (60 mg·kg(-1) i.p.). The experimental groups were as follows: (1) sham, (2) sham + MCT, (3) ovariectomy (O), (4) ovariectomy + MCT (OM), (5) ovariectomy + estrogen replacement + MCT (ORM). Hemodynamic measurements were performed 21 days after MCT or saline. Nonovariectomized animals were assessed in the stage of diestrus. Afterwards, the rats were killed to collect the heart, the lung and the liver to evaluate morphometry. Samples of the right ventricle were used to analyse the reduced glutathione : oxidized glutathione ratio. Lung congestion in the OM group, which was decreased in the ORM group, was observed. Right ventricle end-diastolic pressure was increased in the OM and the ORM groups. The glutathione ratio decreased in the groups O, OM and ORM. The data suggest that estrogen can exert great influence on the cellular redox balance. The maintenance of physiological estrogen levels may help to avoid the appearance of pulmonary oedema, characteristic of this model of PAH, and right ventricular failure.
Assuntos
Estradiol/farmacologia , Hipertensão Pulmonar/tratamento farmacológico , Estresse Oxidativo , Animais , Western Blotting , Peso Corporal , Diestro/fisiologia , Estradiol/administração & dosagem , Feminino , Glutationa/metabolismo , Ventrículos do Coração/fisiopatologia , Hemodinâmica , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/fisiopatologia , Monocrotalina/administração & dosagem , Monocrotalina/efeitos adversos , Ovariectomia , Óleos de Plantas/administração & dosagem , Artéria Pulmonar/fisiopatologia , Ratos , Ratos Wistar , Óleo de GirassolRESUMO
This study was conducted to analyse the redox status and redox-sensitive proteins that may contribute to a non-genomic mechanism of cardiac hypertrophy induction by hyperthyroidism. Wistar rats, treated with L-thyroxine (T4) during 2 weeks (12 mg·l(-1) in drinking water), presented cardiac hypertrophy (68% higher than control), without signals of liver or lung congestion. Myocardial reduction of the reduced glutathione: oxidized glutathione (GSSG) ratio (45%) (redox status) and elevation in hydrogen peroxide concentration (H(2) O(2) ) (28%) were observed in hyperthyroid as compared with the control. No significant difference was found in thioredoxin (Trx), Trx reductase activity and Nrf2 (a transcriptional factor) protein expression between groups. Redox-sensitive proteins, quantified using Western blot, presented the following results: increased p-ERK: total extracellular-regulated kinase (ERK) (200%) and Bax:Bcl-2 (62%) ratios and reduced total-Akt (63%) and p-Akt (53%) expressions in the hyperthyroid rats as compared with the control. The redox imbalance, associated with increased immunocontent of a protein related to maladaptative growth (ERK) and reduced immunocontent of protein related to cytoprotection/survival (Akt), may suggest that the molecular scenario could favour the decompensation process of cardiac hypertrophy induced by experimental hyperthyroidism.