RESUMEN
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.
Asunto(s)
Sistema Nervioso Autónomo , Hipertensión Pulmonar , Estrés Oxidativo , Remodelación Ventricular , Animales , Sistema Nervioso Autónomo/metabolismo , Sistema Nervioso Autónomo/patología , Sistema Nervioso Autónomo/fisiopatología , Modelos Animales de Enfermedad , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/patología , Hipertensión Pulmonar/fisiopatología , Inflamación/metabolismo , Inflamación/patología , Inflamación/fisiopatología , Masculino , Ratas , Ratas WistarRESUMEN
This study was conducted to test whether oxidative stress activates the intracellular protein kinase B (AKT1) signaling pathway, which culminates with cardiac hypertrophy in experimental hyperthyroidism. Male Wistar rats were divided into four groups: control, vitamin E, thyroxine (T(4)), and T(4)+vitamin E. Hyperthyroidism was induced by T(4) administration (12 mg/l in drinking water for 28 days). Vitamin E treatment was given during the same period via s.c. injections (20 mg/kg per day). Morphometric and hemodynamic parameters were evaluated at the end of the 4-week treatment period. Protein oxidation, redox state (reduced glutathione, GSH/glutathione dissulfide, GSSG), vitamin C, total radical-trapping antioxidant potential (TRAP), hydrogen peroxide (H2O2), and nitric oxide metabolites (NO(X)) were measured in heart homogenates. The p-AKT1/AKT1 ratio, p-glycogen-synthase kinase (GSK)3B/GSK3B ratio, FOS, and JUN myocardial protein expression were also quantified by western blot after 4 weeks. Increases in biochemical parameters, such as protein oxidation (41%), H2O2 (62%), and NO(X) (218%), and increase in the left ventricular end-diastolic pressure were observed in the T(4) group. T(4) treatment also caused a decrease in GSH/GSSG ratio (83%), vitamin C (34%), and TRAP (55%). These alterations were attenuated by vitamin E administration to the hyperthyroid rats. Expression of p-AKT1/AKT1, p-GSK3B/GSK3B, FOS, and JUN were elevated in the T(4) group (by 69, 37, 130, and 33% respectively), whereas vitamin E administration promoted a significant reduction in their expression. These results indicate that oxidative stress plays an important role in cardiac hypertrophy, and suggest redox activation of AKT1 and JUN/FOS signaling pathways with H2O2 acting as a possible intracellular mediator in this adaptive response to experimental hyperthyroidism.
Asunto(s)
Cardiomegalia/etiología , Modelos Animales de Enfermedad , Hipertiroidismo/complicaciones , Transducción de Señal , Animales , Ácido Ascórbico/metabolismo , Western Blotting , Cardiomegalia/metabolismo , Glutatión/metabolismo , Peróxido de Hidrógeno/metabolismo , Masculino , Oxidación-Reducción , Ratas , Ratas Wistar , Tiroxina/sangreRESUMEN
The purpose of the present study was to examine myocardial antioxidant and oxidative stress changes in male and female rats in the presence of physiological sex hormone concentrations and after castration. Twenty-four 9-week-old Wistar rats were divided into four groups of 6 animals each: 1) sham-operated females, 2) castrated females, 3) sham-operated males, and 4) castrated males. When testosterone and estrogen levels were measured by radioimmunoassay, significant differences were observed between the castrated and control groups (both males and females), demonstrating the success of castration. Progesterone and catalase levels did not change in any group. Control male rats had higher levels of glutathione peroxidase (50%) and lower levels of superoxide dismutase (SOD, 14%) than females. Control females presented increased levels of SOD as compared to the other groups. After castration, SOD activity decreased by 29% in the female group and by 14% in the male group as compared to their respective controls. Lipid peroxidation (LPO) was assessed to evaluate oxidative damage to cardiac membranes by two different methods, i.e., TBARS and chemiluminescence. LPO was higher in male controls compared to female controls when evaluated by both methods, TBARS (360%) and chemiluminescence (46%). Castration induced a 200% increase in myocardial damage in females as determined by TBARS and a 20% increase as determined by chemiluminescence. In males, castration did not change LPO levels. These data suggest that estrogen may have an antioxidant role in heart muscle, while testosterone does not.
Asunto(s)
Antioxidantes/metabolismo , Hormonas Esteroides Gonadales/metabolismo , Miocardio/enzimología , Estrés Oxidativo , Análisis de Varianza , Animales , Castración , Femenino , Depuradores de Radicales Libres/análisis , Depuradores de Radicales Libres/metabolismo , Glutatión Peroxidasa/análisis , Glutatión Peroxidasa/metabolismo , Peroxidación de Lípido/fisiología , Mediciones Luminiscentes , Masculino , Miocardio/patología , Ratas , Ratas Wistar , Superóxido Dismutasa/análisis , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido TiobarbitúricoRESUMEN
The purpose of the present study was to examine myocardial antioxidant and oxidative stress changes in male and female rats in the presence of physiological sex hormone concentrations and after castration. Twenty-four 9-week-old Wistar rats were divided into four groups of 6 animals each: 1) sham-operated females, 2) castrated females, 3) sham-operated males, and 4) castrated males. When testosterone and estrogen levels were measured by radioimmunoassay, significant differences were observed between the castrated and control groups (both males and females), demonstrating the success of castration. Progesterone and catalase levels did not change in any group. Control male rats had higher levels of glutathione peroxidase (50 percent) and lower levels of superoxide dismutase (SOD, 14 percent) than females. Control females presented increased levels of SOD as compared to the other groups. After castration, SOD activity decreased by 29 percent in the female group and by 14 percent in the male group as compared to their respective controls. Lipid peroxidation (LPO) was assessed to evaluate oxidative damage to cardiac membranes by two different methods, i.e., TBARS and chemiluminescence. LPO was higher in male controls compared to female controls when evaluated by both methods, TBARS (360 percent) and chemiluminescence (46 percent). Castration induced a 200 percent increase in myocardial damage in females as determined by TBARS and a 20 percent increase as determined by chemiluminescence. In males, castration did not change LPO levels. These data suggest that estrogen may have an antioxidant role in heart muscle, while testosterone does not
Asunto(s)
Animales , Masculino , Femenino , Ratas , Antioxidantes , Hormonas Esteroides Gonadales , Miocardio , Estrés Oxidativo , Análisis de Varianza , Castración , Depuradores de Radicales Libres , Glutatión Peroxidasa , Peroxidación de Lípido , Mediciones Luminiscentes , Miocardio , Ratas Wistar , Superóxido Dismutasa , Sustancias Reactivas al Ácido TiobarbitúricoRESUMEN
Rats were made hypertensive by the administration of the nitric oxide synthase inhibitor nitro-L-arginine (LNA, 2.74 mmol/L) in drinking water for 7 d. Hearts from hemodynamically assessed animals were analyzed for lipid peroxidation (LPO), gamma-glutamylcysteine-synthetase (gamma-GCS), glutathione disulfide reductase (GR), glutathione peroxidase (GSHPx), catalase (CAT), superoxide dismutase (SOD), and total radical trapping potential (TRAP) activities. LNA treatment increased the mean arterial blood pressure by 46% and the heart rate by 22% without changing plasma renin activity. LNA treatment resulted in a 30% increase in LPO. gamma-GCS was reduced by 48% and GR by 36% in the cardiac tissue of hypertensive rats as compared to controls. The activity of nonselenium GSHPx was reduced by 27%, and selenium-dependent GSHPx activity in the heart was not affected by LNA treatment. In hypertensive rats, SOD activity was increased by 16%, and CAT was decreased by 46%. TRAP was lower (27%) in the myocardium of hypertensive rats than in that of controls. These data suggest that LNA-induced hypertension is associated with increased myocardial oxidative stress.
Asunto(s)
Antioxidantes/metabolismo , Inhibidores Enzimáticos/farmacología , Hipertensión/inducido químicamente , Hipertensión/metabolismo , Miocardio/metabolismo , Óxido Nítrico Sintasa/antagonistas & inhibidores , Nitroarginina/farmacología , Estrés Oxidativo/fisiología , Animales , Catalasa/metabolismo , Glutamato-Cisteína Ligasa/metabolismo , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Corazón/efectos de los fármacos , Hipertensión/enzimología , Masculino , Miocardio/enzimología , Ratas , Ratas Wistar , Renina/sangre , Superóxido Dismutasa/metabolismoRESUMEN
Reactive oxygen species are formed in physiological and pathological conditions in mammalian tissues. Because of their high reactivity, they may interact with biomolecules, inducing oxidative injury. Increases in lipid peroxidation can result in oxidative damage to cellular membranes. Protection against oxidative damage is provided by enzymatic and non-enzymatic antioxidant defenses. Antioxidant enzyme activities and lipid peroxidation, as an index of oxidative stress injury, were evaluated in different seasons over one year in the heart and liver of rats, maintained on a 12 h light and dark cycle. Glutathione peroxidase and catalase activities, in both tissues, were maximal in the summer season. Lipid peroxidation in the heart was maximal in the spring as compared to the other seasons and it did not vary in the liver during the year. These findings suggest that any study of antioxidants or oxidative stress must take into account such seasonal variations for a more precise analysis of changes due to any pathological condition.
Asunto(s)
Catalasa/metabolismo , Glutatión Peroxidasa/metabolismo , Hígado/metabolismo , Miocardio/metabolismo , Estrés Oxidativo , Estaciones del Año , Animales , Peroxidación de Lípido , Masculino , Ratas , Ratas WistarRESUMEN
A cross-sectional study of morphological age changes with special reference to senescence has been conducted on the females of the Jat-Sikh and Bania communities of Punjab (India). These two communities are endogamous at caste level. The Jat-Sikh is traditionally an agriculturist community, mostly residing in the villages, whereas the Bania is traditionally a trading community and is living in cities. The data were collected during 1975-76 on 502 Jat-Sikh and 510 Bania females, ranging in age from 20 to 80 years. Weight, stature, sitting height and subischial length have been reported in the present paper. A peak in weight of 54.53 kg at age-group 40-44 in Jat-Sikhs and 58.01 kg at age-group 45-49 in Banias have been observed after which a decline sets in. The stature as been found to decrease continuously with advancing age from age group 20-24 in Bania and 30-34 in Jat-Sikhs up to age group 70+ giving a total decrement of 5.78 cm in Jat-Sikhs and 8.66 cm in Banias. Sitting height seems to play a major role in the shrinkage of stature contributing about 4.50 cm in Jat-Sikhs and 6.71 cm in Banias, whereas subischial length has been found to decrease only by 1.65 cm in Jat-Sikhs and 1.95 cm in Bania females. The females of the present series have been compared with American, British and rural Colombian females.