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1.
Mol Cell Endocrinol ; 591: 112279, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38797355

RESUMEN

Isoproterenol administration is associated with cardiac inflammation and decreased NO availability. Melatonin has been reported to have cardioprotective effect. The aim of this study was to investigate the effect of melatonin on NO bioavailability and inflammation in myocardial injury induced by isoproterenol. Isoproterenol was administrated in male Wistar rats for 7 days to induce cardiac injury. The animals were divided into 3 groups: Control, Isoproterenol, Isoproterenol + Melatonin. Animals received melatonin for 7 days. Echocardiographic analysis was performed and the hearts were collected for molecular analysis. Animals that received isoproterenol demonstrated a reduction in left ventricle systolic and diastolic diameter, indicating the presence of concentric hypertrophy. Melatonin was able to attenuate this alteration. Melatonin also improved NO bioavailability and decreased NF-κß, TNFα and IL-1ß expression. In conclusion, melatonin exhibited a cardioprotective effect which was associated with improving NO bioavailability and decreasing the pro-inflammatory proteins.


Asunto(s)
Disponibilidad Biológica , Isoproterenol , Melatonina , Óxido Nítrico , Ratas Wistar , Animales , Melatonina/farmacología , Óxido Nítrico/metabolismo , Masculino , Ratas , Cardiotónicos/farmacología , Miocardio/metabolismo , Miocardio/patología , FN-kappa B/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-1beta/metabolismo , Lesiones Cardíacas/metabolismo , Lesiones Cardíacas/inducido químicamente , Lesiones Cardíacas/patología
2.
Biochim Biophys Acta Mol Cell Res ; 1871(4): 119704, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38462075

RESUMEN

Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance (PVR), right ventricular (RV) failure and premature death. Compounds with vasodilatory characteristics, such as ß-caryophyllene, could be promising therapeutics for PAH. This study aimed to determine the effects of free and nanoemulsified ß-caryophyllene in lung oxidative stress and heart function in PAH rats. Male Wistar rats (170 g, n = 6/group) were divided into four groups: control (CO), monocrotaline (MCT), monocrotaline + ß-caryophyllene (MCT-Bcar) and monocrotaline + nanoemulsion with ß-caryophyllene (MCT-Nano). PAH was induced by MCT (60 mg/kg i.p.), and 7 days later, treatment with ß-caryophyllene, either free or in a nanoemulsion (by gavage, 176 mg/kg/day) or vehicle was given for 14 days. Echocardiographic and hemodynamic measurements were performed, and after, the RV was collected for morphometry and the lungs for evaluation of oxidative stress, antioxidant enzymes, total sulfhydryl compounds, nitric oxide synthase (NOS) activity and endothelin-1 receptor expression. RV hypertrophy, increased PVR and RV systolic and diastolic pressures (RVSP and RVEDP, respectively) and increased mean pulmonary arterial pressure (mPAP) were observed in the MCT group. Treatment with both free and nanoemulsified ß-caryophyllene reduced RV hypertrophy, mPAP, RVSP and lipid peroxidation. The reduction in RVSP was more pronounced in the MCT-Nano group. Moreover, RVEDP decreased only in the MCT-Nano group. These treatments also increased superoxide dismutase, catalase and NOS activities and decreased endothelin-1 receptors expression. Both ß-caryophyllene formulations improved mPAP, PVR and oxidative stress parameters. However, ß-caryophyllene in a nanoemulsion was more effective in attenuating the effects of PAH.


Asunto(s)
Hipertensión Pulmonar , Sesquiterpenos Policíclicos , Hipertensión Arterial Pulmonar , Ratas , Masculino , Animales , Hipertensión Arterial Pulmonar/metabolismo , Monocrotalina/toxicidad , Monocrotalina/metabolismo , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/metabolismo , Ratas Wistar , Arteria Pulmonar/metabolismo , Hipertrofia Ventricular Derecha/inducido químicamente , Hipertrofia Ventricular Derecha/metabolismo
3.
Can J Physiol Pharmacol ; 101(2): 106-116, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36661235

RESUMEN

Inflammatory pathways of Toll-like receptor 4 (TLR4) and NLRP3 inflammasome contribute to acute myocardial infarction (AMI) pathophysiology. The hypoxia-inducible factor 1α (HIF-1α), however, is a key transcription factor related to cardioprotection. This study aimed to compare the influence of carvedilol and thyroid hormones (TH) on inflammatory and HIF-1α proteins and on cardiac haemodynamics in the infarcted heart. Male Wistar rats were allocated into five groups: sham-operated group (SHAM), infarcted group (MI), infarcted treated with the carvedilol group (MI + C), infarcted treated with the TH group (MI + TH), and infarcted co-treated with the carvedilol and TH group (MI + C + TH). Haemodynamic analysis was assessed 15 days post-AMI. The left ventricle (LV) was collected for morphometric and Western blot analysis. The MI group presented LV systolic pressure reduction, LV end-diastolic pressure elevation, and contractility index decrease compared to the SHAM group. The MI + C, MI + TH, and MI + C + TH groups did not reveal such alterations compared to the SHAM group. The MI + TH and MI + C + TH groups presented reduced MyD88 and NLRP3 and increased HIF-1α levels. In conclusion, all treatments preserve the cardiac haemodynamic, and only TH, as isolated treatment or in co-treatment with carvedilol, was able to reduce MyD88 and NLRP3 and increase HIF-1α in the infarcted heart.


Asunto(s)
Factor 88 de Diferenciación Mieloide , Infarto del Miocardio , Animales , Masculino , Ratas , Carvedilol/farmacología , Carvedilol/uso terapéutico , Factor 88 de Diferenciación Mieloide/metabolismo , Infarto del Miocardio/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ratas Wistar , Hormonas Tiroideas
4.
Arch Physiol Biochem ; 128(6): 1516-1523, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32551929

RESUMEN

CONTEXT: Infarction leads to a decrease in NO bioavailability in the erythrocytes. Thyroid hormones (TH) present positive effects after infarction. However, there are no studies evaluating the effects of cardioprotective doses of TH in the erythrocytes after infarction. OBJECTIVE: This study aimed to evaluate the effects of TH in NO bioavailability and oxidative stress parameters in the erythrocytes of infarcted rats. MATERIAL AND METHODS: Wistar rats were allocated into the three groups: Sham-operated (SHAM), infarcted (AMI) and infarcted + TH (AMIT). AMIT rats received T4 and T3 for 12 days by gavage. Subsequently, the animals were evaluated by echocardiography and the LV and erythrocytes were collected. RESULTS: TH improved NO bioavailability and increased catalase activity in the erythrocytes. Besides that, TH increased HIF-1α in the heart. CONCLUSION: TH seems to be positive for erythrocytes preventing a decrease in NO bioavailability and increasing antioxidant enzymatic defense after infarction.


Asunto(s)
Antioxidantes , Infarto del Miocardio , Animales , Ratas , Catalasa , Eritrocitos , Infarto del Miocardio/prevención & control , Infarto del Miocardio/metabolismo , Ratas Wistar , Hormonas Tiroideas/farmacología , Óxido Nítrico
5.
J Cardiovasc Pharmacol ; 76(6): 698-707, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33105324

RESUMEN

Cellular death and survival signaling plays a key role in the progress of adverse cardiac remodeling after acute myocardial infarction (AMI). Therapeutic strategies, such as co-treatment with beta-blocker carvedilol and thyroid hormones (THs), give rise to new approaches that can sustain the cellular homeostasis after AMI. Therefore, we sought to investigate the effects of carvedilol and TH co-administration on apoptosis and survival proteins and on cardiac remodeling after AMI. Male Wistar rats were distributed in 5 groups as follows: sham-operated group (SHAM), infarcted group (MI), infarcted plus carvedilol group (MI+C), infarcted plus TH group (MI+TH), and infarcted plus carvedilol and TH co-treatment group (MI+C+TH). Echocardiographic analysis was performed, and hearts were collected for western blot evaluation. The MI group presented systolic posterior wall thickness loss, an increase in the wall tension index, and an increase in atrial natriuretic peptide tissue levels than the SHAM group. However, in the MI+C+TH group, these parameters were equally to the SHAM group. Moreover, whereas the MI group showed Bax protein expression elevated in relation to the SHAM group, the MI+C+TH group presented Bax reduction and also Akt activation compared with the MI group. In addition, the MI+TH group revealed beta-1 adrenergic receptor (ß1AR) upregulation compared with the MI and MI+C groups, whereas the MI+C+TH group presented lower levels of ß1AR in relation to the SHAM and MI+TH groups. In conclusion, we suggest that carvedilol and TH co-administration may mediate its cardioprotective effects against adverse cardiac remodeling post-AMI through the Bax reduction, Akt activation, and ß1AR decrease.


Asunto(s)
Antagonistas de Receptores Adrenérgicos alfa 1/farmacología , Proteínas Reguladoras de la Apoptosis/metabolismo , Apoptosis/efectos de los fármacos , Carvedilol/farmacología , Infarto del Miocardio/tratamiento farmacológico , Miocardio/metabolismo , Tiroxina/farmacología , Triyodotironina/farmacología , Animales , Modelos Animales de Enfermedad , Masculino , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Miocardio/patología , Fosforilación , Proteínas Proto-Oncogénicas c-akt , Ratas Wistar , Receptores Adrenérgicos alfa 1/efectos de los fármacos , Receptores Adrenérgicos alfa 1/metabolismo , Transducción de Señal
6.
Exp Physiol ; 105(9): 1561-1570, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32667095

RESUMEN

NEW FINDINGS: What is the central question of this study? Does thyroid hormone treatment given after myocardial infarction preserve left ventricular function and treadmill exercise performance, and improve parameters of oxidative stress in the right ventricle and lungs of Wistar rats? What is the main finding and its importance? Thyroid hormone treatment improved the performance of the maximum exercise test in infarcted rats and induced effects in the heart and lungs that were similar to those observed with exercise training. This suggests there is a significant value of thyroid hormones for preserving exercise tolerance after myocardial infarction. ABSTRACT: Left ventricular myocardial infarction (MI) provokes damage in the heart and in other tissues, such as right ventricle and lungs. The present study elucidated whether thyroid hormone treatment (THT) may present positive effects in heart and lungs after MI, and whether or not these effects are similar to those of exercise training (ET). Male Wistar rats were divided into four groups: sham operated (SHAM), infarcted (MI), infarcted + exercise training (MIE), and infarcted + thyroid hormones (MIH). A maximum exercise test, left ventricle echocardiography, pulmonary histology, and oxidative stress in the right ventricle and lung were evaluated. THT and ET both reduced left ventricular dilatation and end-diastolic wall stress indexes to a similar extent. MI accentuated the content of macrophages and inflammatory infiltrate in the lungs, which was partially prevented in the MIH and MIE groups. THT and ET presented similar effects in the heart and lungs, and both improved the performance of the maximum exercise test in infarcted animals.


Asunto(s)
Prueba de Esfuerzo , Infarto del Miocardio/terapia , Condicionamiento Físico Animal , Hormonas Tiroideas/farmacología , Función Ventricular Izquierda , Animales , Ecocardiografía , Corazón , Pulmón , Masculino , Miocardio , Estrés Oxidativo , Ratas Wistar
7.
Appl Physiol Nutr Metab ; 45(9): 987-995, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32191845

RESUMEN

This study explored the effect of pterostilbene (PTS) complexed with hydroxypropyl-ß-cyclodextrin (HPßCD) on right heart function, glutathione and glutaredoxin systems, and the expression of redox-sensitive proteins involved with regulation calcium levels in the experimental model of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). After 7 days of PAH induction, rats received daily doses of the PTS:HPßCD complex (corresponding to 25, 50, or 100 mg·kg-1 of PTS) or vehicle (control group, CTR0) (an aqueous solution containing HPßCD; CTR0 and MCT0 (MCT group that did not receive PTS treatment)) via oral administration for 2 weeks. The results showed that the PTS:HPßCD complex increased the content of reduced glutathione and the activity of glutathione-S-transferase and glutaredoxin in the right ventricle (RV) of MCT-treated rats in a dose-dependent manner. Additionally, at higher doses, it also prevented the reduction of stroke volume and cardiac output, prevented myocardial performance index (MPI) increase, reduced lipoperoxidation, reduced total phospholamban, and increased the expression of sarcoplasmic reticulum calcium ATPase in the RV of MCT-treated rats. These results demonstrate that the PTS:HPßCD complex has a dose-dependent antioxidant mechanism that results in improved cardiac function in experimental right heart failure. Our results open a field of possibilities to PTS administration as new therapeutic approach to conventional therapy for right ventricular dysfunction. Novelty Pterostilbene complexed with hydroxypropyl-ß-cyclodextrin could be a new therapeutic approach. Pterostilbene complexed with hydroxypropyl-ß-cyclodextrin reestablishes redox homeostasis through glutathione metabolism modulation, leading to an improved MPI in pulmonary arterial hypertension-provoked right heart failure.


Asunto(s)
Insuficiencia Cardíaca/tratamiento farmacológico , Estrés Oxidativo , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo , Estilbenos/uso terapéutico , 2-Hidroxipropil-beta-Ciclodextrina/uso terapéutico , Animales , Antioxidantes/farmacología , Calcio/metabolismo , Ecocardiografía , Glutatión/metabolismo , Ventrículos Cardíacos/efectos de los fármacos , Hipertensión Pulmonar/inducido químicamente , Peroxidación de Lípido , Masculino , Monocrotalina , Ratas , Ratas Wistar , Volumen Sistólico
8.
J Biosci ; 43(5): 887-895, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30541949

RESUMEN

Hyperthyroidism can lead to the activation of proteins which are associated with inflammation, apoptosis, hypertrophy, and heart failure. This study aimed to explore the inflammatory and apoptotic proteins involved in the hyperthyroidism-induced cardiac hypertrophy establishment. Male Wistar rats were divided into control and hyperthyroid (12 mg/L L-thyroxine, in drinking water for 28 days) groups. The expression of inflammatory and apoptotic signaling proteins was quantified in the left ventricle by Western blot. Hyperthyroidism was confirmed by evaluation of T3 and T4 levels, as well as cardiac hypertrophy development. There was no change in the expression of HSP70, HIF1-α, TNF-α, MyD88, p-NFκB, NFκB, p-p38, and p38. Reduced expression of p53 and PGC1-α was associated with increased TLR4 and decreased IL-10 expression. Decreased Bcl-2 expression and increased Bax/Bcl-2 ratio were also observed. The results suggest that reduced PGC1-α and IL-10, and elevated TLR4 proteins expression could be involved with the diminished mitochondrial biogenesis and anti-inflammatory response, as well as cell death signaling, in the establishment of hyperthyroidism-induced maladaptive cardiac hypertrophy.


Asunto(s)
Cardiomegalia/genética , Hipertiroidismo/genética , Interleucina-10/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Receptor Toll-Like 4/genética , Animales , Apoptosis/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Cardiomegalia/inducido químicamente , Cardiomegalia/metabolismo , Cardiomegalia/patología , Regulación de la Expresión Génica , Corazón/efectos de los fármacos , Corazón/fisiopatología , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/patología , Hipertiroidismo/inducido químicamente , Hipertiroidismo/metabolismo , Hipertiroidismo/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Interleucina-10/metabolismo , Masculino , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/patología , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Wistar , Transducción de Señal , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/patología , Tiroxina/administración & dosificación , Tiroxina/sangre , Receptor Toll-Like 4/metabolismo , Triyodotironina/sangre , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismo
9.
Free Radic Res ; 52(9): 988-999, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30203709

RESUMEN

Oxidative stress alters signalling pathways for survival and cell death favouring the adverse remodelling of postmyocardial remnant cardiomyocytes, promoting functional impairment. The administration of pterostilbene (PTS), a phytophenol with antioxidant potential, can promote cardioprotection and represents a therapeutic alternative in acute myocardial infarction (AMI). The present study aims to explore the effects of oral administration of PTS complexed with hydroxypropyl-ß-cyclodextrin HPßCD (PTS:HPßCD complex) on the glutathione cycle, thiol protein activities and signalling pathways involving the protein kinase B (AKT) and glycogen synthase kinase-3ß (GSK-3ß) proteins in the left ventricle (LV) of infarcted rats. Animals were submitted to acute myocardial infarction through surgical ligation of the descending anterior branch of the left coronary artery and received over 8 days, by gavage, PTS:HPßCD complex at dose of 100 mg kg-1 day-1 (AMI + PTS group) or vehicle (aqueous solution with HPßCD) divided into Sham-operated (SHAM) and infarcted (AMI) groups. The results showed that the PBS: HPßCD complex decreased lipid peroxidation, prevented the decrease in thioredoxin reductase (TRxR) activity, and increased the activity of glutathione-S-transferase (GST) and glutaredoxin (GRx). Additionally, the expression of nuclear factor-erythroid two (Nrf2) and p-GSK-3ß was increased, whereas the p-GSK-3ß/GSK-3ß ratio was reduced in the LV of the infarcted animals. Overall, the PTS:HPßCD complex modulates activity of thiol-dependent enzymes and induces to the expression of antioxidant proteins, improving systolic function and mitigating the adverse cardiac remodelling post infarction.


Asunto(s)
Glucógeno Sintasa Quinasa 3 beta/genética , Infarto del Miocardio/tratamiento farmacológico , Factor 2 Relacionado con NF-E2/genética , Estilbenos/administración & dosificación , Función Ventricular Izquierda/efectos de los fármacos , Animales , Antioxidantes/administración & dosificación , Antioxidantes/química , Apoptosis/efectos de los fármacos , Cardiotónicos/administración & dosificación , Cardiotónicos/química , Ciclodextrinas/administración & dosificación , Ciclodextrinas/química , Modelos Animales de Enfermedad , Humanos , Peroxidación de Lípido/efectos de los fármacos , Infarto del Miocardio/genética , Infarto del Miocardio/fisiopatología , Miocitos Cardíacos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Fosforilación/efectos de los fármacos , Ratas , Estilbenos/química , Función Ventricular Izquierda/genética , Función Ventricular Izquierda/fisiología
10.
Life Sci ; 196: 93-101, 2018 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-29366748

RESUMEN

AIMS: This study aimed to investigate whether beneficial effects of thyroid hormones are comparable to those provided by the aerobic exercise training, to verify its applicability as a therapeutic alternative to reverse the pathological cardiac remodeling post-infarction. MATERIALS AND METHODS: Male rats were divided into SHAM-operated (SHAM), myocardial infarction (MI), MI subjected to exercise training (MIE), and MI who received T3 and T4 treatment (MIH) (n = 8/group). MI, MIE and MIH groups underwent an infarction surgery while SHAM was SHAM-operated. One-week post-surgery, MIE and MIH groups started the exercise training protocol (moderate intensity on treadmill), or the T3 (1.2 µg/100 g/day) and T4 (4.8 µg/100 g/day) hormones treatment by gavage, respectively, meanwhile SHAM and MI had no intervention for 9 weeks. The groups were accompanied until 74 days after surgery, when all animals were anesthetized, left ventricle echocardiography and femoral catheterization were performed, followed by euthanasia and left ventricle collection for morphological, oxidative stress, and intracellular kinases expression analysis. KEY FINDINGS: Thyroid hormones treatment was more effective in cardiac dilation and infarction area reduction, while exercise training provided more protection against fibrosis. Thyroid hormones treatment increased the lipoperoxidation and decreased GSHPx activity as compared to MI group, increased the t-Akt2 expression as compared to SHAM group, and increased the vascular parasympathetic drive. SIGNIFICANCE: Thyroid hormones treatment provided differential benefits on the LV function and autonomic modulation as compared to the exercise training. Nevertheless, the redox unbalance induced by thyroid hormones highlights the importance of more studies targeting the ideal duration of this treatment.


Asunto(s)
Terapia por Ejercicio , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/terapia , Sistema Nervioso Parasimpático/efectos de los fármacos , Condicionamiento Físico Animal , Tiroxina/uso terapéutico , Triyodotironina/uso terapéutico , Animales , Ecocardiografía , Fibrosis , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/patología , Masculino , Infarto del Miocardio/diagnóstico por imagen , Estrés Oxidativo/efectos de los fármacos , Sistema Nervioso Parasimpático/fisiopatología , Proteínas Proto-Oncogénicas c-akt/biosíntesis , Proteínas Proto-Oncogénicas c-akt/genética , Ratas , Ratas Wistar , Sistema Nervioso Simpático/efectos de los fármacos , Sistema Nervioso Simpático/fisiopatología
11.
Can J Physiol Pharmacol ; 96(3): 295-303, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28854338

RESUMEN

The aim of this study was to evaluate the impact of ovariectomy on oxidative stress in the right ventricle (RV) of female rats with pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). Rats were divided into 4 groups (n = 6 per group): sham (S), sham + MCT (SM), ovariectomized (O), and ovariectomized + MCT (OM). MCT (60 mg·kg-1 i.p.) was injected 1 week after ovariectomy or sham surgery. Three weeks later, echocardiographic analysis and RV catheterisation were performed. RV morphometric, biochemical, and protein expression analysis through Western blotting were done. MCT promoted a slight increase in pulmonary artery pressure, without differences between the SM and OM groups, but did not induce RV hypertrophy. RV hydrogen peroxide increased in the MCT groups, but SOD, CAT, and GPx activities were also enhanced. Non-classical antioxidant defenses diminished in ovariectomized groups, probably due to a decrease in the nuclear factor Nrf2. Hemoxygenase-1 and thioredoxin-1 protein expression was increased in the OM group compared with SM, being accompanied by an elevation in the estrogen receptor ß (ER-ß). Hemoxygenase-1 and thioredoxin-1 may be involved in the modulation of oxidative stress in the OM group, and this could be responsible for attenuation of PAH and RV remodeling.


Asunto(s)
Antioxidantes/metabolismo , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/metabolismo , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/metabolismo , Monocrotalina/efectos adversos , Ovariectomía/efectos adversos , Adaptación Fisiológica/efectos de los fármacos , Animales , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Ventrículos Cardíacos/fisiopatología , Hemodinámica/efectos de los fármacos , Hipertensión Pulmonar/fisiopatología , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Remodelación Ventricular/efectos de los fármacos
12.
Mol Cell Endocrinol ; 461: 112-121, 2018 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-28870779

RESUMEN

Epitestosterone is the 17α-epimer of testosterone and has been described as an anti-androgen, since it inhibits the effects produced by testosterone and dihydrotestosterone via the nuclear androgen receptor (nAR). However, epitestosterone also displays an effect which is similar to the non-classical effect of testosterone, depolarizing the membrane potential of Sertoli cells and inducing a rapid Ca2+ uptake. This study aimed to investigate the effects of a treatment with epitestosterone on developmental parameters of immature rats. Animals were chemically castrated by using the gonadotropin-releasing hormone (GnRH) antagonist cetrorelix and then received a replacement of 7 days with epitestosterone or testosterone. Replacement with either epitestosterone or testosterone restored the anogenital distance (AGD) and testicular weight which had been reduced by chemical castration. The immunocontent of nAR and the nAR-immunoreactivity were reduced by epitestosterone treatment in the testis of both castrated and non-castrated animals. Furthermore, testosterone was unable of changing the membrane potential of Sertoli cells through its non-classical action in the group of animals castrated and replaced with epitestosterone. In conclusion, in relation to the level of protein expression of nAR epitestosterone acts as an anti-androgen. However, it acts in the same way as testosterone when genital development parameters are evaluated. Moreover, in castrated rats epitestosterone suppressed the non-classical response of testosterone, changing the pattern of testosterone signalling via a membrane mechanism in Sertoli cells.


Asunto(s)
Castración , Epitestosterona/farmacología , Terapia de Reemplazo de Hormonas , Testículo/crecimiento & desarrollo , Testosterona/farmacología , Animales , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Hormona Liberadora de Gonadotropina/análogos & derivados , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Hormona Liberadora de Gonadotropina/metabolismo , Hormona Liberadora de Gonadotropina/farmacología , Masculino , Potenciales de la Membrana/efectos de los fármacos , Ratas Wistar , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Túbulos Seminíferos/efectos de los fármacos , Túbulos Seminíferos/metabolismo , Células de Sertoli/efectos de los fármacos , Células de Sertoli/metabolismo , Testículo/efectos de los fármacos
13.
Metab Brain Dis ; 33(1): 333-342, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29260360

RESUMEN

Several studies have examined neonatal diabetes, a rare disease characterized by hyperglycemia and low insulin levels that is usually diagnosed in the first 6 month of life. Recently, the effects of diabetes on the brain have received considerable attention. In addition, hyperglycemia may perturb brain function and might be associated with neuronal death in adult rats. However, few studies have investigated the damaging effects of neonatal hyperglycemia on the rat brain during central nervous system (CNS) development, particularly the mechanisms involved in the disease. Thus, in the present work, we investigated whether neonatal hyperglycemia induced by streptozotocin (STZ) promoted cell death and altered the levels of proteins involved in survival/death pathways in the rat brain. Cell death was assessed using FluoroJade C (FJC) staining and the expression of the p38 mitogen-activated protein kinase (p38), phosphorylated-c-Jun amino-terminal kinase (p-JNK), c-Jun amino-terminal kinase (JNK), protein kinase B (Akt), phosphorylated-protein kinase B (p-Akt), glycogen synthase kinase-3ß (Gsk3ß), B-cell lymphoma 2 (Bcl2) and Bcl2-associated X protein (Bax) protein were measured by Western blotting. The main results of this study showed that the metabolic alterations observed in diabetic rats (hyperglycemia and hypoinsulinemia) increased p38 expression and decreased p-Akt expression, suggesting that cell survival was altered and cell death was induced, which was confirmed by FJC staining. Therefore, the metabolic conditions observed during neonatal hyperglycemia may contribute to the harmful effect of diabetes on the CNS in a crucial phase of postnatal neuronal development.


Asunto(s)
Encéfalo/patología , Muerte Celular/fisiología , Hiperglucemia/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Animales , Encéfalo/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Femenino , Sistema de Señalización de MAP Quinasas/fisiología , Masculino , Neuronas/metabolismo , Fosforilación , Ratas Wistar , Proteína X Asociada a bcl-2/metabolismo
14.
Mol Cell Endocrinol ; 461: 132-142, 2018 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-28888669

RESUMEN

Myocardial infarction leads to oxidative stress and promotes activation of the TLR4/NF-κß proinflammatory pathway. Thyroid hormones (TH) are known to be cardioprotective after infarction. However, there are no studies evaluating whether TH could modulate this pathway in the heart. This study aimed to verify the effect of thyroid hormones on the TLR4/NF-κß pathway after myocardial infarction. Male Wistar rats were allocated into the following groups: Sham-operated (SHAM), sham-operated + TH (SHAMT), infarcted (AMI) and infarcted + TH (AMIT). The treated rats received T4 and T3 (8 and 2 µg 100 g-1 day-1) for 12 days by gavage. Subsequently, the animals were evaluated by echocardiography and euthanized, and the left ventricle was collected for biochemical and molecular analyses. TH modulates TLR4/NF-κß expression in the infarcted hearts of rats and decreases xanthine oxidase expression. These effects were related to cardiac functional improvement after infarction. The cardioprotective effects of T3 and T4 seem to involve an anti-inflammatory action.


Asunto(s)
Ventrículos Cardíacos/fisiopatología , Inflamación/patología , Infarto del Miocardio/fisiopatología , FN-kappa B/metabolismo , Transducción de Señal , Hormonas Tiroideas/farmacología , Receptor Toll-Like 4/metabolismo , Animales , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/patología , Inflamación/metabolismo , Masculino , Factor 88 de Diferenciación Mieloide/metabolismo , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/patología , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , Receptores de Hormona Tiroidea/metabolismo , Transducción de Señal/efectos de los fármacos , Xantina Oxidasa/metabolismo
15.
Biomed Pharmacother ; 95: 965-973, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28915538

RESUMEN

Here we aimed to compare the beneficial effects of T3 and T4 hormone treatment to those provided by aerobic exercise training in Wistar rats post-myocardial infarction (MI). Rats in one group were SHAM-operated and in the other group were subjected to MI surgery. One week after surgery, the MI group animals either received T3 and T4 hormones by gavage or underwent a low intensity aerobic exercise training protocol on a treadmill, and both treatments lasted until 10 weeks after MI. Untreated SHAM-operated and MI groups were also followed for the same duration. The cardiac function was assessed by echocardiography and catheterization, followed by blood collection (to measure T3, T4, and TSH hormones), and euthanasia. The lung, liver, heart, and tibia were collected (to assess hypertrophy and congestion indices). The left ventricle homogenate (without a scar) was used for the analyses of calcium handling proteins. Results showed that enhanced cardiac function was promoted by both interventions, with infarct size reduction, increased ejection fraction, and diastolic posterior wall thickness, but no alterations in heart rate, cardiac output, or T3, T4, and TSH levels. There was a positive force-frequency relationship accompanied by increased α-MHC, as well as decreased HSP70 protein expression. In conclusion, the effects of T3 and T4 hormone treatments were similar, and in some parameters superior, to those provided by the aerobic exercise training. Thus, lower doses of thyroid hormones could be more suitable as a coadjuvant treatment after MI, as a plausible alternative for patients who are intolerant to aerobic exercise training.


Asunto(s)
Pruebas de Función Cardíaca , Corazón/fisiopatología , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/fisiopatología , Condicionamiento Físico Animal , Tiroxina/uso terapéutico , Triyodotironina/uso terapéutico , Animales , Transporte Biológico/efectos de los fármacos , Calcio/metabolismo , Cateterismo Cardíaco , Ecocardiografía , Corazón/efectos de los fármacos , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/fisiopatología , Masculino , Contracción Miocárdica/efectos de los fármacos , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/patología , Cadenas Pesadas de Miosina/metabolismo , Ratas Wistar , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Retículo Sarcoplasmático/efectos de los fármacos , Retículo Sarcoplasmático/metabolismo , Tirotropina/metabolismo , Tiroxina/farmacología , Triyodotironina/farmacología
16.
J Cardiovasc Pharmacol ; 69(2): 79-85, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27798416

RESUMEN

Copaiba oil comes from an Amazonian tree and has been used as an alternative medicine in Brazil. However, it has not been investigated yet in the treatment of cardiovascular diseases. This study was designed to test whether copaiba oil or nanocapsules containing this oil could modulate monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Male Wistar rats (170 ± 20 g) received oil or nanocapsules containing this oil (400 mg/kg) by gavage daily for 1 week. At the end of this period, a single injection of MCT (60 mg/kg i.p.) was administered and measurements were performed after 3 weeks. The animals were divided into 6 groups: control, copaiba oil, nanocapsules with copaiba oil, MCT, oil + MCT, and nanocapsules + MCT. Afterward, echocardiographic assessments were performed, and rats were killed to collect hearts for morphometry and oxidative stress. MCT promoted a significant increase in pulmonary vascular resistance, right ventricle (RV) hypertrophy, and RV oxidative stress. Both oil and copaiba nanocapsules significantly reduced RV hypertrophy and oxidative stress. Pulmonary vascular resistance was reduced by copaiba oil in natura but not by nanocapsules. In conclusion, copaiba oil seems to offer protection against MCT-induced PAH. Our preliminary results suggest that copaiba oil may be an important adjuvant treatment for PAH.


Asunto(s)
Fabaceae , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/tratamiento farmacológico , Monocrotalina/toxicidad , Nanocápsulas/administración & dosificación , Aceites de Plantas/administración & dosificación , Animales , Hipertensión Pulmonar/metabolismo , Masculino , Ratas , Ratas Wistar , Resultado del Tratamiento
17.
J Nutr Biochem ; 34: 106-17, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27288935

RESUMEN

This study investigated whether sulforaphane (SFN), a compound found in cruciferous vegetables, could attenuate the progression of post-myocardial infarction (MI) cardiac remodeling. Male Wistar rats (350 g) were allocated to four groups: SHAM (n=8), SHAM+SFN (n=7), MI (n=8) and MI+SFN (n=5). On the third day after surgery, cardiac function was assessed and SFN treatment (5 mg/kg/day) was started. At the end of 25 days of treatment, cardiac function was assessed and heart was collected to measure collagen content, oxidative stress and protein kinase. MI and MI+SFN groups presented cardiac dysfunction, without signs of congestion. Sulforaphane reduced fibrosis (2.1-fold) in infarcted rats, which was associated with a slight attenuation in the cardiac remodeling process. Both infarcted groups presented increases in the oxidative markers xanthine oxidase and 4-hydroxinonenal, as well as a parallel increase in the antioxidant enzymes glutathione peroxidase and superoxide dismutase. Moreover, sulforaphane stimulated the cytoprotective heme oxygenase-1 (HO-1) (38%). Oxidative markers correlated with ERK 1/2 activation. In the MI+SFN group, up-regulation of ERK 1/2 (34%) and Akt (35%), as well as down-regulation of p38 (52%), was observed. This change in the prosurvival kinase balance in the MI+SFN group was related to a down-regulation of apoptosis pathways (Bax/Bcl-2/caspase-3). Sulforaphane was unable to modulate autophagy. Taken together, sulforaphane increased HO-1, which may generate a redox environment in the cardiac tissue favorable to activation of prosurvival and deactivation of prodeath pathways. In conclusion, this natural compound contributes to attenuation of the fibrotic process, which may contribute to mitigation against the progression of cardiac remodeling postinfarction.


Asunto(s)
Antioxidantes/uso terapéutico , Proteínas Reguladoras de la Apoptosis/metabolismo , Ventrículos Cardíacos/efectos de los fármacos , Isotiocianatos/uso terapéutico , Daño por Reperfusión Miocárdica/prevención & control , Estrés Oxidativo/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos , Animales , Antioxidantes/administración & dosificación , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Biomarcadores/sangre , Biomarcadores/metabolismo , Fibrosis , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/fisiopatología , Hemo-Oxigenasa 1/química , Hemo-Oxigenasa 1/metabolismo , Inyecciones Intraperitoneales , Isotiocianatos/administración & dosificación , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/fisiopatología , Distribución Aleatoria , Ratas Wistar , Sulfóxidos
18.
Apoptosis ; 21(2): 184-94, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26659365

RESUMEN

Apoptosis is a key process associated with pathological cardiac remodelling in early-phase post-myocardial infarction. In this context, several studies have demonstrated an anti-apoptotic effect of thyroid hormones (TH). The aim of this study was to evaluate the effects of TH on the expression of proteins associated with the apoptotic process 14 days after infarction. Male Wistar rats (300-350 g) (n = 8/group) were divided into four groups: Sham-operated (SHAM), infarcted (AMI), sham-operated + TH (SHAMT) and infarcted + TH (AMIT). For 12 days, the animals received T3 and T4 [2 and 8 µg/(100 g day)] by gavage. After this, the rats were submitted to haemodynamic and echocardiographic analysis, and then were sacrificed and the heart tissue was collected for molecular analysis. Statistical analyses included two-way ANOVA with Student-Newman-Keuls post test. Ethics Committee number: 23262. TH administration prevented the loss of ventricular wall thickness and improved cardiac function in the infarcted rats 14 days after the injury. AMI rats presented an increase in the pro-apoptotic proteins p53 and JNK. The hormonal treatment prevented this increase in AMIT rats. In addition, TH administration decreased the Bax:Bcl-2 ratio in the infarcted rats. TH administration improved cardiac functional parameters, and decreased the expression of pro-apoptotic proteins 14 days after myocardial infarction.


Asunto(s)
Proteínas Reguladoras de la Apoptosis/metabolismo , Cardiotónicos/administración & dosificación , Infarto del Miocardio/tratamiento farmacológico , Miocardio/metabolismo , Tiroxina/administración & dosificación , Triyodotironina/administración & dosificación , Animales , Proteínas Reguladoras de la Apoptosis/genética , Cardiotónicos/farmacocinética , Evaluación Preclínica de Medicamentos , Expresión Génica , Peroxidación de Lípido , Masculino , Infarto del Miocardio/metabolismo , Miocardio/patología , Oxidación-Reducción , Estrés Oxidativo , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Tiroxina/farmacocinética , Triyodotironina/farmacocinética , Presión Ventricular/efectos de los fármacos
19.
Physiol Behav ; 155: 66-76, 2016 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-26657022

RESUMEN

The present study aimed to analyze the effects of sleep restriction (SR) during pregnancy in rats. The following three groups were studied: home cage (HC pregnant females remained in their home cage), Sham (females were placed in tanks similar to the SR group but with sawdust) and SR (females were submitted to the multiple platform method for 20 h per day from gestational days (GD) 14 to 20). Plasma corticosterone after 6 days of SR was not different among the groups. However, the relative adrenal weight was higher in the SR group compared with the HC group, which suggests possible stress impact. SR during pregnancy reduces the body weight of the female but no changes in liver glycogen, cholesterol and triglycerides, and muscle glycogen were detected. On GD 20, the fetuses of the females submitted to SR exhibited increased brain derived neurotrophic factor (BDNF) in the hippocampus, which indicates that sleep restriction of mothers during the final week of gestation may affect neuronal growth factors in a fetal brain structure, in which active neurogenesis occurs during the deprivation period. However, no changes in the total reactive oxygen species (ROS) in the cortex, hippocampus, or cerebellum of the fetuses were detected. SR females showed no major change in the maternal behavior, and the pups' preference for the mother's odor on postpartum day (PPD) 7 was not altered. On GD 20, the SR females exhibited increased plasma prolactin (PRL) and oxytocin (OT) compared with the HC and Sham groups. The negative outcomes of sleep restriction during delivery could be related, in part, to this hormonal imbalance. Sleep restriction during pregnancy induces different changes compared with the changes described in males and affects both the mother and offspring.


Asunto(s)
Complicaciones del Embarazo/metabolismo , Privación de Sueño/metabolismo , Animales , Encéfalo/embriología , Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Colesterol/metabolismo , Corticosterona/sangre , Femenino , Glucógeno/metabolismo , Hígado/metabolismo , Conducta Materna/fisiología , Músculos/metabolismo , Percepción Olfatoria/fisiología , Oxitocina/sangre , Embarazo , Prolactina/sangre , Distribución Aleatoria , Ratas , Especies Reactivas de Oxígeno/metabolismo , Triglicéridos/metabolismo , Aumento de Peso
20.
Mol Cell Biochem ; 408(1-2): 235-43, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26160278

RESUMEN

UNLABELLED: Myocardial infarction leads to a reduction in nitric oxide (NO) bioavailability and an increase in reactive oxygen species (ROS) levels. This scenario has been shown to be detrimental to the heart. Recent studies have shown that thyroid hormone (TH) administration presents positive effects after ischaemic injury. Based on this, the aim of this study was to evaluate the effect of TH on NO bioavailability as well as on endothelial nitric oxide synthase (eNOS) expression after myocardial infarction. Male Wistar rats were divided into three groups: Sham-operated (SHAM), infarcted (AMI) and infarcted + TH (AMIT). During 26 days, the AMIT group received T3 and T4 (2 and 8 µg/100 g/day, respectively) by gavage, while SHAM and AMI rats received saline. After this, the rats underwent echocardiographic analysis were sacrificed, and the left ventricle was collected for biochemical and molecular analysis. STATISTICAL ANALYSIS: one-way ANOVA with Student-Newman-Keuls post test. AMI rats presented a 38% increase in ROS levels. TH administration prevented these alterations in AMIT rats. The AMIT group presented an increase in eNOS expression, in NOS activity and in nitrite levels. TH administration also increased PGC-1α expression in the AMIT group. In conclusion, TH effects seem to involve a modulation of eNOS expression and an improvement in NO bioavailability in the infarcted heart.


Asunto(s)
Infarto del Miocardio/tratamiento farmacológico , Óxido Nítrico Sintasa de Tipo III/metabolismo , Óxido Nítrico/metabolismo , Tiroxina/administración & dosificación , Triyodotironina/administración & dosificación , Animales , Modelos Animales de Enfermedad , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/metabolismo , Masculino , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Tiroxina/farmacología , Triyodotironina/farmacología
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