ABSTRACT
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.
Subject(s)
Cardiomegaly/genetics , Hyperthyroidism/genetics , Interleukin-10/genetics , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Toll-Like Receptor 4/genetics , Animals , Apoptosis/drug effects , Body Weight/drug effects , Cardiomegaly/chemically induced , Cardiomegaly/metabolism , Cardiomegaly/pathology , Gene Expression Regulation , Heart/drug effects , Heart/physiopathology , Heart Ventricles/drug effects , Heart Ventricles/pathology , Hyperthyroidism/chemically induced , Hyperthyroidism/metabolism , Hyperthyroidism/pathology , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Interleukin-10/metabolism , Male , Mitochondria/drug effects , Mitochondria/metabolism , Mitochondria/pathology , Myeloid Differentiation Factor 88/genetics , Myeloid Differentiation Factor 88/metabolism , NF-kappa B/genetics , NF-kappa B/metabolism , Organ Size/drug effects , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats , Rats, Wistar , Signal Transduction , Thyroid Gland/drug effects , Thyroid Gland/pathology , Thyroxine/administration & dosage , Thyroxine/blood , Toll-Like Receptor 4/metabolism , Triiodothyronine/blood , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolismABSTRACT
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.