RESUMO
Noise exposure represents the second most common cause of acquired sensorineural hearing loss and we observed that tumor necrosis factor α (TNFα) was involved in this context. The effect of Tnfα gene silencing on the expression profile related to the TNFα metabolic pathway in an experimental model of noise-induced hearing loss had not previously been studied. METHODS: Single ears of Wistar rats were pretreated with Tnfα small interfering RNA (siRNA) by trans-tympanic administration 24 h before they were exposed to white noise (120 dBSPL for three hours). After 24 h of noise exposure, we analyzed the electrophysiological threshold and the amplitude of waves I, II, III, and IV in the auditory brain response click. In addition, qRT-PCR was performed to evaluate the TNFα metabolic pathway in the ears submitted or not to gene silencing. RESULTS: Preservation of the electrophysiological threshold and the amplitude of waves was observed in the ears submitted to gene silencing compared to the ears not treated. Increased anti-apoptotic gene expression and decreased pro-apoptotic gene expression were found in the treated ears. CONCLUSION: Our results allow us to suggest that the blockade of TNFα by gene silencing was useful to prevent noise-induced hearing loss.
Assuntos
Inativação Gênica , Perda Auditiva Provocada por Ruído/genética , Perda Auditiva Provocada por Ruído/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Animais , Limiar Auditivo , Biomarcadores , Modelos Animais de Doenças , Suscetibilidade a Doenças , Potenciais Evocados Auditivos do Tronco Encefálico , Imunofluorescência , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Perda Auditiva Provocada por Ruído/diagnóstico , Interferência de RNA , RNA Interferente Pequeno/genética , RatosRESUMO
Monocytes circulate in the blood and migrate to inflammatory tissues, but their functions can be either detrimental or beneficial, depending on their phenotypes. In humans, classical monocytes are inflammatory cluster of differentiation (CD)14++CD16-CCR2++ cells originated from the bone marrow or spleen reservoirs and comprise ≥92% of monocytes. Intermediate monocytes (CD14++CD16+CCR2+) are involved in the production of anti-inflammatory cytokines [such as interleukin (IL)-10], reactive oxygen species (ROS), and proinflammatory mediators [such as tumor necrosis factor-α (TNF-α) and IL-1ß). Nonclassical monocytes (CD14+CD16++CCR2-) are patrolling cells involved in tissue repair and debris removal from the vasculature. Many studies in both humans and animals have shown the importance of monocyte chemoattractant protein-1 (MCP-1) and its receptor [chemokine receptor of MCP-1 (CCR2)] in pathologies, such as atherosclerosis and myocardial infarction (MI). This review presents the importance of these monocyte subsets in cardiovascular diseases (CVDs), and sheds light on new strategies for the blocking of the MCP-1/CCR2 axis as a therapeutic goal for treating vascular disorders.
Assuntos
Doenças Cardiovasculares/metabolismo , Quimiocina CCL2/metabolismo , Monócitos/metabolismo , Receptores CCR2/metabolismo , Animais , Anti-Inflamatórios/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/imunologia , Quimiocina CCL2/antagonistas & inibidores , Humanos , Ligantes , Monócitos/classificação , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Fenótipo , Receptores CCR2/antagonistas & inibidores , Transdução de SinaisRESUMO
OBJECTIVE: To analyze the effects of androgen therapy on the thyroarytenoid (TA) muscle, expression of androgen receptors (ARs) and hyaluronic acid (HA) concentration in the vocal folds (VFs) of adult female rats. METHODS: Twenty-one adult female Wistar rats were divided into experimental and control groups. The experimental group received weekly intramuscular injections of nandrolone decanoate for 9 weeks. Following euthanasia and dissection of the VFs, histomorphometric analysis of the TA muscle, immunohistochemical evaluation of ARs, and measurement of HA concentration using the ELISA-like fluorimetric method were performed. RESULTS: The experimental group exhibited a significantly larger mean fiber cross-sectional area in the TA muscle compared to the control group (434.3 ± 68.6 µm2 versus 305.7 ± 110.1 µm2; p = 0.029), indicating muscle hypertrophy. There was no significant difference in the number of muscle fibers. The experimental group showed higher expression of ARs in the lamina propria (62.0% ± 30.3% versus 22.0% ± 22.8%; p = 0.046) and in the TA muscle (45.0% ± 22.6% versus 18.3% ± 9.8%; p = 0.024). There was no significant difference in the concentration of HA. CONCLUSION: Exposure of adult female rats to androgen therapy resulted in hypertrophy of the TA muscle and increased expression of ARs in the VFs. The TA muscle seems to be the primary target of testosterone action in the VF, and the up-regulation of ARs might contribute to the persistent deepening of the voice. LEVEL OF EVIDENCE: NA Laryngoscope, 134:2316-2321, 2024.