RESUMO
Di (2ethylhexyl) phthalate (DEHP), an environmental pollutant, is widely used as a plasticizer and causes serious pollution in the ecological environment. As previously reported, exposure to DEHP may cause thyroid dysfunction of the hypothalamicpituitarythyroid (HPT) axis. However, the underlying role of DEHP remains to be elucidated. The present study performed intragastrical administration of DEHP (150, 300 and 600 mg/kg) once a day for 90 consecutive days. DEHPstimulated oxidative stress increased the thyroid follicular cavity diameter and caused thyrocyte oedema. Furthermore, DEHP exposure altered mRNA and protein levels. Thus, DEHP may perturb TH homeostasis by affecting biosynthesis, biotransformation, biotransportation, receptor levels and metabolism through disruption of the HPT axis and activation of the thyroidstimulating hormone (TSH)/TSH receptor signaling pathway. These results identified the formerly unappreciated endocrinedisrupting activities of phthalates and the molecular mechanisms of DEHPinduced thyrotoxicity.
Assuntos
Dietilexilftalato/toxicidade , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Glândula Tireoide/efeitos dos fármacos , Animais , Poluentes Ambientais/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/crescimento & desenvolvimento , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Plastificantes/toxicidade , Ratos Wistar , Receptores da Tireotropina/genética , Receptores da Tireotropina/metabolismo , Receptores do Hormônio Liberador da Tireotropina/genética , Receptores do Hormônio Liberador da Tireotropina/metabolismo , Glândula Tireoide/crescimento & desenvolvimento , Glândula Tireoide/metabolismo , Hormônios Tireóideos/sangue , Hormônios Tireóideos/metabolismo , Fator Nuclear 1 de Tireoide/genética , Fator Nuclear 1 de Tireoide/metabolismo , Tireotropina Subunidade beta/genética , Tireotropina Subunidade beta/metabolismoRESUMO
Given the lack of research on the schoolchildren exposure to PM2.5-bound PHAs in northeast China, we investigated the effects of exposure to ambient benzo[b]fluoranthene (BbFA) and dibenz[a,h]anthracene (DahA) bound to PM2.5 on pulmonary ventilation dysfunction (PVD) and small airway dysfunction (SAD). PM2.5 samples at two schools (A and B) were collected, and the concentrations of PM2.5-bound 4-6-ring PAHs were analyzed. PVD and SAD were evaluated by pulmonary function tests in 306 students while urinary MDA and CRP levels were measured. The results confirmed that ambient PM2.5-bound 4-6-ring PHA levels were significantly higher and the PVD and SAD incidence in schools A and B were increased during the heating season. We found that PM2.5-bound BbFA, BkFA, BaP, and DahA levels were only correlated with SAD in schoolchildren; the correlation coefficients of BbFA and DahA were the highest effect estimates, possibly due to altered MDA levels. Therefore, this research enables us to better understand the effects of exposure to ambient PM2.5-bound PHAs on pulmonary function parameters. Our results also showed that identification of hazardous PM2.5-bound BbFA and DahA to health is crucial for preventing the respiratory-related diseases.