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Efeitos genómicos do Ftalato de dibutilo (DBP) a nível cardiovascular humano
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| Documento em Acesso Embargado até dia 23-11-2027. Tente solicitar cópia ao autor carregando no ficheiro | 26.03 MB | Adobe PDF |
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Abstract(s)
Um disruptor endócrino é “um agente que interfere com a síntese, secreção, transporte, ligação ou eliminação de hormonas naturais no organismo, responsáveis pela manutenção da homeostase, reprodução, desenvolvimento e/ou comportamento”, segundo a Agência de Proteção Ambiental dos Estados Unidos da América. Os ftalatos são diésteres do ácido ftálico, produtos químicos orgânicos sintéticos e são considerados disruptores endócrinos. O ftalato de dibutilo (DBP) é o ftalato de baixo peso molecular mais estudado, sendo encontrado em produtos de cuidados pessoais, brinquedos para crianças, produtos farmacêuticos, produtos alimentares, entre outros e serve para melhorar a flexibilidade e tornar os produtos poliméricos macios e maleáveis. Estudos recentes em animais sobre este composto revelaram que o DBP pode contribuir para o desenvolvimento de diversas anomalias a nível reprodutor, metabólico, nervoso e cardiovascular. No entanto, os seus impactos a nível humano ainda carecem de maior compreensão e investigação. Assim, o principal objetivo deste trabalho foi analisar os potenciais efeitos do DBP no sistema cardiovascular humano, utilizando artérias do cordão umbilical de grávidas sem patologias. Assim, analisámos os efeitos rápidos e de exposição prolongada (24h) do DBP sobre as células musculares lisas e a artéria umbilical humana. Os resultados obtidos indicam que o DBP não apresenta toxicidade nas células musculares lisas da artéria umbilical humana. Este ftalato parece promover o vasorelaxamento arterial de forma crescente com o aumento da sua concentração. Quanto aos ensaios genómicos, o DBP parece estar envolvido na ativação da via cGMP/NO/sGC/PKG e também parece interferir com os canais de Ca2+ do tipo L. Em suma, a exposição ao DBP parece perturbar as principais vias de contração e relaxamento das artérias, modificando a homeostase vascular e promovendo o desenvolvimento de doenças cardiovasculares.
An endocrine disruptor is “an agent that interferes with the synthesis, secretion, transport, binding or elimination of natural hormones in the body responsible for maintaining homeostasis, reproduction, development and/or behavior,” according to the US Environmental Protection Agency. Phthalates are phthalic acid diesters, synthetic organic chemicals, and are considered endocrine disruptors. Dibutyl phthalate (DBP) is the most widely studied low molecular weight phthalate. It is found in personal care products, children's toys, pharmaceuticals, food products, among others, and serves to improve flexibility and make polymeric products soft and malleable. Recent animal studies on this compound have revealed that DBP can contribute to the development of various reproductive, metabolic, nervous, and cardiovascular abnormalities. However, its impact on humans still needs to be better understood and researched. Thus, the main objective of this study was to analyze the potential effects of DBP on the human cardiovascular system, using umbilical cord arteries from pregnant women without pathologies. We therefore analyzed the effects of DBP on smooth muscle cells and the human umbilical artery after rapid and prolonged exposure (24 hours). The results obtained indicate that DBP is not toxic to human umbilical artery smooth muscle cells. This phthalate seems to promote arterial vasorelaxation to an increasing degree as its concentration increases. As for genomic assays, DBP seems to be involved in the activation of the cGMP/NO/sGC/PKG pathway and seems to interfere with L-type Ca2+ channels. In short, exposure to DBP seems to disturb the main pathways of contraction and relaxation of the arteries, modifying vascular homeostasis and promoting the development of cardiovascular diseases.
An endocrine disruptor is “an agent that interferes with the synthesis, secretion, transport, binding or elimination of natural hormones in the body responsible for maintaining homeostasis, reproduction, development and/or behavior,” according to the US Environmental Protection Agency. Phthalates are phthalic acid diesters, synthetic organic chemicals, and are considered endocrine disruptors. Dibutyl phthalate (DBP) is the most widely studied low molecular weight phthalate. It is found in personal care products, children's toys, pharmaceuticals, food products, among others, and serves to improve flexibility and make polymeric products soft and malleable. Recent animal studies on this compound have revealed that DBP can contribute to the development of various reproductive, metabolic, nervous, and cardiovascular abnormalities. However, its impact on humans still needs to be better understood and researched. Thus, the main objective of this study was to analyze the potential effects of DBP on the human cardiovascular system, using umbilical cord arteries from pregnant women without pathologies. We therefore analyzed the effects of DBP on smooth muscle cells and the human umbilical artery after rapid and prolonged exposure (24 hours). The results obtained indicate that DBP is not toxic to human umbilical artery smooth muscle cells. This phthalate seems to promote arterial vasorelaxation to an increasing degree as its concentration increases. As for genomic assays, DBP seems to be involved in the activation of the cGMP/NO/sGC/PKG pathway and seems to interfere with L-type Ca2+ channels. In short, exposure to DBP seems to disturb the main pathways of contraction and relaxation of the arteries, modifying vascular homeostasis and promoting the development of cardiovascular diseases.
Description
Keywords
Ftalato de Dibutilo Disruptor Endócrino Sistema Cardiovascular Artéria Umbilical Humana Células Musculares Lisas Vasculares Vasorelaxamento Dibutyl Phthalate Endocrine Disruptor Cardiovascular System Human Umbilical Artery Vascular Smooth Muscle Cells Vasorelaxation