RESUMO
The high miscarriage rates observed in women smokers raises the possibility that chemicals in cigarette smoke could be detrimental to embryo development. Previous studies have established that polycyclic aromatic hydrocarbons (PAHs), transactivate the arylhydrocarbon receptor (AhR), leading to cell death. Herein we show that PAH exposure results in murine embryo cell death, acting as a potential mechanism underlying cigarette-smoking-induced pregnancy loss. Cell death was preceded by increases in Bax levels, activation of caspase-3 and decreased litter size. Chronic exposure of females to PAHs prior to conception impaired development, resulting in a higher number of resorptions. This embryonic loss could not be prevented by the disruption of Hrk, but was diminished in embryos lacking Bax. We conclude that exposure of early embryos to PAHs reduces the allocation of cells to the embryonic and placental lineages by inducing apoptosis in a Bax-dependent manner, thus compromising the developmental potential of exposed embryos.
Assuntos
Apoptose/efeitos dos fármacos , Embrião de Mamíferos/efeitos dos fármacos , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Proteína X Associada a bcl-2/fisiologia , 9,10-Dimetil-1,2-benzantraceno/farmacologia , Animais , Proteínas Reguladoras de Apoptose/fisiologia , Blastocisto/efeitos dos fármacos , Caspase 3/metabolismo , Feminino , Reabsorção do Feto/induzido quimicamente , Humanos , Tamanho da Ninhada de Vivíparos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Neuropeptídeos/fisiologia , Gravidez , Receptores de Hidrocarboneto Arílico/fisiologia , Fumar/efeitos adversosRESUMO
Sargassum hemiphyllum (SH) has long been used in Korean folk medicine for the therapeutic treatment of various allergic diseases. The effects of SH in previous experimental models, however, have been inconclusive. We studied the effects of methanol extract of SH on mast cells. Our experiments showed that SH significantly inhibited compound 48/80-induced histamine and beta-hexosaminidase release from rat peritoneal mast cells. SH inhibited interleukin (IL)-8 and tumor necrosis factor (TNF)-alpha release induced by phorbol 12-myristate 13-acetate and A23187 from HMC-1, and it also showed an inhibitory effect on the anti-dinitrophenyl IgE antibody-induced passive cutaneous anaphylaxis reaction. In addition, SH inhibited the increase of TNF-alpha-induced NF-kappaB protein levels, transcription factor of TNF-alpha from 293T cells. A period of 48 h exposure to SH had little effect on HMC-1 cell viability. Our results suggest that SH has an inhibitory effect on the atopic allergic reaction and thus this may be useful in the treatment of allergic inflammatory diseases, such as atopic dermatitis.
