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Food Chem Toxicol ; 159: 112772, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34929351

RESUMO

Bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical, is commonly used as a plasticizer to manufacture various food packaging materials. Evidence has demonstrated that BPA disturbed bone health. However, few studies focused on the effect of BPA on osteocytes, making up over 95% of all the bone cells. Here, we reported that BPA inhibited the cell viability of MLO-Y4 cells, and increased apoptosis in a dose-dependent manner. Furthermore, BPA up-regulated protein expressions of speck-like protein containing CARD (ASC), NLRP3, cleaved caspase-1 (Casp-1 p20) and cleaved gasdermin D (GSDMD-N), and increased the ratios of interleukin (IL)-1ß/pro-IL-1ß and IL-18/pro-IL-18 in MLO-Y4 cells. BPA enhanced levels of lactate dehydrogenase (LDH), IL-1ß and IL-18 in culture supernatants. This pyroptotic death and the NLPR3 inflammasome activation were reversed by the caspase-1 inhibitor VX765 or the NLRP3 inflammasome inhibitor MCC950. Furthermore, BPA stimulated the production of intracellular reactive oxygen species (ROS), mitochondrial ROS (mtROS), elevated malondialdehyde (MDA) level and decreased superoxide dismutase (SOD) activity, which led to oxidative damage in MLO-Y4 cells. The ROS scavenger N-acetylcysteine (NAC) or the mitochondrial antioxidant Mito-TEMPO inhibited the NLPR3 inflammasome activation and pyroptotic death induced by BPA. Collectively, our data suggest that BPA causes pyroptotic death of osteocytes via ROS/NLRP3/Caspase-1 pathway.


Assuntos
Compostos Benzidrílicos/toxicidade , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Osteócitos/efeitos dos fármacos , Fenóis/toxicidade , Piroptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Animais , Caspase 1/metabolismo , Linhagem Celular , Camundongos , Osteócitos/metabolismo
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