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J Toxicol Environ Health A ; 65(5-6): 407-18, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11936221

RESUMO

The effects of 15-deoxy-delta12,14-prostaglandin J2 (15-deoxy PGJ2) on ochratoxin A (OTA)-induced neurotoxicity and on the activation of transcription factors activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappaB) were investigated in cultured rat embryonic midbrain cells. Twelve-day rat embryo midbrain cells were cultured for 48 h. OTA (0.5 or 1 microg/ml) and/or 1.5-deoxy PGJ2 (0.5 microM) were then added for 48 h. Cell number and neurite outgrowth were determined to assess the neurotoxicity of OTA. AP-1 and NF-kappaB activation was determined by gel mobility shift assay after 3 h of exposure to OTA and/or 15-deoxy PGI2. OTA caused concentration-dependent reductions in neurite outgrowth and cell number, and induced AP-1 and NF-kappaB activation. Cotreatment with 15-deoxy PGJ2 (0..5 microM) blocked OTA-induced decrease in neurite outgrowth and cell number and inhibited AP-1 and NF-kappaB activation. 15-Deoxy PGJ2 (0.5 microM) caused the expression of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in the cells. Results show that 1.5-deoxy PGJ2 blocked OTA-induced neurotoxicity by inhibiting AP-1 and NF-kappaB activation in cultured rat embryonic midbrain cells.


Assuntos
Carcinógenos/toxicidade , Fatores Imunológicos/farmacologia , Ocratoxinas/toxicidade , Prostaglandina D2/análogos & derivados , Prostaglandina D2/farmacologia , Fator de Transcrição AP-1/biossíntese , Animais , Técnicas de Cultura de Células , Divisão Celular , Interações Medicamentosas , Mesencéfalo/citologia , Mesencéfalo/embriologia , NF-kappa B/biossíntese , Neuritos/efeitos dos fármacos , Ratos , Fator de Transcrição AP-1/farmacologia
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