Autor(es)

Barbetta, Maike Felipe Santos ; Baviera, Giovanni Stoppa ; Perovani, Icaro Salgado ; Duarte, Leandro Oka ; de Oliveira, Anderson Rodrigo Moraes

• Tipo de documento: Artigo Científico
• Fonte: ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY; v. 118, p. 10-pg., 2025-09-01.

Resumo

Penconazole (PEN) is a chiral triazole fungicide widely used in vineyards. Despite its detection in human urine and documented toxicological effect in non-targeted organisms, data on PEN's effects in humans is scarce. This study investigated the in vitro inhibitory effects of racemic PEN and its isolated enantiomers on major CYP450 isoforms using human liver microsomes. PEN inhibited all tested CYP450 enzymes, with CYP1A2, CYP2C9, and CYP3A4/5 being the most sensitive (Ki values: 0.73-8.1 mu mol L-1). Notably, the R-(+)-PEN enantiomer exhibited stronger inhibition of CYP1A2 and CYP2D6, indicating enantioselective interactions. In vivo extrapolation indicated that PEN could significantly inhibit CYP3A4/5, the primary isoform involved in metabolism of xenobiotics, and should not be overlooked. These findings provide critical insights into human toxicity of PEN and contribute to understanding its toxicological and environment impact, especially from an enantioselective perspective in drug-pesticide interactions. (AU)

• Processo FAPESP: 18/07534-4 - Desenvolvimento de métodos cromatográficos/eletroforéticos para posterior aplicação em estudos in vitro de inibição enzimática e predição de interações medicamentosas de praguicidas quirais - Fase 2
• Beneficiário: Anderson Rodrigo Moraes de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 21/10098-4 - Avaliação enantiosseletiva in vitro do efeito de praguicidas quirais sobre as principais enzimas do citocromo P450 de humanos envolvidas no metabolismo de fármacos: correlação in vitro-in vivo e predição de interação praguicida-fármaco
• Beneficiário: Anderson Rodrigo Moraes de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/50945-4 - INCT 2014: Instituto Nacional de Tecnologias Alternativas para Detecção, Avaliação Toxicológica e Remoção de Micropoluentes e Radioativos
• Beneficiário: Maria Valnice Boldrin
• Modalidade de apoio: Auxílio à Pesquisa - Temático