Herbal extracts differentially inhibit oxidative effects caused by the biotransformation of nifurtimox, nitrofurantoin and acetaminophen on rat liver microsomes

[摘要] Inflammation is a cellular defensive mechanism associated to oxidative stress. The administration of nitrofurantoin, nifurtimox and acetaminophen generates oxidative stress by their biotransformation through CYP450 system. The main adverse effect described for the first two drugs is gastrointestinal inflammation and that of the last, hepatitis. Therefore, standardised dry extracts from Rosmarinus officinalis, Buddleja globosa Hope, Cynara scolymus L., Echinacea purpurea and Hedera helix were tested to evaluate their capacity to decrease drug-induced oxidative stress. For that, rat liver microsomes were incubated with drugs in the presence of NADPH (specific CYP450 system cofactor) to test oxidative damage on microsomal lipids, thiols, and GST activity. All drugs tested induced oxidation of microsomal lipids and thiols, and inhibition of GST activity. Herbal extracts prevented these phenomena in different extension. These results show that antioxidant phytodrugs previously evaluated could alleviate drugs adverse effects associated to oxidative stress.

[学科分类] 植物学

[关键词] Inflamacixc3xb3n es un mecanismo de defensa el cual estxc3xa1 asociado a estrxc3xa9s oxidativo. La administracixc3xb3n de nitrofurantoxc3xadna;nifurtimox y paracetamol genera estrxc3xa9s oxidativo al metabolizarse a travxc3xa9s del sistema CYP450. El principal efecto adverso de los dos primeros fxc3xa1rmacos es inflamacixc3xb3n gastrointestinal y del tercero;hepatitis. Por lo tanto;utilizamos diversos extractos herbales para disminuir el estrxc3xa9s oxidativo inducido por estos fxc3xa1rmacos. Para esto se incubaron microsomas hepxc3xa1ticos de rata con dichos fxc3xa1rmacos en presencia de NADPH (cofactor especxc3xadfico del sistema CYP450) y se evaluxc3xb3 el daxc3xb1o oxidativo generado sobre los lxc3xadpidos;los tioles y la actividad GST microsxc3xb3mica. Todos los fxc3xa1rmacos indujeron oxidacixc3xb3n de los lxc3xadpidos y los tioles microsxc3xb3micos e inhibieron la actividad GST. Los extractos herbales previnieron estos fenxc3xb3menos oxidativos en diferente extensixc3xb3n. Estos resultados indican que fitofxc3xa1rmacos antioxidantes previamente evaluados;podrxc3xadan aliviar los efectos adversos asociados a estrxc3xa9s oxidativo de los fxc3xa1rmacos.