Moreover, the cell death is critically dependent specifically on mitochondrial protein adduct formation [27, 28] and scavenging of mitochondrial reactive oxygen species (ROS) and peroxynitrite after the protein binding occurs effectively protects against cell death [2932]
Oxidation via CYP2E1 (5-10%) - TOXIC Creates NAPQI (N-acetyl-p-benzoquinone imine)the dangerous toxic metabolite INCREASES by 80% during pregnancy NAPQI measured at 43% HIGHER in first trimester when fetal brain is most vulnerable NAPQI must be immediately neutralized by glutathione When glutathione is depleted, NAPQI causes cellular damage Crosses placenta and damages fetal brain The Perfect Storm During Pregnancy Research reveals dramatic shifts in how pregnant women metabolize acetaminophen: Safe sulfation pathway DECREASES by 33% Toxic oxidation pathway INCREASES by 80% Glutathione levels DROP by 36-87% (when you need it most) Result: 43% MORE toxic NAPQI formed in first trimester Even though glucuronidation increases, it CANNOT compensate for the massive increase in toxic metabolite production combined with dramatically reduced glutathione reserves
Fujisawa, H., Nakayama, M., Haruyama, N., Fukui, A., Yoshitomi, R., Tsuruya, K., et al
This was determined by adding two standard deviations to the mean O
Downregulation of Kir4.1 inward rectifying potassium channel subunits by RNAi impairs potassium transfer and glutamate uptake by cultured cortical astrocytes
