Possible Interaction: Glutathione and Propylthiouracil

“However, 4 mM propylthiouracil did lead to a 50% increase in GSH reductase activity, and phenobarbital at 4 mM completely abolished GSH peroxidase and GSH reductase activity and led to a significant loss of viability.”

“Propylthiouracil PTU ) inhibited glutathione ( GSH ) S-transferase (EC 2.5.1.18) activity of rat spleens in a concentration dependent manner in vitro.”

“ Propylthiouracil pretreatment for 12 days enhanced the concentration of the following metabolites in the liver: ATP (1.5 fold), ATPase inhibitor protein (IF1) (4.5 fold), and reduced glutathione (1.3 fold), while the activity of the inhibitor protein increased 2 fold.”

“However, PTU severely decreased the glutathione (GSH) level.”

“ PTU inhibited the transferase activity by competing with GSH but the S-oxides of PTU acted by another mechanism.”

“Thus, oxidation of PTU leads to products which are potent inhibitors of GSH transferases.”

“Repeated administration of propylthiouracil PTU ) resulted in an increase in glutathione (GSH) transferases activity in rat liver cytosol toward various substrates except for epoxy(p-nitrophenoxy)propane.”

“In an in vitro system consisting of [(3)H]acetaminophen, liver microsomes from phenobarbital-pretreated rats, and an NADPH-generating system, we found that PTU had a dose-dependent additive effect with GSH on inhibition of acetaminophen covalent binding.”

“ Propylthiouracil inhibited the reaction and this inhibition could be overcome with increasing glutathione concentrations.”

“These studies suggest that propylthiouracil inhibits the GSH S-transferases in a unique fashion by competing with GSH as a substrate in reactions catalyzed by the enzymes.”