Antiarthritic drugs containing thiol groups scavenge hypochlorite and inhibit its formation by myeloperoxidase from human leukocytes. A therapeutic mechanism of these drugs in rheumatoid arthritis?
We investigated the effect of antiarthritic drugs containing thiol groups, such as D-penicillamine, tiopronin (N-[2-mercaptopropionyl]glycine), sodium aurothiomalate, and aurothioglucose, on the chlorinating activity of myeloperoxidase purified from human leukocytes. Hypochlorite, the reactive product of the reaction catalyzed by myeloperoxidase, was effectively scavenged by these antiarthritic drugs, and in addition, D-penicillamine and tiopronin inhibited myeloperoxidase itself. The above-mentioned effects of these drugs were observed at concentrations that occur in the serum of rheumatoid arthritis patients treated with these agents. We suggest that the therapeutic effect of these antiarthritic drugs may be due to the protection of tissues against the reactive HOCI released by activated granulocytes at inflamed sites.
D000603:Amino Acids, Sulfur / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D006051:Aurothioglucose / Q000494:pharmacology; D003512:Cyclohexanones / Q000378:metabolism; D006052:Gold Sodium Thiomalate / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006997:Hypochlorous Acid / Q000096:biosynthesis / Q000378:metabolism; D007962:Leukocytes / Q000201:enzymology*; D010396:Penicillamine / Q000494:pharmacology*; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000097:blood*; D008625:Tiopronin / Q000494:pharmacology*
D000603:Amino Acids, Sulfur; D003512:Cyclohexanones; D006052:Gold Sodium Thiomalate; D006051:Aurothioglucose; D006997:Hypochlorous Acid; C006991:chlorodimedone; D006861:Hydrogen Peroxide; D008625:Tiopronin; D009195:Peroxidase; D010396:Penicillamine