A COMPARATIVE STUDY ON THE EFFECT OF OLTIPRAZ ON GLUTATIDONE METABOLISM IN CULTURED MOUSE BEPATOCYTES AND SffiSTOSOMA MANSONI

Abstract

Oltipraz (OPZ), a dithiolthione derivative, was originally introduced . as an investigational drug for treatment of schistosomiasis. The mechanism of its schistosomicidal action was thought to be related to perturbation of reduced glutathione (GSH) metabolism. Although single oral doses of OPZ have achieved cure rates of more than 90% in field trials, it has been withdrawn from further trials because of its adverse side effects of phototoxicity that prevented its • use in tropical areas. Subsequently, OPZ was shown to possess c_hemopreventive activity against different classes of carcinogens in rodents. Perturbation of the antioxidant defense system has been implicated both in cancer development in mammals and in the susceptibility of Schistosoma mansoni worms to eradication by the drug. OPZ has . the unique characteristic of producing opposite effects on GSH and its related enzymes in parasites and in mammals. While schistosomicidal doses of OPZ cause depletion of GSH from the parasite, much lower doses (5- 10% of the schistosomicidal doses) resulted in increased GSH levels in mammalian _cells. The broad range of OPZ anti-carcinogenic activity coupled with its low toxicity in mammals, when administered in the low doses for prevention of cancer development, made it a promising