Oltipraz [5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione] protects against aflatoxin B1-induced hepatocarcinogenesis in rats when fed before and during carcinogen exposure; however, such an exposure-chemoprotection intervention paradigm is not directly relevant to most human populations. To model and assess the possible efficacy of short term interventions targeted at individuals at risk for su...

OBJECTIVE To determine whether oltipraz (4-methyl-5-pyrazinyl-3H-1,2-dithiole-3-thione) protects against oxidative injury in cultured human retinal pigment epithelial (hRPE) cells. METHODS Primary cultured hRPE cells were incubated with various concentrations of oltipraz followed by treatment with the chemical oxidant tert-butylhydroperoxide (tBH). Cell viability was assessed by release of la...

Aflatoxin, which leads to formation of carcinogen-DNA adducts as well as oxidized DNA, is a well-known risk factor for development of hepatocellular carcinoma. The aim of the present study was to investigate if the chemopreventive agent oltipraz had an effect on DNA oxidation measured as oxidized guanine derivatives in urine among healthy individuals living in a region of China at high risk of ...

The cancer chemopreventive actions of oltipraz (4-methyl-5-[2-pyrazinyl]-1,2-dithiole-3-thione) have been primarily associated with the induction of phase 2 detoxifying enzymes through transcriptional activation of the antioxidant response element (ARE) in the promoter regions of these genes. The transcription factor Nrf2 has been shown to bind to and activate AREs. Previously, we demonstrated ...

BACKGROUND Residents of Qidong, People's Republic of China, are at high risk for development of hepatocellular carcinoma, in part due to consumption of foods contaminated with aflatoxins, which require metabolic activation to become carcinogenic. In a randomized, placebo-controlled, double-blind phase IIa chemoprevention trial, we tested oltipraz, an antischistosomal drug that has been shown to...

Oltipraz [5-(2.pyrazinyl)-4-methyl-1,2-dithiole-3-thionej is a synthetic dithiolethione with chemopreventive activity against carcinogen-induced neoplasia of liver, lung, and colon in several animal model systems. Protection from tumor formation is associated with elevation of Phase H enzymes, including glutathione (GSH) transferase and NAD(P)H:quinone oxidoreductase (DT-diaphorase) in experime...

2-Amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mutagenic and carcinogenic heterocyclic amine present in pyrolysate products of meat and fish and has been shown to induce tumors in the colon, mammary gland, and possibly lymphatic system. Experiments were designed to examine the lymphoma-inducing capacity of PhIP and to test the inhibitory effects of oltipraz on PhIP-induced lymphoma...

BACKGROUND AND PURPOSE The incidence of diabetes mellitus is increased in patients with liver cirrhosis. Oltipraz is currently in trials to treat patients with liver fibrosis and cirrhosis induced by chronic hepatitis types B and C and is primarily metabolized via hepatic cytochrome P450 isozymes CYP1A1/2, 2B1/2, 2C11, 2D1 and 3A1/2 in rats. We have studied the influence of diabetes mellitus on...

OBJECTIVE To determine the effects of topical administration of 20% oltipraz solution on histomorphometrical and stereological aspects of skin tissue in full thickness skin wounds in laboratory rats. METHODS Thirty-six male Wistar portion rats (220±20 g) were randomly divided into three groups (n=12). On the first day of experimentation, a 1-cm2 circular wound was made on the posterior surfac...

Phase II detoxifying enzymes like NAD(P)H (quinone acceptor)oxidoreductase1 (NQO1), glutathione S-transferases (GST), and UDP-glucuronyltransferases (UGT) may play an important role in preventing carcinogen-induced cancers. Inducers of these enzymes have been shown to inhibit carcinogen-induced colon tumors in rat and mouse models. However, it has not been clearly demonstrated that NQO1 contrib...