Oltipraz chemoprevention trial in Qidong, Jiangsu Province, People's Republic of China

Abstract

Oltipraz has been used clinically in many regions of the world as an antischistosomal agent and is an effective inhibitor of aflatoxin hepatocarcinogenesis in rats. This chemopreventive action of oltipraz results primarily from an altered balance in aflatoxin metabolic activation and detoxication. In 1995, a randomized, placebo-controlled, double-blind intervention was conducted in residents of Qidong, People's Republic of China, who are at high risk for exposure to aflatoxin and development of hepatocellular carcinoma. The major study objectives were to define a dose and schedule for oltipraz that would reduce levels of aflatoxin biomarkers in biofluids of the participants, and to further characterize dose-limiting side effects. Two hundred thirty-four healthy eligible individuals, including those infected with HBV, were randomized to receive either 125 mg oltipraz daily, 500 mg oltipraz weekly, or placebo. Blood and urine specimens were collected to monitor potential toxicities and evaluate biomarkers over the 8-week intervention and subsequent 8-week follow-up periods. Overall, compliance in the intervention was excellent; approximately 85% of the participants completed the study. Objective evaluation of adverse events was greatly facilitated by inclusion of a placebo arm in the study design. A syndrome involving numbness, tingling, and pain in the fingertips was the only event that occurred more frequently among the active groups (18 and 14% of the daily 125 mg and weekly 500 mg arms, respectively) compared to placebo (3%). These symptoms were reversible and could be relieved with non-steroidal antiinflammatory agents. A more complete understanding of the chemopreventive utility of oltipraz awaits completion of an assessment of the efficacy of oltipraz in modulating levels of aflatoxin biomarkers. J. Cell. Biochem. Suppls. 28/29:166-173. 1998 Wiley-Liss, Inc.

The Molecular Epidemiology of Chronic Aflatoxin Driven Impaired Child Growth

“…Thus both the formation of the reactive aflatoxin-epoxide and its detoxification are enhanced by oltipraz. Oltipraz was subsequently successfully used in a clinical trial in China during 1995 to demonstrate proof of principle in populations naturally exposed through diet [165]. The study had three groups (control, low dose intervention, and high dose intervention) and included an intervention period (8 weeks) and a clear-out period (8 weeks).…”

Mixed Inhibition of P450 3A4 as a Chemoprotective Mechanism against Aflatoxin B1-Induced Cytotoxicity with cis-Terpenones

“…Oltipraz is a potent inducer of metabolic phase II enzyme glutathione S -transferase (GST) and also a competitive inhibitor of P450 1A2 and 3A4 enzymes , . Although oltipraz showed excellent results against AFB1-induced cytotoxicity in animal studies, adverse effects were reported in patients – . The chemoprotection with dietary supplement chlorophyllin is achieved through the formation of complexes with AFB1 to reduce its bioavailability – .…”

cis-Terpenones as an Effective Chemopreventive Agent against Aflatoxin B1-Induced Cytotoxicity and TCDD-Induced P450 1A/B Activity in HepG2 Cells

“…The potent cytotoxicity of AFB1 is attributed to the covalent DNA modification by the exo -epoxide metabolite ( , ), resulting in liver damage and possibly hepatocellular carcinoma ( 4−8 ) . In past decades, several effective chemoprevention agents, including oltipraz and chlorophyllins, have been developed and showed promising results in clinical trials ( − ). Unfortunately, adverse effects were the major concern for oltipraz ( , ), whereas more mechanistic studies are required for chlorophyllins ().…”

“…In past decades, several effective chemoprevention agents, including oltipraz and chlorophyllins, have been developed and showed promising results in clinical trials ( − ). Unfortunately, adverse effects were the major concern for oltipraz ( , ), whereas more mechanistic studies are required for chlorophyllins (). Recently, the screening of natural products, such as extracts from algae (), onion bulbs (), and kola seeds (), has identified several alternatives as potential candidates against AFB1.…”