Oltipraz: a laboratory and clinical review

作者: Al B. Benson

DOI: 10.1002/JCB.240531041

关键词:

摘要: Oltipraz [5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione; RP 35972] is a synthetic, substituted 1,2-dithiole-3-thione previously used in humans as an antischistosomal agent. Cruciferous vegetables (e.g., Brussels sprouts, cabbage) contain several agents, including dithiolethiones, which appear to inhibit carcinogenesis; however, it unclear dietary compounds produce the protective effects. Animal studies have demonstrated that oltipraz potent inducer of Phase II detoxification enzymes, most notably glutathione-S-transferase (GST). Laboratory evaluations shown concentrations marked inhibition aflatoxin B1-induced hepatic tumorigenesis rats. Levels aflatoxin-DNA adducts, urinary aflatoxin-N7-guanine, and serum aflatoxin-albumin adducts decreased when biliary elimination aflatoxin-glutathione conjugants increased, thus providing predictive biomarkers measured chemopreventive effect. In other animal experiments, was found chemically induced carcinogenesis bladder, colon, breast, stomach, skin cancer models. addition, has been be non-mutagenic, radioprotector, chemoprotective agent against carbon tetrachloride acetaminophen toxicity. More recent rats suggest unsubstituted 1,2-dithiole-3-thiones may more effectively aflatoxin-induced induce electrophile enzymes. Multiple human clinical trials conducted using 1.0-4.5 gram doses over 1-3 days for treatment schistosomiasis. Phototoxicity precluded its use tropical areas. recently, 6 month I trial completed patients with resected colon polyps, or females first degree relatives breast cancer, were given oral daily at 125 mg 250 mg. The maximum tolerated dose = 1.0 microgram/mL achievable interpatient variability. A series small evaluating single up 28 (dosing range 1 mg/kg-3 mg/kg/day) also showed short t1/2 (4.1-5.3 hours), sustained steady state without variation after loading dose, increased urine consumption high-fat diet.(ABSTRACT TRUNCATED AT 400 WORDS)

参考文章(43)
NOëL LOZAC'H, JEAN VIALLE, THE CHEMISTRY OF THE 1,2-DITHIOLE RING The Chemistry of Organic Sulfur Compounds. pp. 257- 285 ,(1966) , 10.1016/B978-0-08-011062-2.50014-0
S. Orrenius, D. P. Jones, Functions of Glutathione in Drug Metabolism Springer, Berlin, Heidelberg. pp. 164- 175 ,(1978) , 10.1007/978-3-642-67132-6_20
Robert J. North, Down-Regulation of the Antitumor Immune Response Advances in Cancer Research. ,vol. 45, pp. 1- 43 ,(1985) , 10.1016/S0065-230X(08)60265-1
Thomas W. Kensler, Nancy E. Davidson, John D. Groopman, Bill D. Roebuck, Hans J. Prochaska, Paul Talalay, Chemoprotection by Inducers of Electrophile Detoxication Enzymes Antimutagenesis and Anticarcinogenesis Mechanisms III. ,vol. 61, pp. 127- 136 ,(1993) , 10.1007/978-1-4615-2984-2_12
Bandaru S. Reddy, Inhibitors of Carcinogenesis Biological Oxidation Systems. pp. 585- 595 ,(1990) , 10.1016/B978-0-12-584552-6.50009-4
Thomas W. Kensler, B. D. Roebuck, John D. Groopman, Patricia A. Egner, Patrick M. Dolan, Mechanism of Protection against Aflatoxin Tumorigenicity in Rats Fed 5-(2-Pyrazinyl)-4-methyl-1,2-dithiol-3-thione (Oltipraz) and Related 1,2-Dithiol-3-thiones and 1,2-Dithiol-3-ones Cancer Research. ,vol. 47, pp. 4271- 4277 ,(1987)
Diet in the Epidemiology of Cancer of the Colon and Rectum Journal of the National Cancer Institute. ,vol. 61, pp. 709- 714 ,(1978) , 10.1093/JNCI/61.3.709
A Case-Control Study of Large Bowel Cancer in Japan Journal of the National Cancer Institute. ,vol. 64, pp. 17- 22 ,(1980) , 10.1093/JNCI/64.1.17
Brian Coles, David J. Meyer, Brian Ketterer, Caroline A. Stanton, R. Colin Garner, Studies on the detoxication of microsomally-activated aflatoxin B1 by glutathione and glutathione transferases in vitro Carcinogenesis. ,vol. 6, pp. 693- 697 ,(1985) , 10.1093/CARCIN/6.5.693