SHORT COMMUNICATION: Evaluation of the post-initiation effects of oltipraz on aflatoxin B₁-induced preneoplastic foci in a rat model of hepatic tumorigenesis

Abstract

Previous studies have demonstrated that ingestion of 5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione (oltipraz) during the aflatoxin B1 (AFB1) treatment phase completely prevented hepatic cancer. In this study we evaluated the effect of feeding oltipraz during the post-AFB1 treatment phase. Fifty-five male F344 rats were divided into five groups. All rats were gavaged with 25 micrograms AFB1/rat, five times a week for two successive weeks. The rats were fed the oltipraz-supplemented diet according to three different feeding regimes: during the AFB1 treatment phase (1 week prior to, during and 1 week after the last gavage with AFB1); during the post-treatment phase; or throughout the entire time of the experiment. Phenobarbital-supplemented diet was fed during post-treatment phase to one group and this was used as a positive control for the promotion of AFB1-induced focal growth. The burden of putative, preneoplastic, hepatic glutathione S-transferase P-positive foci was evaluated at 13 weeks after the AFB1 treatment phase. As seen previously, oltipraz fed during the AFB1 treatment phase significantly inhibited focal development, i.e. the volume percent of the liver occupied with foci was reduced by 87%. Oltipraz when fed during the post-treatment phase neither inhibited nor enhanced focal development.

Prevention of hepatocarcinogenesis with phosphatidylcholine and menaquinone-4: In vitro and in vivo experiments

“…Moreover, GST-P-positive foci are recognized to be putative preneoplastic lesions [17,22,33]. In the present study, our results clearly showed inhibition by KaytwoN or PC alone on the number and relative area of GST-P-positive preneoplastic liver lesions induced in rats by DEN plus PB.…”

The emerging role of the Nrf2–Keap1 signaling pathway in cancer

“…There is no evidence to date suggesting that the agents used to activate the Nrf2 pathway have adverse impacts on tumor growth. Administration of oltipraz in rats, for example, did not affect hepatic tumor yield or burden, and similar results were seen with other Nrf2 activators (Maxuitenko et al 1993). Therefore, transient activation of Nrf2 in cells with an intact Nrf2-Keap1 axis by pharmacological activators is safe for the purpose of chemoprevention.…”

Chemopreventive effects of 2-(allylthio)pyrazine on hepatic lesion, mutagenesis and tumorigenesis induced by vinyl carbamate or vinyl carbamate epoxide

“…Of particular interest is the antischistosomal drug oltipraz, which exhibits striking chemopreventive activities against chemically induced carcinogenesis in various animal models (17)(18)(19)(20). It also ameliorates hepatic damage induced by aflatoxin B 1 , acetaminophen and carbon tetrachloride (28)(29)(30).…”

“…These compounds inhibit expression of some cytochrome P450 isoforms (8)(9)(10)(11), particularly P450 2E1 (CYP2E1*), and also induce such phase II detoxification enzymes as glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase (3,(10)(11)(12)(13)(14). Besides naturally occurring organosulfur compounds, certain synthetic sulfur-containing substances including oltipraz and sulindac have been shown to exert striking chemopreventive properties against experimental carcinogenesis in many animal tumor models (15)(16)(17)(18)(19)(20).…”