Synergy among phytochemicals within crucifers: does it translate into chemoprotection?
Sommaire de l'article
Abstract: The association between cruciferous vegetables and cancer prevention has been linked to glucosinolate derivatives. These phytochemicals enhance endogenous detoxification, leading to inactivation of potential carcinogens before initiation occurs. Two derivatives, indole-3-carbinol (13C) and 1-cyano-2-hydroxy-3-butene (crambene) were shown in rats to induce a synergistic enhancement of detoxification enzyme activity. To follow up on these findings, a short-term carcinogenicity study using aflatoxin B1 (AFB(1)) was performed in which male F344 rats were fed diets supplemented with these 2 compounds alone or in combination. Groups included a negative control group (no AFB(1), crambene, or 13C), a crambene group (diet 0.150% crambene), an 13C group (diet 0.165% 13C), a high-dose group (diet 0.150% crambene, 0.165% 13C) a low-dose group (diet 0.030% crambene, 0.033% 13C), and a positive control group (AFB1 treatment only). AFB(1) was administered after 2 wk of dietary pretreatment. Liver sections were scored for lesions including karyornegaly, apoptosis, and biliary hyperplasia and evaluated for expression of the preneoplastic marker glutathione S-transferase-pi (GSTP). 13C and crambene groups were protected against AFB, toxicity whereas the low-dose group was not. The high-dose group had scores close to those of the negative controls. For log(10) transformed 2- and 3-dimensional GSTP data, the high-dose group demonstrated synergistic reduction in GSTP-positive area and an additive reduction in GSTP-positive volume compared with the crambene and 13C groups. The low-dose group had no effect. In conclusion, high combination dietary doses of 13C and crambene demonstrated enhanced protection from AFB(1). Low combination doses, as might be realistically in the diet, were not effective.