Inhibition of Azoxymethane-induced DNA Adduct Formation by Aloe arborescens var. natalensis

Abstract

To clarify the possible mechanisms of inhibition of azoxymethane (AOM)-induced aberrant crypt foci (ACF) in ‍the rat colorectum by freeze-dried whole leaves of Aloe arborescens var. natalensis (Kidachi aloe) (hereinafter referred ‍to as ALOE) and commercial crude aloin (Sigma A-0451; from Curacao aloe) (hereinafter ALOIN), we studied the ‍effects of ALOE and ALOIN on the formation of AOM-induced DNA adducts (O6-methylguanine; O6-MeG) in rats. ‍Male F344 rats (4 weeks old) were fed a basal diet, or experimental diets containing 5%ALOE or 0.25%ALOIN for ‍5 weeks. All rats were injected s.c. twice with 15 mg/kg AOM, once at the end of week 1, and once at the end of week ‍2. The animals were sacrificed 6 hours after the second injection to analyze DNA adducts (O6-MeG) in the colorectum. ‍Dietary administration of ALOE significantly inhibited the O6-MeG levels (50% reduction) compared with controls, ‍whereas the O6-MeG levels in the ALOIN-fed rats showed a tendency to decrease (by 30%), although not significantly. ‍In this study, we also measured the enzyme activity and mRNA level of cytochrome (CYP) 2E1, known to be responsible ‍for the activation of AOM, in rat liver. ALOE-fed rats showed significantly reduced CYP2E1 enzymatic activity ‍(27% reduction) compared with controls. On the other hand, the activity in ALOIN-fed rats tended to decrease by ‍11%, although not significantly. The CYP2E1 mRNA levels in ALOE- and ALOIN-fed rats were slightly reduced ‍(9.7% and 5.2%, respectively). These results may explain, at least in part, the previously observed inhibitory effects ‍of ALOE and ALOIN, especially ALOE on AOM-induced ACF formation in the rat colorectum.