3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]
indole (Trp-P-1) is a group 2B
carcinogen characterized by the International Agency for Research on
Cancer (IARC) and great efforts have been taken to reduce
Trp-P-1 mutagenicity to humans. In this study, the effect of a reduction of
Trp-P-1 on intestinal absorption as a promising strategy was investigated. The data showed that when 20 mM
Trp-P-1 cotransported with 10 mM of
sodium carboxymethyl cellulose (CMC),
xanthan gum, or
carrageenan, the absorption rate of
Trp-P-1 was reduced by 31.5%, 49.5%, or 72.9% in MDCK-MDR1 cell monolayer, respectively; and 64.6%, 83.4%, or 64.1% in rat intestinal tissues, correspondingly. These 3
polysaccharides also reduced pharmacokinetic parameters, that is, Cmax , AUC0-t , and AUC0-∞ , after
Trp-P-1 was given to rats intragastrically. However,
gum arabic did not exhibit similar effects on
Trp-P-1 absorption in vitro or in vivo. The Ames test showed that these 3
polysaccharides reduced
Trp-P-1 mutagenicity to Salmonella typhimurium TA98, but
gum arabic did not. Isothermal titration calorimetry assay indicated that
Trp-P-1 interacted with these 3
polysaccharides. Thermodynamic study showed that the actual value of △H <0, but its absolute value greater than the corresponding value of T∆S, suggest a specific interaction between
Trp-P-1 and these 3
polysaccharides, probably through the hydrogen bond and/or ion interaction. Reduction of
Trp-P-1 intestinal absorption using
food additives could be one of the strategies to suppress Trp-P-1-induced
carcinogenesis in human.
PRACTICAL APPLICATION: