Polysaccharides Reduce Absorption and Mutagenicity of 3-Amino-1,4-Dimethyl-5H-Pyrido[4,3-b]Indole In Vitro and In Vivo.
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
1.This study provides insightful information for the food industry how gum arabic, xanthan gum, kappa carrageenan, and sodium carboxymethyl cellulose affect the absorption of Trp-P-1. 2.This study also provides novel information regarding a better formulation for meat products to reduce Trp-P-1 absorption.
['Luo|Lingying|L|', 'Bai|Yun|Y|', 'Zhou|Guanghong|G|http://orcid.org/0000-0002-8960-2141']
D000818:Animals D002243:Carbolines D002273:Carcinogens D007408:Intestinal Absorption D007413:Intestinal Mucosa D008297:Male D009152:Mutagenicity Tests D009153:Mutagens D011134:Polysaccharides D051381:Rats D012486:Salmonella typhimurium
3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole sodium carboxymethyl cellulose xanthan gum carrageenan gum arabic