Nitroreduction and formation of hemoglobin adducts in rats with a human intestinal microflora.

Abstract

In the covalent binding of nitroarenes to macromolecules, nitroreduction is an important step. The intestinal microflora represents an enormous potential of bacterial nitroreductase activity. As a consequence, the in vivo nitroreduction of orally administered nitroarenes is primarily located in the intestine. In this study, we have investigated the nitroreduction of 2-nitrofluorene (2-NF) by a human microflora in female Wistar rats. Germ-free (GF) rats were equipped with a bacterial flora derived from human feces. Nontreated GF rats and GF animals equipped with a conventional rat flora were used as controls. The composition of the human and the conventional microflora isolated from the rats were consistent with the microflora of the administered feces. In the rats receiving only sunflower seed oil, no adducts were detected. The animals equipped with a human or rat microflora that received 2-aminofluorene (2-AF) formed 2-AF hemoglobin (Hb)-adducts at average levels (mean +/- SEM) of 5.3 +/- 0.3 and 6.7 +/- 0.7 mumole/g Hb, respectively. After 2-NF administration, the adduct levels were 0.022 +/- 0.003 and 0.043 +/- 0.010 mumole/g Hb, respectively. In the GF rats, an adduct level of 0.57 +/- 0.09 was determined after 2-AF administration and no adducts were detected after 2-NF administration. The results show that nitroreduction by an acquired human intestinal microflora and subsequent adduct formation can be studied in the rat in vivo.

Evaluation of mutagenic and antimutagenic potential of stem bark aqueous extracts of eight trees by the bacterial reverse mutation assay

“…In the Ames assay, 2-NF nitroreduction followed by O-acetylation is a critical pathway that leads to mutagenesis [20,21]. Paul et al [22] showed the possibility of 2-NF nitroreduction by human microflora in female Wistar rats. It has also been proposed that the mutagenicity of 2-NF in bacterial cells may be partly connected to oxidative stress.…”

In Vivo Effects of Pichia Pastoris-Expressed Antimicrobial Peptide Hepcidin on the Community Composition and Metabolism Gut Microbiota of Rats

“…The increase of fecal nitroreductase activity in female rats might result from the change of gut microbiota as well. Nitroreductase is one of the procarcinogenic enzymes and the gut microbiota represents an enormous potential of bacterial nitroreductase activity [ 34 ]. The increase of nitroreductase results in more transformation of nitro-aromatic compounds to aromatic amines, which are harmful to the health of animals or human beings.…”