Fecal and urinary excretion of aflatoxin B₁ metabolites (AFQ₁, AFM₁ and AFB‐N⁷‐guanine) in young Chinese males

Abstract

Our study was designed to assess the fecal and urinary excretion of 3 aflatoxin B 1 (AFB 1 ) metabolites, aflatoxins M 1 (AFM 1 ) and Q 1 (AFQ 1 ) and aflatoxin B 1 -N 7 -guanine (AFB-N 7 -guanine) that are produced by the predominant forms of cytochrome P450 enzymes responsible for the biotransformation of AFB 1 . Fecal and urinary AFM 1 , AFQ 1 and urinary AFB-N 7 -guanine were assessed in 83 young Chinese males selected from a larger population (n = 300) based on detectable urinary AFM 1 . The concentration of fecal AFQ 1 (median 137 ng/g fresh weight, IQR 9.1 to 450) was approximately 60 times higher than that of AFM 1 (2.3 ng/g, IQR 0.0 to 7.3). In urine, the median AFQ 1 was 10.4 ng/ml (IQR 3.4 to 23.3), and the median AFM 1 and AFB-N 7 -guanine 0.04 ng/ml (IQR 0.01 to 0.33) and 0.38 ng/ml (IQR 0.0 to 2.15), respectively. A subgroup (n = 14) with hepatitis B virus (HBV) infection had significantly higher fecal concentrations of AFQ 1 ( p = 0.043) and AFM 1 ( p = 0.001) than those who were hepatitis B-virus antigen (HBsAg) negative, and the respective differences in urinary AFQ 1 and AFM 1 concentrations approached statistical significance ( p = 0.054, p = 0.138). Our study demonstrates that AFQ 1 is excreted in urine and feces at higher levels than AFM 1 , and feces are an important route of excretion of these AFB 1 metabolites. AFQ 1 should be further assessed for its predictive value as a marker for exposure and risk of dietary aflatoxins. The most serious health effect of dietary exposure to aflatoxins is hepatocellular carcinoma. The etiology of this disease also involves chronic infection with hepatitis B and C viruses (HBV and HCV), and a significant synergistic interaction between aflatoxin exposure and hepatitis B virus has been reported. 2,3After oral uptake AFB 1 is efficiently absorbed and metabolized prior to excretion by fecal and urinary routes (Fig. 1). Absorbed AFB 1 and its metabolites are excreted in urine, while elimination to feces is a route for both the unabsorbed AFB 1 and biliary excretion of metabolites formed from the absorbed toxin. Animal studies have shown that under normal conditions 50% of the orally administered dose of AFB 1 is quickly absorbed from the duodenal region of the small intestine 4 and enters the liver through the hepatic portal blood supply.5 AFB 1 is concentrated in the liver and to a lesser extent in kidney, 6 and it is also found in the mesenteric venous blood as free AFB 1 or its water-soluble metabolites.Members of the cytochrome P450 (CYP) enzyme family, CYP1A2, CYP3A4 and CYP2A6 have been shown to be responsible for the metabolism of the absorbed aflatoxins 7,8 (Fig. 1). These enzymes convert AFB 1 to its carcinogenic form, AFB-8,9-epoxide, which is covalently bound to DNA 9 and serum albumin, 10 forming aflatoxin B 1 -N 7 -guanine (AFB-N 7 -guanine) and lysine adducts, respectively. These enzymes also oxidize AFB 1 to various other derivatives, including aflatoxin M 1 (AFM 1 ), aflatoxin Q 1 (AFQ 1 ), aflatoxin P 1 as well as a reduced aflatoxin species...

Lactobacillus rhamnosus Strain GG Reduces Aflatoxin B 1 Transport, Metabolism, and Toxicity in Caco-2 Cells

“…This was surprising, as the culture model included 1,25(OH) 2 D 3 to upregulate CYP 3A4 expression (35). The lack of detection of this metabolite may reflect the detection limit for AFQ 1 , which is considerably (approximately 100-fold) higher than that for AFM 1 (27). However, the fact that toxicity of AFB 1 was observed only for 1,25(OH) 2 D 3 -pretreated cells is strongly supportive of an increased CYP 3A4 activity and generation of the highly reactive aflatoxin epoxide.…”

A direct assessment of mycotoxin biomarkers in human urine samples by liquid chromatography tandem mass spectrometry

“…1 The error bars represent the standard deviations obtained from the five different individual samples. Calibration range, same as those used to 24 determine the method linearity (see Table 2). …”

“…Levels of AFQ 1 were strongly correlated (r = 0.673) with detected levels of AFB 1 -N7Guanine adduct (AFB 1 -N7Gua), a strong biomarker for cancer effect. Consequently, AFQ 1 was suggested as a predictive marker for AFB 1 exposure [24]. However, the use of this metabolite is strongly compromised due to the lack of commercial standards.…”

Lactobacillus rhamnosus Strain GG Modulates Intestinal Absorption, Fecal Excretion, and Toxicity of Aflatoxin B 1 in Rats

“…Extraction of fecal samples was modified from a method developed in our laboratory (17). The samples were mixed with 2.5 volumes of 0.2 M sodium acetate in 10% NaCl, and aliquots (2 ml) were spiked with aflatoxin G 2 (AFG 2 ) (18.6 pmol/sample) as an internal standard and centrifuged (3,000 ϫ g; 15 min; 4°C).…”

“…Aliquots (0.5 ml) were spiked with AFG 2 (9.3 pmol/sample), and the aflatoxin residues were isolated and concentrated as mentioned above. Reverse-phase HPLC conditions were used as described previously (17). AFB 1 and AFM 1 levels in urine and feces were corrected for intersample variation using AFG 2 as an internal standard and calculated from a standard curve in urine and feces as total daily excretion.…”