Abstract
Aflatoxins are mutagenic hepatocarcinogenic fungal metabolites that contribute to chronic hepatitis B and C and viral cirrhosis, which can both evolve into hepatocellular carcinoma. Objective: To identify and quantify free aflatoxins and AFB1-N7-guanine (AFB1-N7-Gua) adducts (active carcinogen) in the urine of Mexican patients with chronic liver diseases. Methods: Urine samples from 210 Mexican patients with chronic liver diseases, hepatitis B or C, or viral cirrhosis and four control groups: 1) patients with alcoholic cirrhosis, 2) patients with no hepatic diseases, 3) patients with kidney failure, and 4) healthy persons, were analyzed for free aflatoxins and AFB1-N7-Gua adducts by Inhibitory Indirect ELISA and high performance liquid chromatography, and both methods produced similar results (R2=0.90). A questionnaire regarding foods with high risk of containing aflatoxins was applied to relate diet and disease. Results: Aflatoxin-positive samples were found from patients in the following groups: hepatitis B (50%), viral cirrhosis (26%), hepatitis C (16.6%), alcoholic cirrhosis (10%), healthy (10%), kidney failure (0.47%), and chronic nonhepatic diseases (0%), with R2=0.95. Risk groups had more AFB1-N7-Gua adducts than controls. High performance liquid chromatography identified free AFB1 (exposure), types M1 and P1 (detoxification metabolites), and Inhibitory Indirect ELISA quantified AFB1-N7-Gua adduct (a DNA repair biomarker). High-risk foods related (P≤0.001) to hepatic diseases were maize, oil seeds, and dairy products. Conclusion: Mexican patients with chronic liver diseases exhibited high concentrations of aflatoxins and Aflatoxin-N7-Gua adducts, both of which showed high exposure and the last are significant biomarkers for the risk of liver diseases that predispose patients to liver cancer.
Highlights
Aflatoxins (AFs) are secondary metabolites and polyketides of a group of dihydrobisfuran-coumarins, which are divided into two subgroups depending on their chemical structure
The bisfurancoumarin-cyclopentanones include AFs, which are further categorized into groups labeled B, Q, P and M (AFB1, AFB2, AFB2a, AFM1, AFM2, AFM2a, AFQ1, AFP1), and aflatoxicol (AFL), which corresponds to the subgroup of bisfuran-coumarin-lactones, in which the AFs in the G groups G (AFG1, AFG2, AFG2a) are placed [1,2,3]
This study focused on collecting Aflatoxin B1 (AFB1)-N7-Gua adducts in urine because this method is non-invasive and because chronic liver diseases are not treated through surgical operations in which samples could be collected; the collection of sampling tissues is possible only by biopsies and necropsies, and urine is easier to obtain
Summary
Aflatoxins (AFs) are secondary metabolites and polyketides of a group of dihydrobisfuran-coumarins, which are divided into two subgroups depending on their chemical structure. AFs are the most toxic of the known mycotoxins and are a significant risk factor for liver and kidney cancer [10] These potent mutagens and carcinogens [11] are directly implicated in causing or exacerbating liver diseases such as hepatitis B (HBV) [12] and C (HCV) [13], cirrhosis [14,15], various cancers [11,16,17], and primary Hepatocellular Carcinoma (HCC) [18,19], as well as teratogenicity [20], undernutrition, micronutrient malabsorption [10], immune dysfunction [21,22], stunting [23] and protein deficiency syndromes
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