9. Absorption of aflatoxins in small intestine

Aflatoxins are liposoluble compounds that are readily absorbed at the site of exposure (usually gastrointestinal tract) into the blood stream to liver where they are metabolized in the microsomal system to active or detoxified metabolites [63]. AFB1 may occur as free or unconjugated forms of primary metabolites. Water soluble conjugate metabolites bound covalently with cellular macromolecules and degradation/metabolic products of AFB1 adducts. These conjugates of AFB1 metabolites are excreted in the bile and consequently eliminated through feces. Water soluble conjugates and degradation or metabolic products of AFB1 macromolecule adducts and unconjugated AFB1 metabolites are excreted into general circulatory blood system. This results the systemic distribution of AFB1 to eggs or milk and body tissues [3].

AFs are known to alter the synthesis, absorption, and transport of lipids to extra-hepatic tissues. Liver fatty acid composition is drastically altered among birds with aflatoxicosis [43]. AFB1-8, 9 epoxide (formed by action of cytochrome P450 on AFB1) may cause significant increase in hepatic lipid peroxide level. Lipid peroxidation initiates to affect membrane integrity negatively; membrane bound enzyme activities which lead to cell lysis. The oxidative damage of cell/tissue occurs when the concentration of reactive oxygen species (O2�, H2O2, and OH�) predominates the antioxidant capability of cells. This may be the consequence of significant decrease in nonenzymatic antioxidants (e.g. glutathione, vitamin E, and vitamin C) and enzymatic antioxidants (e.g. catalase, glutathione peroxidase, superoxide dismutase). Superoxide dismutase shields cells from oxidative damage by metabolizing free radical superoxide (O2�) to H2O2 and O2�. The metabolically produced H2O2 can then be decomposed enzymatically with glutathione peroxidase (GSH-Px) and catalase. Glutathione peroxidase not only decomposes H2O2 but also can interact with lipid peroxidation. Reduced protein biosynthesis may be responsible for the decline in enzyme activities. Significantly lower glutathione peroxidase levels further intensify the toxic effects of AFs [24]. AFs promote free radical formation thus causing liver peroxidation which in turn results in antioxidant depletion, oxidative stress and apoptosis. All of these contribute to the development of malabsorption [64].

The metabolites such as AFB1-N7-Gua, AFM1, AFB1-mercapturic acid and serum AFs-albumin are also considered as AF biomarkers [65]. AFs show specific selection for guanine bases with a guanine or cytosine at the 5<sup>0</sup> base causing G ! T transversion [66]. Puisieux et al. [67] showed that the guanine at the third position of codon 249 of the p53 gene (a known mutational hotspot in HCC (hepatocellular carcinoma) was the site of modification by AFB1 (in human hepatocytes, about three folds mutations at the third base of codon 249) but neighboring guanines (247, 248 and 250) were also modified. About 20% of total AFB1 ingested remain in the body after a period of one week with a half-life in the plasma of 36.5 minutes, whereas M1 is almost excreted via urine within 48 hours [68]. Because there is a half-life of 20 days in serum albumin, the AFB1-albumin adduct can be used as an AF biomarker to check the chronic exposure within 1–2 months and is considered as an independent factor for advanced liver diseases in HCV-infected patients. The adduction levels of AFs with albumin by covalent bonding in the peripheral blood reflect AF exposure 2–3 months earlier depending on albumin half-life [66].
