Aflatoxin B1 Transfer and Metabolism in Human Placenta

Abstract

Aflatoxin B1 (AFB1), a common dietary contaminant, is a major risk factor of hepatocellular carcinoma (HCC). Early onset of HCC in some countries in Africa and South-East Asia indicates the importance of early life exposure. Placenta is the primary route for various compounds, both nutrients and toxins, from the mother to the fetal circulation. Furthermore, placenta contains enzymes for xenobiotic metabolism. AFB1, AFB1-metabolites, and AFB1-albumin adducts have been detected in cord blood of babies after maternal exposure during pregnancy. However, the role that the placenta plays in the transfer and metabolism of AFB1 is not clear. In this study, placental transfer and metabolism of AFB1 were investigated in human placental perfusions and in in vitro studies. Eight human placentas were perfused with 0.5 or 5microM AFB1 for 2-4 h. In vitro incubations with placental microsomal and cytosolic proteins from eight additional placentas were also conducted. Our results from placental perfusions provide the first direct evidence of the actual transfer of AFB1 and its metabolism to aflatoxicol (AFL) by human placenta. In vitro incubations with placental cytosolic fraction confirmed the capacity of human placenta to form AFL. AFL was the only metabolite detected in both perfusions and in vitro incubations. Since AFL is less mutagenic, but putatively as carcinogenic as AFB1, the formation of AFL may not protect the fetus from the toxicity of AFB1.

How does airway exposure of aflatoxin B1 affect serum albumin adduct concentrations? Evidence based on epidemiological study and animal experimentation

“…The AFB1 itself is not a potent toxin, and the bioactivation by liver CYP450 enzymes (Yen et al, 2009), particularly CYP3A4 and CYP1A2 to AFB1-8,9-epoxide, can form adducts with DNA and protein albumin (Partanen et al, 2010;Polychronaki et al, 2008), where its toxicity and carcinogenic effects are evident (Eaton and Gallagher, 1994). Although the AFB1 DNA adduct is more relevant with the HCC, we used AFB1 albumin adducts as biomarkers to assess the exposure.…”

Aflatoxin B1 and M1 in milk

“…The World Health Organization recommended the reduction of the AFLAM 1 levels in milk and dairy products to a minimum, in order to minimize the potential risk it poses. The toxic and carcinogenic effects have been extensively demonstrated in several species, especially in young animals [6,7]. There is, therefore, a great concern regarding the health of children, considering their high consumption of milk and dairy products, their low body weight and their great susceptibility to aflatoxins [5].…”

Aflatoxin B1 augments the synthesis of corticotropin releasing hormone in JEG-3 placental cells

“…The toxin given perorally is absorbed rapidly into the system of pregnant mice [3]. By perfusing the placenta after delivery, Partanen et al have demonstrated that aflatoxin B1 could pass through the organ and enter the fetal circulation [24]. These studies indicate that the toxin can be absorbed and transported across the placental tissue during pregnancy.…”