Involvement of hepatic lipid droplets and their associated proteins in the detoxification of aflatoxin B(1) in aflatoxin-resistance BALB/C mouse

The highly potent carcinogen, Aflatoxin B(1), induces liver cancer in many animals including humans but some mice strains are highly resistant. This murine resistance is due to a rapid detoxification of AFB(1). Hepatic lipid droplets (LDs) ultimately impact the liver functions but their potential role in AFB(1) detoxification has not been addressed. This study describes the structural and functional impacts on hepatic LDs in BALB/C mice after exposure to 44 (low dose) or 663 (high dose) μg AFB(1)/kg of body weight. After 7 days, the liver of AFB(1)-dosed mice did not accumulate any detectable AFB(1) or its metabolites and this was associated with a net increase in gene transcripts of the AhR-mediating pathway. Of particular interest, the livers of high-dose mice accumulated many more LDs than those of low-dose mice. This was accompanied with a net increase in transcript levels of LD-associated protein-encoding genes including Plin2, Plin3 and Cideb and an alteration in the LDs lipid profiles that could be likely due to the induction of lipoxygenase and cyclooxygenase genes. Interestingly, our data suggest that hepatic LDs catalyze the in vitro activation of AFB(1) into AFB(1)-exo-8,9-epoxide and subsequent hydrolysis of this epoxide into its corresponding dihydrodiol. Finally, transcript levels of CYP1A2, CYP1B1, GSTA3 and EH1 genes were elevated in livers of high-dose mice. These data suggest new roles for hepatic LDs in the trapping and detoxifying of aflatoxins.