Effects of aflatoxin B1, fumonisin B1 and their mixture on the aryl hydrocarbon receptor and cytochrome P450 1A induction

The aflatoxin B1‐fumonisin B1 toxicity in BRL‐3A hepatocytes is associated to induction of cytochrome P450 activity and arachidonic acid metabolism

“…In this work AFB 1 alone, and especially combined with FB 1 , increased the activity of PLA and CYP1A, being the latter in agreement with previous results published by Mary et al The interactive effects of the AFB 1 –FB 1 mixture on the CYP activity and ArAc metabolism induction may have been associated with the higher oxidative stress caused by the combined action of both mycotoxins, with the data indicating the nuclear transcription factor aryl hydrocarbon receptor (AhR) as being the probable mediator of such actions. Recently, Mary et al postulated that AFB 1 is an AhR agonist, as it increased the CYP1A activity and cyp1A transcription in the H4IIE rat hepatoma cell line, which was associated with an enhanced AhR activity (a primary regulator of cyp1A expression) in DR‐CALUX cell line. Moreover, the induction of other CYP subfamilies such as 3A by AFB 1 and FB 1, as well as the AFB 1 metabolization itself by CYP, might also contribute to the higher activity of this enzyme complex and consequent ROS generation.…”

“…However, due to the nonoxidative genotoxicity found in cells incubated with both toxins being greater than that observed in cells treated only with AFB 1 , this may be indicating an increased direct genotoxic activity (adduct formation) of the mixture, probably as a result of the major activation of CYP and the ArAc metabolism, which are the biochemical pathways involved in AFB 1 biotransformation . The results of this study are in agreement with those from a previous investigation, where the combination of AFB 1 and FB 1 resulted in increased CYP activity in H4IIE rat hepatoma cells by inducing specifically cyp1A expression and CYP1A activity, respect to the individual toxins . Although some studies have shown that FB 1 clastogenicity and genotoxicity were associated with an indirect mechanism involving oxidative damage to the human‐derived hepatoma (HepG2) cells, spleen mononuclear cells, and hepatocytes from rat, FB 1 did not increase chromosomal aberrations in BRL‐3A cells, even though the toxin worsened the cellular oxidative status.…”

“…On the other hand, the increased ArAc metabolism could be secondary to a major PLA2 expression caused by toxin‐stimulated AhR signaling, as previous genome microarray and real‐time quantitative RT‐PCR studies have demonstrated increased PLA2 mRNA levels upon AhR activation in mouse liver and hepatoma Hepa‐1c1c7 cells . Taken together, the preceding data suggest that the stronger induction effect of the AFB 1 –FB 1 mixture on the metabolic pathways studied in this study was probably provoked by a higher AhR activation, similarly to that observed in hepatic H4IIE cells …”

“…The choice of the higher concentration for FB 1 related to AFB 1 has been made on the basis of the maximum permissible levels of these mycotoxins in the international food standards and on the intestinal AFB 1 and FB 1 absorption (about 100 and 4%, respectively) after oral administration to rats. Moreover, the doses were selected on the basis of the literature data and previous studies …”

Curcumin nanoparticles loaded hydrogels protects against aflatoxin B1-induced genotoxicity in rat liver

“…Aflatoxin B 1 (AFB 1 ) is the most relevant mycotoxin worldwide because of its widespread occurrence, its high toxicity and its economic implications (Mary et al, 2015). AFB 1 is mainly produced by Aspergillus flavus and Aspergillus parasiticus and is commonly contaminant of cereals and oilseeds (Kensler et al, 2011).…”