Bioenergetic Status of the Intestinal and Hepatic Cells after Short Term Exposure to Fumonisin B1 and Aflatoxin B1

Abstract

Fumonisin B1 (FB1) and aflatoxin B1 (AFB1) are frequent contaminants of staple foods such as maize. Oral exposure to these toxins poses health hazards by disrupting cellular signaling. However, little is known regarding the multifaced mitochondrial dysfunction-linked toxicity of FB1 and AFB1. Here, we show that after exposure to FB1 and AFB1, mitochondrial respiration significantly decreased by measuring the oxygen consumption rate (OCR), mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). The current work shows that the integrity of mitochondria (MMP and ROS), that is the central component of cell apoptosis, is disrupted by FB1 and AFB1 in undifferentiated Caco-2 and HepG2 cells as in vitro models for human intestine and liver, respectively. It hypothesizes that FB1 and AFB1 could disrupt the mitochondrial electron transport chain (ETC) to induce mitochondrial dysfunction and break the balance of transferring H+ between the mitochondrial inner membrane and mitochondrial matrix, however, the proton leak is not increasing and, as a result, ATP synthesis is blocked. At the sub-toxic exposure of 1.0 µg/mL for 24h, i.e., a viability of 95% in Caco-2 and HepG2 cells, the mitochondrial respiration was, however, stimulated. This suggests that the treated cells could reserve energy for mitochondrial respiration with the exposure of FB1 and AFB1, which could be a survival advantage.

Lycopene alleviates multiple-mycotoxin-induced toxicity by inhibiting mitochondrial damage and ferroptosis in the mouse jejunum

“…37,41 It has also been reported that AFB1 disrupts the integrity of the mitochondria (MMP and ROS), inducing mitochondrial dysfunction and impairing mitochondrial respiration in undifferentiated Caco-2 cells, an in vitro model of the human intestine. 42 In the present study, co-exposure to ZEN, DON, and AFB1 caused mitochondrial damage, accompanied by the disruption of the mitochondrial morphological dynamics indicated by increase of mitochondrial fission and reduction of mitochondrial fusion. LYC is a common dietary supplement with antioxidant properties that also modulates the homeostasis of mitochondrial lipids.…”

Elucidating the combined toxicity of aflatoxin B1 and fumonisin B1 on HepG2 cells based on respirometry and transcriptome analyses

“…Furthermore, we applied three combinations (low-low, middle-middle, and high-high) as a binary mixture (MIX) of AFB1 and FB1 ( Table 1 ). These concentrations were applied based on the estimated exposure data derived from measuring the average of urinary biomarkers of AFB1 (0.5 µg/mL) and FB1(10 µg/mL) in humans, which were considered here in the current work as low exposure scenario (Chen et al 2022; Meneely et al 2018). This level was increased four folds to have a middle exposure scenario and eight folds as high exposure scenario to investigate the potential toxicity.…”

“…The tetrazolium salt (MTT) (Life Technologies Corporation, Eugene, OR, USA) assay, which is based on the cellular conversion of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide into formazan, was performed to determine the cell viability after the exposure to AFB1 and FB1 (Chen et al 2022). Briefly, HepG2 cells were seeded before the treatment in 96-well plates at a density of 20,000 per well for 24 h at 37 ⍰ in a sterilized incubator with a humidified atmosphere of 10 % CO 2 to allow cell adhesion.…”

“…The International Agency for Research on Cancer (IARC) classified AFB1 as a group 1 carcinogen due to the sufficient evidence of causing liver cancer in humans, while FB1 is classified as a class 2B carcinogen as the evidence of causing cancer is limited (IARC 2012). Other toxic effects of AFB1 and FB1 also include hepatotoxicity, nephrotoxicity, and embryotoxicity, immunotoxicity (Chen et al 2022).…”

“…Such toxicity could be induced by the loss of mitochondrial function creating a mitochondrial metabolic gridlock, such as the inhibition of mitochondrial respiration (Prakash et al 2022). The in vitro hepatotoxicity of AFB1 and FB1 has been reported in many studies using the HepG2 cells as the preferred liver model (Abdul and Chuturgoon 2021; Chen et al 2022; Singto et al 2020). Oxidative stress, inflammation, and mitochondrial dysfunction by targeting ROS, DNA, p53, and other signaling pathways have been documented as toxic mechanism of AFB1 (Li et al 2022).…”