Discovering the Protective Effects of Quercetin on Aflatoxin B1-Induced Toxicity in Bovine Foetal Hepatocyte-Derived Cells (BFH12)

Abstract

Aflatoxin B1 (AFB1) induces lipid peroxidation and mortality in bovine foetal hepatocyte-derived cells (BFH12), with underlying transcriptional perturbations associated mainly with cancer, cellular damage, inflammation, bioactivation, and detoxification pathways. In this cell line, curcumin and resveratrol have proven to be effective in mitigating AFB1-induced toxicity. In this paper, we preliminarily assessed the potential anti-AFB1 activity of a natural polyphenol, quercetin (QUE), in BFH12 cells. To this end, we primarily measured QUE cytotoxicity using a WST-1 reagent. Then, we pre-treated the cells with QUE and exposed them to AFB1. The protective role of QUE was evaluated by measuring cytotoxicity, transcriptional changes (RNA-sequencing), lipid peroxidation (malondialdehyde production), and targeted post-transcriptional modifications (NQO1 and CYP3A enzymatic activity). The results demonstrated that QUE, like curcumin and resveratrol, reduced AFB1-induced cytotoxicity and lipid peroxidation and caused larger transcriptional variations than AFB1 alone. Most of the differentially expressed genes were involved in lipid homeostasis, inflammatory and immune processes, and carcinogenesis. As for enzymatic activities, QUE significantly reverted CYP3A variations induced by AFB1, but not those of NQO1. This study provides new knowledge about key molecular mechanisms involved in QUE-mediated protection against AFB1 toxicity and encourages in vivo studies to assess QUE’s bioavailability and beneficial effects on aflatoxicosis.

Detoxification of Aflatoxin B1 by Phytochemicals in Agriculture and Food Science

“…Differentially expressed gene analysis showed that quercetin treatment affected lipid homeostasis, inflammation, immune processes, and carcinogenesis. 80 Quercetin was also found to inhibit AFB 1 -induced cytotoxicity in bovine mammary epithelial cells by upregulating expression of GSTA1 which mediated the GSH conjugation of the AFBO. 65 AFB 1 can bind to human serum albumin (HSA), which is detrimental to the metabolism of AFB 1 and reduce the elimination rate of AFB 1 .…”

“…In addition, quercetin directly affected AFB 1 metabolism by inhibiting the phase I enzyme activity in bovine fetal hepatocyte-derived cells, thereby inhibiting AFB 1 -mediated cytotoxicity and lipid peroxidation. Differentially expressed gene analysis showed that quercetin treatment affected lipid homeostasis, inflammation, immune processes, and carcinogenesis . Quercetin was also found to inhibit AFB 1 -induced cytotoxicity in bovine mammary epithelial cells by up-regulating expression of GSTA1 which mediated the GSH conjugation of the AFBO .…”

Current Knowledge of Individual and Combined Toxicities of Aflatoxin B1 and Fumonisin B1 In Vitro

“…siamensis could inhibit DNA adduct formation and reduce metabolic activation of AFB1 to mitigate AFB1 toxicity in hepatoma cells [108,110]. Besides, quercetin could reduce AFB1-induced lipid peroxidation and reverted cytochromes P450 variations to show its mitigation capability in the liver [111]. Recently, Elbasuni et al also proved that Chlorella vulgaris could mitigate hepatic aflatoxicosis [111].…”

“…Besides, quercetin could reduce AFB1-induced lipid peroxidation and reverted cytochromes P450 variations to show its mitigation capability in the liver [111]. Recently, Elbasuni et al also proved that Chlorella vulgaris could mitigate hepatic aflatoxicosis [111]. They found that Chlorella vulgaris mitigated AFB1-induced oxidative stress and inflammatory condition after three week treatment [112] On other hand, curcumin and silymarin have been studied to have the capability to provide cytoprotection against toxicity induced by FB1 and specially to reduce ROS formation after 48h treatment in porcine kidney-15 cells [113].…”