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High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents (HPHC)
Published on: May 10, 2016
Aflatoxin B1-induced toxicity in HepG2 cells inhibited by carotenoids: morphology, apoptosis and DNA damage
Lalini Reddy1, Bharti Odhav, Kanti Bhoola
1Department of Biotechnology, Durban Institute of Technology, Durban 4000, South Africa.
Abstract:
Aflatoxin B1 (AFB1) is a fungal toxin that has been associated with primary hepatocellular carcinoma (HCC) in humans. This study was undertaken to determine the cellular and molecular mechanisms by which the antioxidants beta-carotene and lycopene inhibit AFB1-induced toxic changes in human hepatocytes (HepG2 cells). An in vitro system was optimized to test the chemoprotective effects of lycopene and beta-carotene on HepG2 cells exposed to different concentrations of AFB1. Ultrastructurally, HepG2 cells cultured in the presence of AFB1 showed mitochondrial damage, nuclear condensation and a loss of cell-to-cell contact; the latter was reflected in the observation of dysfunctional gap junctions, resulting in a loss of cell-to-cell communication. At the genomic level, AFB1 formed AFB1-N7-guanine adducts, caused apoptotic cell death and suppressed p53 protein expression. In the presence of the carotenoids, survival of cells exposed to AFB1 was increased, and there was also a significant increase in cellular mitochondrial activity. Our results demonstrate that HepG2 cells pretreated with lycopene and beta-carotene are protected from the toxic effects of AFB1 at both the cellular and molecular levels.
Insights
Beta-carotene and lycopene protect human liver cells from aflatoxin B1 (AFB1) damage. These antioxidants prevent AFB1-induced cell death and preserve cell function, offering potential chemoprotective strategies against liver cancer.
Area of Science:
- Hepatology
- Toxicology
- Nutritional Biochemistry
Background:
- Aflatoxin B1 (AFB1) is a potent mycotoxin linked to hepatocellular carcinoma (HCC).
- Understanding the protective mechanisms of antioxidants against AFB1 toxicity is crucial for cancer prevention.
Purpose of the Study:
- To investigate the cellular and molecular mechanisms of beta-carotene and lycopene in inhibiting AFB1-induced toxicity in human hepatocytes.
- To evaluate the chemoprotective effects of these carotenoids against AFB1 exposure in vitro.
Main Methods:
- Optimized an in vitro system using human hepatocytes (HepG2 cells).
- Exposed cells to varying concentrations of AFB1 with and without beta-carotene and lycopene.
- Performed ultrastructural analysis and assessed genomic changes, including adduct formation, apoptosis, and p53 expression.
Main Results:
- AFB1 induced mitochondrial damage, nuclear condensation, and loss of cell-to-cell communication in HepG2 cells.
- AFB1 exposure led to AFB1-N7-guanine adducts, apoptosis, and suppressed p53 protein expression.
- Beta-carotene and lycopene pretreatment increased cell survival, enhanced mitochondrial activity, and protected against AFB1-induced cellular and molecular damage.
Conclusions:
- Beta-carotene and lycopene demonstrate significant chemoprotective effects against AFB1 toxicity in human hepatocytes.
- These antioxidants mitigate AFB1-induced cellular damage and molecular alterations, including DNA adduct formation and apoptosis.
- The findings support the potential role of beta-carotene and lycopene as dietary chemopreventive agents against AFB1-related liver damage.
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