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In Vivo Genotoxicity and Toxicity Assessment of Sterigmatocystin Individually and in Mixture with Aflatoxin B1
Maria Alonso-Jauregui1, Adela López de Cerain1, Amaya Azqueta1
1MITOX Research Group, Department of Pharmacology and Toxicology, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
Abstract:
Mycotoxins are natural food and feed contaminants produced by several molds. The primary mode of exposure in humans and animals is through mixtures. Aflatoxin B1 (AFB1) and sterigmatocystin (STER) are structurally related mycotoxins that share the same biosynthetic route. Few in vivo genotoxicity assays have been performed with STER. In the present genotoxicity study, Wistar rats were dosed orally with STER (20 mg/kg b.w.), AFB1 (0.25 mg/kg b.w.) or a mixture of both in an integrated micronucleus (bone marrow) and comet study (liver and kidney). STER was dosed at the highest feasible dose in corn oil. No increase in the percentage of micronuclei in bone marrow was observed at any condition. Slight DNA damage was detected in the livers of animals treated with AFB1 or the mixture (DNA strand breaks and Fpg (Formamidopyrimidine DNA glycosylase)-sensitive sites, respectively). Plasma, liver, and kidney samples were analyzed with LC-MS/MS demonstrating exposure to both mycotoxins. General toxicity parameters (organs absolute weight, biochemistry, and histopathology) were not altered either individually or in the mixture. The overall absence of individual genotoxicity did not allow us to set any type of interaction in the mixture. However, a possible toxicokinetic interaction was observed.
Insights
This study investigated the genotoxicity of sterigmatocystin (STER) and aflatoxin B1 (AFB1) in rats. While no genotoxicity was observed, a potential toxicokinetic interaction between these mycotoxins warrants further research.
Area of Science:
- Food Science
- Toxicology
- Genetics
Background:
- Mycotoxins, such as aflatoxin B1 (AFB1) and sterigmatocystin (STER), are common contaminants in food and feed.
- Exposure often occurs through mixtures, necessitating studies on their combined effects.
- Sterigmatocystin (STER) has limited in vivo genotoxicity data available.
Purpose of the Study:
- To evaluate the in vivo genotoxicity of STER, AFB1, and their mixture.
- To investigate potential interactions between STER and AFB1 at the genotoxic and toxicokinetic levels.
Main Methods:
- Wistar rats were orally dosed with STER, AFB1, or a mixture.
- An integrated micronucleus (bone marrow) and comet assay (liver and kidney) were performed.
- LC-MS/MS was used to confirm mycotoxin exposure; general toxicity was assessed.
Main Results:
- No significant increase in micronuclei was observed in bone marrow.
- Slight DNA damage (strand breaks and Fpg-sensitive sites) was detected in livers exposed to AFB1 or the mixture.
- No alterations in general toxicity parameters were found, but a possible toxicokinetic interaction was suggested.
Conclusions:
- Individual genotoxicity of STER and AFB1 was not confirmed under the tested conditions.
- The study did not establish genotoxic interactions in the mixture due to the absence of individual genotoxicity.
- A potential toxicokinetic interaction between STER and AFB1 warrants further investigation.
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