Cellular interactions and metabolism of aflatoxin: An update

McLean, Michelle; Dutton, Michael F.

doi:10.1016/0163-7258(94)00054-7

Cited by 222 publications

(146 citation statements)

References 148 publications

Supporting

Mentioning

123

Contrasting

Unclassified

Order By: Relevance

“…In HepG2 cells, co-exposure to OTA significantly decreased DNA damage induced by AFB1, not only in breaks and apurinic sites but also in FPG-sensitive sites (Corcuera et al 2011a). AFB1 is bioactivated in liver by cytochrome P450 and its epoxide metabolite attacks DNA forming adducts (McLean and Dutton, 1995). The primary lesion evolves to secondary injuries such as apurinic sites (AP) that would be detected as direct strand breaks by the comet assay; or imidazole AFB1 formamidopyrimidine opened rings (AFB1-FAPY) (Bedard and Massey, 2006), that could be detected by incubating the DNA with a formamidopyrimidine glycosylase enzyme such as FPG.…”

Section: Discussionmentioning

confidence: 99%

“…It may also cause tumors in other organs, such as colon and kidney (EFSA, 2007). It is bioactivated in liver by cytochrome P450 and its epoxide metabolite attacks DNA forming adducts (McLean and Dutton, 1995). AFB1 is a clastogen that has been tested extensively for genotoxicity in vivo and in vitro, giving consistently positive results (IARC, 1987).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genotoxicity of Aflatoxin B1 and Ochratoxin A after simultaneous application of the in vivo micronucleus and comet assay

Corcuera

Vettorazzi

Arbillaga

et al. 2015

Food and Chemical Toxicology

View full text Add to dashboard Cite

(max. 200 words)Aflatoxin B1 (AFB1) and Ochratoxin A (OTA) are genotoxic mycotoxins that can contaminate a variety of foodstuffs, the liver and the kidney being their target organ, respectively. The micronucleus (MN) assay (bone marrow) and the comet assay (liver and kidney) were performed simultaneously in F344 rats, treated with AFB1 (0.25 mg/kg b.w.), OTA (0.5 mg/kg b.w.) or both mycotoxins. After AFB1 treatment, histopathology and biochemistry analysis showed liver necrosis, focal inflammation and an increase in Alanine Aminotransferase and Aspartate Aminotransferase. OTA alone did not cause any alteration. The acute hepatotoxic effects caused by AFB1 were less pronounced in animals treated with both mycotoxins. With regard to the MN assay, after 24h, positive results were obtained for AFB1 and negative results were obtained for OTA, although both toxins caused bone marrow toxicity. In the combined treatment, OTA reduced the toxicity and the number of MN produced by AFB1. In the comet assay, after 3h, positive results were obtained for AFB1 in the liver and for OTA in the 1 kidney. The combined treatment reduced DNA damage in the liver and had no influence in the kidney. Altogether, these results may be indicative of an antagonistic relationship regarding the genotoxicity of both mycotoxins.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genotoxicity of Aflatoxin B1 and Ochratoxin A after simultaneous application of the in vivo micronucleus and comet assay

Corcuera

Vettorazzi

Arbillaga

et al. 2015

Food and Chemical Toxicology

View full text Add to dashboard Cite

show abstract

“…The liver is the main target organ for aflatoxins and chronic exposure to low levels in foodstuffs causes liver fibrosis and primary liver cancer [8] but, AFB 1 may also cause tumors in other organs, such as colon and kidney [9]. It is bioactivated in liver by cytochrome P450 and its epoxide metabolite attacks DNA forming adducts [10] that might evolve to secondary injuries such as apurinic sites (AP) or imidazole AFB 1 formamidopyrimidine opened rings (AFB 1 -FAPY) [11]. The metabolite AFB 1 -FAPY induces G-T transversion, and is a good indicator of AFB 1 exposure in urine [12].…”

Section: Introductionmentioning

confidence: 99%

Low level of Ochratoxin A enhances Aflatoxin B1 Induced Cytotoxicity and Lipid Peroxydation in Both Human Intestinal (Caco-2) and Hepatoma (HepG2) Cells Lines

Halbin¹,

Brou²,

Dago³

2013

IJNFS

View full text Add to dashboard Cite

Abstract:Aflatoxin B 1 (AFB 1 ) and ochratoxin A (OTA) are contaminants which co-occurred in the same food such as cereals. The few studies performed on their interactive effect had revealed additive or antagonistic cytotoxic effect according to cells endpoints and concentrations of both mycotoxins. The aim of the present study was to investigate in a possible influence of very low level of ochratoxin A in aflatoxin B 1 toxic action regarding cellular endpoints such as malonedialdehyde (MDA) production and cells viability as evaluated by lysosome and mitochondria integrities and cell lactate dehydrogenase (LDH) leakage. OTA (20nM) and AFB 1 were tested in combination in both human intestinal (Caco-2) and hepatoma (HepG2) cells lines. As results, OTA alone tested at 20nM was not cytotoxic and did not induce MDA production in both Caco-2 and HepG2 cells line. Interestingly, combined to AFB 1 (10µM), OTA enhanced markedly AFB 1 cytotoxic effect. OTA significantly increased cell lysosomes damage induced by AFB 1 from 24% to 38% (+14%) and from 28% to 43% (+15%) respectively in Caco-2 and HepG2 cells line (p<0.05). Similarly, OTA enhanced inhibition of mitochondria succinate dehydrogenase activity induced by AFB 1 until to +15% and +6% respectively in Caco-2 and HepG2 cells line (p<0.05). On cell necrosis marker, the mixture of OTA and AFB 1 induced more LDH leakage when compared to AFB 1 alone with increase of +14% and +12% respectively in Caco-2 and HepG2 cells line (p<0.05). Finally, on MDA production, AFB 1 + OTA induced more intensively MDA production when compared to AFB 1 alone with +49% and +110% of increasing in both Caco-2 and HepG2 cells line (p<0.01). Taken together, our results suggested that combined AFB 1 and OTA induced all the toxicities observed with the mycotoxins separately but more intensively suggesting synergistic or potentiating effect. Moreover, AFB 1 or its association with OTA had been found very potent in human hepatic cells HepG2 in necrosis induction but especially in lipids oxidative damage confirming oxidative stress as one of keys pathways in toxic action of AFB 1 .

show abstract

“…The IARC classified Aflatoxin B1 (AFB1) and OTA as class 1 (human carcinogen) and class 2B (possible human carcinogen), respectively [3,4,5]. Aflatoxin B1 is genotoxic in vivo and in vitro; its target organ is liver but it may cause tumors in other organs such as colon and kidney [6,7].…”

Section: Introductionmentioning

confidence: 99%

Validation of a UHPLC-FLD analytical method for the simultaneous quantification of aflatoxin B1 and ochratoxin a in rat plasma, liver and kidney

Corcuera

Ibáñez-Vea

Vettorazzi

et al. 2011

Journal of Chromatography B

View full text Add to dashboard Cite

addresses of all coauthors: Laura-Ana Corcuera: lcorcuer@alumni.unav.es, María Ibáñez-Vea: mivea@alumni.unav.es, Ariane Vettorazzi: avettora@alumni.unav.es, Adela López de Cerain: acerain@unav.es. 2 ABSTRACTA rapid and simple method for the simultaneous quantification of AFB1 and OTA in rat plasma, liver and kidney by UHPLC-FLD has been successfully validated according to the following criteria: selectivity, stability, linearity, precision, accuracy, recovery, robustness and limits of quantification and detection. The extraction method, calibration curves and chromatographic conditions are common for the three matrices. Plasma and homogenized tissue samples (100 µL) were extracted with acetonitrile-formic acid mixture (99:1) (300 µL). Chromatographic separation was performed with a mixture of water and acetonitrile:methanol (50:50), both acidified with 0.5% of formic acid using a gradient profile. The method avoids the use of immunoaffinity columns and allows reduction of sample and solvent volumes as well as toxic wastes. The detection is based on a photochemical reaction which enhances the AFB1 response without affecting the OTA signal before reaching the fluorescent detector. The mycotoxin recovery for each matrix was very efficient, between 93% and 96% for AFB1 and between 94% and 96% for OTA. For both mycotoxins the LOQs were 2 µg/L in plasma and 8 µg/kg in liver and kidney. The method has successfully been applied to rat samples after a single oral administration of a mixture of AFB1 and OTA and it could be a useful tool in toxicokinetic and toxicological studies.

show abstract

Cellular interactions and metabolism of aflatoxin: An update

Cited by 222 publications

References 148 publications

Genotoxicity of Aflatoxin B1 and Ochratoxin A after simultaneous application of the in vivo micronucleus and comet assay

Genotoxicity of Aflatoxin B1 and Ochratoxin A after simultaneous application of the in vivo micronucleus and comet assay

Low level of Ochratoxin A enhances Aflatoxin B1 Induced Cytotoxicity and Lipid Peroxydation in Both Human Intestinal (Caco-2) and Hepatoma (HepG2) Cells Lines

Validation of a UHPLC-FLD analytical method for the simultaneous quantification of aflatoxin B1 and ochratoxin a in rat plasma, liver and kidney

Contact Info

Product

Resources

About