Effect of UV irradiation on aflatoxin reduction: a cytotoxicity evaluation study using human hepatoma cell line

Patras, Ankit; Julakanti, Sharath; Yannam, Sudheer Kumar; Bansode, Rishipal R.; Burns, Mallory

doi:10.1007/s12550-017-0291-0

Cited by 40 publications

(42 citation statements)

References 29 publications

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“…21 As described above, analyte separation was achieved using a Kinetex C18 or EVO C18 octadecylsilane column (2.6 μ m, 50 × 2.1 mm, 100 Å) (Phenomenex) with a flow rate of 0.3 mL/min and column oven temperature 32 °C. The following LC gradient program was used: 5% B (0–1.0 min), linear gradient from 5 to 95% B (1.0–2.0 min), 95% B (2.0–3.0 min), 95 to 5% B (3.0–3.5 min), and returned to 5% B (3.5–5.0 min) until the end of the run (all v/v).…”

Section: Methodsmentioning

confidence: 99%

Cytochromes P450 1A2 and 3A4 Catalyze the Metabolic Activation of Sunitinib

Amaya

Durandis

Bourgeois

et al. 2018

Chem. Res. Toxicol.

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Sunitinib is a multitargeted tyrosine kinase inhibitor associated with idiosyncratic hepatotoxicity. The mechanisms of this toxicity are unknown. We hypothesized that sunitinib undergoes metabolic activation to form chemically reactive, potentially toxic metabolites which may contribute to development of sunitinib-induced hepatotoxicity. The purpose of this study was to define the role of cytochrome P450 (P450) enzymes in sunitinib bioactivation. Metabolic incubations were performed using individual recombinant P450s, human liver microsomal fractions, and P450-selective chemical inhibitors. Glutathione (GSH) and dansylated GSH were used as trapping agents to detect reactive metabolite formation. Sunitinib metabolites were analyzed by liquid chromatography–tandem mass spectrometry. A putative quinoneimine–GSH conjugate (M5) of sunitinib was detected from trapping studies with GSH and dansyl–GSH in human liver microsomal incubations, and M5 was formed in an NADPH-dependent manner. Recombinant P450 1A2 generated the highest levels of defluorinated sunitinib (M3) and M5, with less formation by P450 3A4 and 2D6. P450 3A4 was the major enzyme forming the primary active metabolite N-desethylsunitinib (M1). In human liver microsomal incubations, P450 3A inhibitor ketoconazole reduced formation of M1 by 88%, while P450 1A2 inhibitor furafylline decreased generation of M5 by 62% compared to control levels. P450 2D6 and P450 3A inhibition also decreased M5 by 54 and 52%, respectively, compared to control. In kinetic assays, recombinant P450 1A2 showed greater efficiency for generation of M3 and M5 compared to that of P450 3A4 and 2D6. Moreover, M5 formation was 2.7-fold more efficient in human liver microsomal preparations from an individual donor with high P450 1A2 activity compared to a donor with low P450 1A2 activity. Collectively, these data suggest that P450 1A2 and 3A4 contribute to oxidative defluorination of sunitinib to generate a reactive, potentially toxic quinoneimine. Factors that alter P450 1A2 and 3A activity may affect patient risk for sunitinib toxicity.

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Section: Methodsmentioning

confidence: 99%

Cytochromes P450 1A2 and 3A4 Catalyze the Metabolic Activation of Sunitinib

Amaya

Durandis

Bourgeois

et al. 2018

Chem. Res. Toxicol.

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“…Cell cytotoxicity analysis was carried out using the method described by Patras et al 16 with slight modification. The HepG2 cells (American Type Culture Collection (ATCC); HB-8065) with a cell plating density of 2 × 10 5 cells per well were seeded in a 12-well plate containing 10% (v/v) fetal bovine serum (FBS) in Eagle's minimal essential medium (EMEM).…”

Section: Cell Cytotoxicity Analysismentioning

confidence: 99%

“…UV irradiation has been demonstrated in literature as an effective physical method to inactivate chemical contaminants, and micro-organisms through photolysis and DNA damage, respectively [16][17][18][19][20] . This non-thermal technology is efficient in degrading aflatoxins because of their photosensitivity 21 .…”

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confidence: 99%

“…Dominant sources of UV treatment such as low pressure and medium pressure mercury lamps were used to degrade aflatoxins. In a study, 98% reduction of AFB 1 in water was observed at an UV dose of 4,880 mJ/cm 2 using a medium pressure UV lamp which emits irradiation between 200 and 360 nm wavelength 16 . Similarly, 100% reduction of AFB 1 in peanut oil was observed when UV intensity (220-400 nm) of 800 mJ/cm 2 was used for 30 min 22 .…”

mentioning

confidence: 99%

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Performance of a UV-A LED system for degradation of aflatoxins B1 and M1 in pure water: kinetics and cytotoxicity study

Stanley

Patras

Pendyala

et al. 2020

Sci Rep

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The efficacy of a UV-A light emitting diode system (LED) to reduce the concentrations of aflatoxin B 1 , aflatoxin M 1 (AFB 1 , AfM 1) in pure water was studied. This work investigates and reveals the kinetics and main mechanism(s) responsible for the destruction of aflatoxins in pure water and assesses the cytotoxicity in liver hepatocellular cells. Irradiation experiments were conducted using an LED system operating at 365 nm (monochromatic wavelength). Known concentrations of aflatoxins were spiked in water and irradiated at UV-A doses ranging from 0 to 1,200 mJ/cm 2. The concentration of AFB 1 and AfM 1 was determined by HPLC with fluorescence detection. LC-MS/MS product ion scans were used to identify and semi-quantify degraded products of AFB 1 and AfM 1. It was observed that UV-A irradiation significantly reduced aflatoxins in pure water. In comparison to control, at dose of 1,200 mJ/cm 2 UV-A irradiation reduced AFB 1 and AfM 1 concentrations by 70 ± 0.27 and 84 ± 1.95%, respectively. We hypothesize that the formation of reactive species initiated by UV-A light may have caused photolysis of AFB 1 and AfM 1 molecules in water. In cell culture studies, our results demonstrated that the increase of UV-A dosage decreased the aflatoxins-induced cytotoxicity in HepG2 cells, and no significant aflatoxin-induced cytotoxicity was observed at UV-A dose of 1,200 mJ/cm 2. Further results from this study will be used to compare aflatoxins detoxification kinetics and mechanisms involved in liquid foods such as milk and vegetable oils. Filamentous fungi invading various feed crops produces toxic secondary metabolites called mycotoxins which possess a serious threat to consumer health 1. Aflatoxins are highly cytotoxic and carcinogenic secondary metabolites, produced predominantly by Aspergillus flavus and Aspergillus paraciticus, especially in the tropical and subtropical regions as hot and humid climatic conditions are optimal for mold growth and toxin production 2,3. Aflatoxins are difuranocoumarin derivatives formed from the polyketide pathway and include a group of 17 aflatoxins, among which AFB 1 is the predominant and is highly toxic 4. Aflatoxin contamination in animal feed results in their carry-over in foods of animal origin such as eggs and milk. The major AFB 1 metabolite in milk, AFM 1, is formed due to the action of hepatic cytochrome P450-dependent polysubstrate monoxygenase enzyme superfamily as a result of the hydroxylation of the fourth carbon of the terminal furan ring. In dairy cows, the biotransformation rate of AFB 1 to AFM 1 ranges from 0.3 to 6.2% 5,6. Aflatoxins are detrimental upon ingestion, inhalation, and skin contact; and the consequences of aflatoxin infection are collectively called aflatoxicosis. The biotransformation of AFB 1 in liver results in the production of AFB 1-8,9-epoxide which is highly related to the incidence of hepatocellular carcinoma 6,7. The carcinogenicity of AFM 1 is approximately one-tenth of that of AFB 1 The International Agency for Research on Cancer in 1993 classif...

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“…Several radiation sources have been evaluated thus far and many of them were found to be effective. For example, the advantageous effects of UV in liquid phase (Patras et al, 2017), gamma irradiation in corn (Markov et al, 2015;Serra et al, 2018), in other cereal kernels (Mohamed et al, 2015), in peanuts (Patil et al, 2019) and in poultry feed (Herzallah et al, 2008) have been reported in a number of publications. Direct sunlight was also effective in aflatoxin reduction in poultry feed (Herzallah et al, 2008) and, in addition to exposures to direct light, the applicability of pulsed light has also been tested and evaluated, and it has already been employed in new decontamination technologies (Moreau et al, 2013).…”

Section: Shi Et Al 2017mentioning

confidence: 99%