Interactions of Mycotoxin Alternariol with Cytochrome P450 Enzymes and OATP Transporters

Fliszár-Nyúl, Eszter; Ungvári, Orsolya; Dombi, Ágnes; Özvegy‐Laczka, Csilla; Poór, Miklós

doi:10.3390/metabo13010045

Cited by 6 publications

(3 citation statements)

References 41 publications

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“…AOH have been reported to enhance the expression of CYP1A cytochrome in human cells of different tissue origin, especially in esophageal cells [ 44 , 45 ]. Another recent in vitro study has shown that AOH is a potent inhibitor of CYP1A2, CYP2C9, but not of CYP2C19, 2D6, and 3A4 [ 46 ]. The computational model predicted that AOH had high probability to be substrate for Cyp1A1, Cyp1A2 but also for Cyp2C12, Cyp1A6, Cyp2B6, Cyp2C, and Cyp2C9 ( Figure 3 ).…”

Section: Discussionmentioning

confidence: 99%

Using In Silico Approach for Metabolomic and Toxicity Prediction of Alternariol

Marin

Ţăranu

2023

Toxins

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Alternariol is a metabolite produced by Alternaria fungus that can contaminate a variety of food and feed materials. The objective of the present paper was to provide a prediction of Phase I and II metabolites of alternariol and a detailed ADME/Tox profile for alternariol and its metabolites using an in silico working model based on the MetaTox, SwissADME, pKCMS, and PASS online computational programs. A number of 12 metabolites were identified as corresponding to the metabolomic profile of alternariol. ADME profile for AOH and predicted metabolites indicated a moderate or high intestinal absorption probability but a low probability to penetrate the blood–brain barrier. In addition to cytotoxic, mutagenic, carcinogenic, and endocrine disruptor effects, the computational model has predicted other toxicological endpoints for the analyzed compounds, such as vascular toxicity, haemato-toxicity, diarrhea, and nephrotoxicity. AOH and its metabolites have been predicted to act as a substrate for different isoforms of phase I and II drug-metabolizing enzymes and to interact with the response to oxidative stress. In conclusion, in silico methods can represent a viable alternative to in vitro and in vivo tests for the prediction of mycotoxins metabolism and toxicity.

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Section: Discussionmentioning

confidence: 99%

Using In Silico Approach for Metabolomic and Toxicity Prediction of Alternariol

Marin

Ţăranu

2023

Toxins

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“…A rapid and highly sensitive method was validated for the quantification of probe substrates in dog liver microsomes (DLMs) following the guidelines for bioanalytical method validation [37]. The acetonitrile protein precipitation method was applied to develop a sensitive UPLC-MS/MS method for determining the specific metabolites of each CYP450 probe substrate [38][39][40][41]. As shown in Figure 1, there were no interfering peaks detected in the blank sample at the retention time of the target compounds and internal standard.…”

Section: Methods Validationmentioning

confidence: 99%

Inhibitory Mechanisms of Lekethromycin in Dog Liver Cytochrome P450 Enzymes Based on UPLC-MS/MS Cocktail Method

Sun,

Cao,

Qiu

et al. 2023

Molecules

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Lekethromycin (LKMS) is a synthetic macrolide compound derivative intended for use as a veterinary medicine. Since there have been no in vitro studies evaluating its potential for drug–drug interactions related to cytochrome P450 (CYP450) enzymes, the effect of the inhibitory mechanisms of LKMS on CYP450 enzymes is still unclear. Thus, this study aimed to evaluate the inhibitory effects of LKMS on dog CYP450 enzymes. A cocktail approach using ultra-performance liquid chromatography–tandem mass spectrometry was conducted to investigate the inhibitory effect of LKMS on canine CYP450 enzymes. Typical probe substrates of phenacetin, coumarin, bupropion, tolbutamide, dextromethorphan, chlorzoxazone, and testosterone were used for CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4, respectively. This study showed that LKMS might not be a time-dependent inhibitor. LKMS inhibited CYP2A6, CYP2B6, and CYP2D6 via mixed inhibition. LKMS exhibited mixed-type inhibition against the activity of CYP2A6 with an inhibition constant (Ki) value of 135.6 μΜ. LKMS inhibited CYP2B6 in a mixed way, with Ki values of 59.44 μM. A phenotyping study based on an inhibition assay indicated that CYP2D6 contributes to the biotransformation of LKMS. A mixed inhibition of CYP2D6 with Ki values of 64.87 μM was also observed. Given that this study was performed in vitro, further in vivo studies should be conducted to identify the interaction between LKMS and canine CYP450 enzymes to provide data support for the clinical application of LKMS and the avoidance of adverse interactions between other drugs.

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“…Examples of waste near to generation: aa felled tree; bfallen leaves But if the waste will not be utilised as soon as possible, it will be a culture medium for different microbes, fungi and moulds. The last ones produce carcinogenic, teratogenic, immunotoxic mycotoxins such as ochratoxin A [10], aflatoxins [10], deoxynivalenol [11], fumonisin [12]. In natural conditions, such mediums are distributed, which cause low concentration of pathogens.…”

Section: Biowaste Managementmentioning

confidence: 99%

Agrocenoses air improvement for longer and healthier people life

Ткаченко

Mileikovskyi

Satin

et al. 2023

22nd International Scientific Conference Engineering for Rural Development Proceedings

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In 2019, 99% of people in the world lived in areas violating WHO’s recommended air quality indicators. By WHO’s estimation, in 2019, air pollution caused 4.2 million premature deaths worldwide. The most harmful are PM2.5 particles, which penetrate the blood through the aerogematic barrier causing cardiovascular and respiratory diseases and cancer. PM10 can pass deeply into the lungs, but they are not so harmful. People always believed that rural air is healthy. Research at the University of Minnesota showed that 18 000 Americans die every year due to air pollution by agriculture, primarily, ammonia (NH3) from the decomposition of fertilizers and livestock waste (12.4 thousand deaths), and PM2.5 particles (4.8 thousand deaths). In polluted areas, plants have more aggressive allergenic pollen. Agricultural waste management and optimization of landscapes are effective ways of solving the problem. In this work, solutions are proposed to improve the air safety of agrocenoses. Minimization of contact of waste with air and its utilisation as soon as possible allows for avoiding decomposition. Converting to gasification boilers/ovens avoids releasing PM2.5 by heating. In addition, plants capable of purifying the air from relevant pollutants should be introduced in agrocenoses. The places for planting are forest protection strips, free places near roads, residential and administrative buildings, etc. In particular, the use of hedges with such plants can provide a local oasis of clean air around houses. In the case of dense land use and lack of free space, it is possible to introduce “green structures” on buildings. An assortment of plants for different regions of Ukraine is offered.

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Interactions of Mycotoxin Alternariol with Cytochrome P450 Enzymes and OATP Transporters

Cited by 6 publications

References 41 publications

Using In Silico Approach for Metabolomic and Toxicity Prediction of Alternariol

Using In Silico Approach for Metabolomic and Toxicity Prediction of Alternariol

Inhibitory Mechanisms of Lekethromycin in Dog Liver Cytochrome P450 Enzymes Based on UPLC-MS/MS Cocktail Method

Agrocenoses air improvement for longer and healthier people life

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