Biochemical interactions of dietary food contaminants with cytochrome P450 2E1: an in silico approach

Abstract

Aim: Food contaminants such as acrylamide, 3-monochloropropane-1,2-diol (3-MCPD), glycidyl stearate, deoxynivalenol, hydroxymethylfurfural, and zearalenone represent significant toxicological concerns in humans due to their potential genotoxic, hepatotoxic, and carcinogenic properties. This study aimed to investigate the molecular interactions of these contaminants with cytochrome P450 2E1 (CYP2E1), a key enzyme in xenobiotic metabolism, using an in silico approach. Methods: Molecular docking simulations were performed to assess the binding affinities and interaction profiles of selected food contaminants with the active site of human CYP2E1. The docking scores and binding poses were analyzed to predict possible metabolic outcomes and risks associated with exposure. Results: Docking analysis revealed variable binding affinities among the tested contaminants. Glycidyl stearate, zearalenone, and deoxynivalenol demonstrated stronger binding interactions (higher docking scores) compared to acrylamide and 3-MCPD, suggesting higher potential for CYP2E1-mediated metabolism. Quantitative results have been added: glycidyl stearate, deoxynivalenol, and zearalenone showed the stronger binding energies (−6.4, −7.2, and –7.9 kcal/mol), while acrylamide and 3-MCPD were weaker (−3.7 and −4.1 kcal/mol). Hydroxymethylfurfural showed an intermediate binding affinity (ΔG=–5.3 kcal/mol), suggesting a moderate potential for CYP2E1-mediated metabolism. Differential binding patterns highlighted possible metabolic activation or detoxification pathways. Conclusions: The results indicate that CYP2E1 plays an important role in mediating the biochemical responses to multiple food contaminants. Stronger interactions with certain contaminants suggest a higher risk of metabolic activation, which may contribute to their toxic effects. This study demonstrates the utility of molecular docking for predicting human biochemical responses and supports its use as a complementary tool in food safety risk assessment.

Keywords

food contaminants / cytochrome P450 2E1 (CYP2E1) / molecular docking / toxicology

References

[1] Lebelo K, Malebo N, Mochane MJ, Masinde M. Chemical Contamination Pathways and the Food Safety Implications along the Various Stages of Food Production: A Review. Int J Environ Res Public Health. 2021;18:5795.

[2] Li C, Li C, Yu H, Cheng Y, Xie Y, Yao W, et al. Chemical food contaminants during food processing: sources and control. Crit Rev Food Sci Nutr. 2021;61:1545—55.

[3] da Costa DS, Albuquerque TG, Costa HS, Bragotto APA. Thermal Contaminants in Coffee Induced by Roasting: A Review. Int J Environ Res Public Health. 2023;20:5586.

[4] Zahir A, Khan IA, Nasim M, Azizi MN, Azi F. Food process contaminants: formation, occurrence, risk assessment and mitigation strategies—a review. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2024;41:1242-74.

[5] Stadler RH, Theurillat V. Chemical Contaminants and Residues in Food. In: Schrenk D, Cartus A, editors. Heat—Generated Toxicants in Foods (Acrylamide, MCPD Esters, Glycidyl Esters, Furan, and Related Compounds). 2nd ed. Woodhead Publishing; 2017. pp. 171-95.

[6] Maher A, Nowak A. Chemical Contamination in Bread from Food Processing and Its Environmental Origin. Molecules. 2022;27:5406.

[7] Goh KM, Wong YH, Tan CP, Nyam KL. A summary of 2—, 3—MCPD esters and glycidyl ester occurrence during frying and baking processes. Curr Res Food Sci. 2021;4:460-9.

[8] Cheng W, Liu G, Wang L, Liu Z. Glycidyl Fatty Acid Esters in Refined Edible Oils: A Review on Formation, Occurrence, Analysis, and Elimination Methods. Compr Rev Food Sci Food Saf. 2017;16:263-81.

[9] Bryła M, Waśkiewicz A, Ksieniewicz—Woźniak E, Szymczyk K, Jędrzejczak R. ModifiedFusarium Mycotoxins in Cereals and Their Products—Metabolism, Occurrence, and Toxicity: An Updated Review . Molecules. 2018;23:963.

[10] Kamle M, Mahato DK, Gupta A, Pandhi S, Sharma B, Dhawan K, et al. Deoxynivalenol: An Overview on Occurrence, Chemistry, Biosynthesis, Health Effects and Its Detection, Management, and Control Strategies in Food and Feed. Microbiol Res. 2022;13:292-314.

[11] Rai A, Das M, Tripathi A. Occurrence and toxicity of a fusarium mycotoxin, zearalenone. Crit Rev Food Sci Nutr. 2020;60:2710-29.

[12] Kinkade CW, Rivera—Núñez Z, Gorcyzca L, Aleksunes LM, Barrett ES. Impact of Fusarium—Derived Mycoestrogens on Female Reproduction: A Systematic Review. Toxins (Basel). 2021;13:373.

[13] Chen J, Jiang S, Wang J, Renukuntla J, Sirimulla S, Chen J. A comprehensive review of cytochrome P450 2E1 for xenobiotic metabolism. Drug Metab Rev. 2019;51:178-95.

[14] Kessova I, Cederbaum AI. CYP2E1: biochemistry, toxicology, regulation and function in ethanol—induced liver injury. Curr Mol Med. 2003;3:509—18.

[15] Bhattacharyya S, Sinha K, Sil PC. Cytochrome P450s: mechanisms and biological implications in drug metabolism and its interaction with oxidative stress. Curr Drug Metab. 2014;15:719—42.

[16] Sugeçti S. İndoksakarb ve Abamektin İnsektisitlerinin Apis mellifera Üzerindeki Toksik Etkilerinin Moleküler Kenetlenme Yöntemi ile İncelenmesi. Gazi Üniversitesi Fen Fakültesi Dergisi. 2025;6:131-8.

[17] Cen C, Yu X, Shentu X, Miao S, Wang Y. Application of protein modeling and molecular simulation techniques in the field of food microbial contamination: principles, research status and future prospects. Crit Rev Food Sci Nutr. 2026;66:129-44.

[18] Sugeçti S. Effects of quercetin and sabinene on antioxidant and detoxification enzymes of model pest Drosophila melanogaster (Diptera: Drosophilidae): Molecular docking investigation. Süleyman Demirel Üniversitesi Fen Bilimleri Enstitüsü Dergisi. 2025;29:21-34.

[19] Chen Y, Zhang J, Lu J, Shi H, Lan P, Wang W, et al. Computational simulations uncover enantioselective metabolism of chiral triazole fungicides by human CYP450 enzymes: A case study of tebuconazole. Ecotoxicol Environ Saf. 2024;284:116865.

[20] Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, et al. PubChem 2025 update. Nucleic Acids Res. 2025;53:D1516-25.

[21] Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, et al. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem. 2009;30:2785—91.

[22] Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31:455-61.

[23] Garvey M. Food pollution: a comprehensive review of chemical and biological sources of food contamination and impact on human health. Nutrire. 2019;44:1.

[24] Stadler RH. Chemical Contaminants and Residues in Food. In: Schrenk D, editor. Heat—generated toxicants in foods: acrylamide, MCPD esters and furan. Woodhead Publishing; 2012. pp. 201-32.

[25] Frenzel F, Buhrke T, Wenzel I, Andrack J, Hielscher J, Lampen A. Use of in silico models for prioritization of heat—induced food contaminants in mutagenicity and carcinogenicity testing. Arch Toxicol. 2017;91:3157-74.

[26] Liang Y, Jiang Q, Gong Y, Yu Y, Zou H, Zhao J, et al. In vitro and in silico assessment of endocrine disrupting effects of food contaminants through pregnane X receptor. Food Chem Toxicol. 2023;175:113711.

[27] Dellafiora L, Dall’Asta C, Galaverna G. Toxicodynamics of Mycotoxins in the Framework of Food Risk Assessment—An In Silico Perspective. Toxins (Basel). 2018;10:52.

[28] Sugeçti S, Büyükgüzel E, Büyükgüzel K. Pathophysiologic Role of Intestinal Microbiota on Neurodegenerative Diseases. J Immunol Clin Microbiol. 2019;4:152-7.

[29] Sinyani A, Idowu K, Shunmugam L, Kumalo HM, Khan R. A molecular dynamics perspective into estrogen receptor inhibition by selective flavonoids as alternative therapeutic options. J Biomol Struct Dyn. 2023;41:4093—105.