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Mycotoxin contamination of feed poses a serious threat to the poultry industry, causing significant economic losses. Traditional adsorbents are ineffective against a wide range of toxins and can reduce the nutritional value of feed. Therefore, developing strategies to activate the animal's endogenous detoxification systems is a pressing issue. This study examined the efficacy of the complex phytogenic supplement (CPS) "Rezovet," containing N-acetylcysteine (NAC), alkylresorcinols, and indole compounds, under experimental mycotoxicosis induced by zearalenone (ZEN) and ochratoxin A (OA). An in vitro experiment on the human hepatoma cell line HepG2 demonstrated that "Rezovet" and its components reliably activate nuclear factor 2 (NRF2), the main regulator of the antioxidant and detoxification response. NRF2 activation was accompanied by an increase in glutathione-S-transferase (GST) gene mRNA expression and its total activity. Furthermore, NAC and indole-3-propionic acid induced a cytoprotective autophagic response in ZEN-exposed cells. Inhibition of autophagy by chloroquine eliminated the protective effect. In an in vivo experiment on Cobb-500 broilers (n=120), the addition of Rezovet (0.5 kg/t feed) to a diet contaminated with ZEN (0.5 mg/kg) and OA (0.25 mg/kg) significantly (p<0.05) reduced liver damage and oxidative stress (a 35% decrease in malondialdehyde levels, a 50% increase in glutathione), while simultaneously increasing GST activity by 40%. Significant improvements in productivity were recorded: livestock survival increased by 4.2%, live weight at 28 days increased by 8.5%, and feed conversion improved by 5.7% compared to the group receiving mycotoxins alone. Metagenomic analysis revealed a 152% increase in the proportion of the commensal bacterium Akkermansia muciniphila in the caecal microbiome and a suppression of urease-producing bacteria (Proteus spp., Klebsiella spp.) in the litter. The synergistic mechanism of action of Rezovet, combining the activation of cellular defense systems and the modulation of microbial communities through mechanisms described in the theory of microbial autoregulation, is discussed. Rezovet is shown to be an effective non-adsorptive agent for the biological detoxification of mycotoxins and microbiome management.
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26. Tieu S., Charchoglyan A., Paulsen L., Wagter-Lesperance L., Shandilya U., Bridle B., Mallard B., Karrow N. N-acetylcysteine and Its Immunomodulatory Properties in Humans and Domesticated Animals. Antioxidants. 2023. Vol. 12. No. 10. P. 1867.
27. Bischoff S.C., Barbara G., Buurman W., Ockhuizen T., Schulzke J.-D., Serino M., Tilg H., Watson A., Wells J. Intestinal permeability – a new target for disease prevention and therapy. BMC Gastroenterolo-gy. 2014. Vol. 14. P. 189.
28. Zelante T., Iannitti R., Cunha C., De Luca A., Giovannini G., Pieraccini G., Zecchi R., D'Angelo C., Massi-Benedetti C., Fallarino F., Carvalho A., Puccetti P., Romani L. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity. 2013. Vol. 39. No. 2. P. 372 – 385.
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30. Jackman J., Hakobyan A., Zakaryan H., Elrod C. Inhibition of African swine fever virus in liquid and feed by medium-chain fatty acids and glycerol monolaurate. Journal of Animal Science and Biotechnology. 2020. Volume 11. P. 114.
2. Gruber-Dorninger C., Jenkins T., Schatzmayr G. Global mycotoxin occurrence in feed: A ten-year sur-vey. Toxins. 2019. Vol. 11. No. 7. P. 375.
3. Zinedine A., Soriano J.M., Moltó J.C., Mañes J. Review on the toxicity, occurrence, metabolism, de-toxification, regulations and intake of zearalenone: an oestrogenic mycotoxin. Food and Chemical Toxi-cology. 2007. Vol. 45. No. 1. P. 1 – 18.
4. Kolosova A., Stroka J. Substances for reduction of the contamination of feed by mycotoxins: A review. World Mycotoxin Journal. 2011. Vol. 4. No. 3. P. 225 – 256.
5. Döll S., Dänicke S. The Fusarium toxins deoxynivalenol (DON) and zearalenone (ZON) in animal feeding. Preventive Veterinary Medicine. 2011. Vol. 102. No. 2. P. 132 – 145.
6. Li P., Su R., Lai D., Wang M., Liu Y., Zhou L. Detoxication of Mycotoxins through Biotransformation. Toxins. 2020. Vol. 12. No. 2. P. 121.
7. Ma Q. Role of nrf2 in oxidative stress and toxicity. Annual Review of Pharmacology and Toxicology. 2013. Vol. 53. P. 401 – 426.
8. He F., Ru X., Wen T. NRF2, a Transcription Factor for Stress Response and Beyond. International Journal of Molecular Sciences. 2020. Vol. 21. No. 13. P. 4777.
9. Lee R., Kim D.-W., Lee W.-Y., Park H.-J. Zearalenone Induces Apoptosis and Autophagy in a Spermatogonia Cell Line. Toxins. 2022. Vol. 14. No. 2. P. 148.
10. Guerre P. Mycotoxin and Gut Microbiota Interactions. Toxins. 2020. Vol. 12. No. 12. P. 769.
11. Dodson M., Chen W.-T., The untapped potential of targeting NRF2 in neurodegenerative disease. Frontiers in Aging. 2023. Vol. 4. P. 1270838.
12. Zabolotneva A., Shatova O., Sadova A., Shestopalov A., Roumiantsev S. An Overview of Alkylres-orcinols Biological Properties and Effects. Journal of Nutrition and Metabolism. 2022. Vol. 2022. P. 4667607.
13. Hayes J., Flanagan J., Jowsey I. Glutathione transferases. Annual Review of Pharmacology and Toxicology. 2005. Vol. 45. P. 51 – 88.
14. Van den Bogaard E., Esser C., Perdew G. The aryl hydrocarbon receptor at the forefront of host-microbe interactions in the skin: A perspective on current knowledge gaps and directions for future re-search and therapeutic applications. Experimental Dermatology. 2021. Vol. 30. No. 10. P. 1477 – 1483.
15. Awad W., Hess C., Hess M. Enteric pathogens and their toxin-induced disruption of the intestinal barrier through alteration of tight junctions in chickens. Toxins. 2017. Vol. 9. No. 2. P. 60.
16. Oni A., Oke O. Gut health modulation through phytogenics in poultry: mechanisms, benefits, and application. Frontiers in Veterinary Science. 2025. Vol. 12. P. 1216734.
17. Shimizu K. Metabolic Regulation of a Bacterial Cell System with Emphasis on Escherichia coli Metabolism. ISRN Biochemistry. 2013. Vol. 2013. P. 645983.
18. Nikolaev Y., Mulyukin A., Stepanenko I., El-Registan G. Autoregulation of the stress response in microorganisms. Microbiology. 2006. Vol. 75, No. 4. P. 420 – 426.
19. Suzina N., Mulyukin A., Dmitriev V., Nikolaev Y., Sorokina A., Bobkova Y., Barinova E., Plakunov V., El-Registan G.I., Duda V. The structural bases of long-term anabiosis in non-spore-forming bacteria. Advances in Space Research. 2006. Vol. 38. No. 6. P. 1209 – 1219.
20. Jian H., Liu Y., Wang X., Dong X., Zou X. Akkermansia muciniphila as Next-Generation Probiotic in Modulating Human Metabolic Homeostasis and Disease Progression: A Role Mediated by Gut-Liver-Brain Axes? International Journal of Molecular Sciences. 2023. Vol. 24. No. 4. P. 3900.
21. Yu M., Wang O., Ma Y., Li L., Yu K., Zhang Z., Chen G., Li X., Xiao W., Xu P., Yang H. Aryl Hydrocarbon Receptor Activation Modulates Intestinal Epithelial Barrier Function by Maintaining Tight Junction Integrity. International Journal of Biological Sciences. 2018. Vol. 14. No. 1. P. 69 – 77.
22. Obianwuna U., Chang X., Oleforuh-Okoleh V., Onu P., Zhang H., Qiu K., Wu S. Phytobiotics in poultry: revolutionizing broiler chicken nutrition with plant-derived gut health enhancers. Journal of Animal Science and Biotechnology. 2024. Vol. 15. P. 169.
23. Jiang X., Aro T. Ammonia Emission in Poultry Facilities: A Review for Tropical Climate Areas. At-mosphere. 2021. Vol. 12. No. 9. P. 1091.
24. Luis B., Domingues F., Duarte A.P. Biological properties of plant alkylresorcinols: a mini-review. Mini-Reviews in Medicinal Chemistry. 2016. Vol. 16. No. 11. P. 851 – 854.
25. Marchetti M., Zema L., Gazzaniga A. An Overview of Alkylresorcinols Biological Properties and Effects. Journal of Nutrition and Metabolism. 2022. Vol. 2022. P. 4667607.
26. Tieu S., Charchoglyan A., Paulsen L., Wagter-Lesperance L., Shandilya U., Bridle B., Mallard B., Karrow N. N-acetylcysteine and Its Immunomodulatory Properties in Humans and Domesticated Animals. Antioxidants. 2023. Vol. 12. No. 10. P. 1867.
27. Bischoff S.C., Barbara G., Buurman W., Ockhuizen T., Schulzke J.-D., Serino M., Tilg H., Watson A., Wells J. Intestinal permeability – a new target for disease prevention and therapy. BMC Gastroenterolo-gy. 2014. Vol. 14. P. 189.
28. Zelante T., Iannitti R., Cunha C., De Luca A., Giovannini G., Pieraccini G., Zecchi R., D'Angelo C., Massi-Benedetti C., Fallarino F., Carvalho A., Puccetti P., Romani L. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity. 2013. Vol. 39. No. 2. P. 372 – 385.
29. Lara L., Rostagno M. Impact of heat stress on poultry production. Animals. 2013. Vol. 3. No. 2. P. 356 – 369.
30. Jackman J., Hakobyan A., Zakaryan H., Elrod C. Inhibition of African swine fever virus in liquid and feed by medium-chain fatty acids and glycerol monolaurate. Journal of Animal Science and Biotechnology. 2020. Volume 11. P. 114.
Koluga E.V. Influence of the complex phytogenic additive "Resovet" on detoxification systems, antioxidant protection, productivity and intestinal microbiocenosis in broilers under mycotoxicosis conditions. Chemical Bulletin. 2025. 8 (4). 6. https://doi.org/10.58224/2619-0575-2025-8-4-6