actabiomedicaActa Biomedica ScientificaActa Biomedica Scientifica2541-94202587-9596Scientific Centre for Family Health and Human Reproduction Problems10.29413/ABS.2022-7.3.19actabiomedica-3565Research ArticleМОРФОЛОГИЯ, ФИЗИОЛОГИЯ И ПАТОФИЗИОЛОГИЯMORPHOLOGY, PHYSIOLOGY AND PATHOPHYSIOLOGYЭкспрессия генов у сельскохозяйственной птицы под влиянием Т-2 токсина и применения биопрепаратовGene expression in farm poultry under the influence of T-2 toxin and the use of biological preparationshttps://orcid.org/0000-0002-5846-5105ЙылдырымЕ. А.YildirimE. A.

 доктор биологических наук, главный биотехнолог молекулярно-генетической лаборатории; профессор кафедры крупного животноводства

196602, г. Санкт-Петербург, г. Пушкин, ул. Малиновская, 8, лит. А, пом. 7-Н, Россия 

196601, г. Санкт-Петербург, г. Пушкин, Петербургское шоссе, 2, Россия 

 Dr. Sc. (Biol.), Chief Biotechnologist at the Molecular Genetic Laboratory, ; Professor at the Department of Large Animal Husbandry

Malinovskaya str. 8, lit. A, Saint Petersburg, Pushkin 196602, Russian Federation

Petersburgskoye highway 2, Saint Petersburg, Pushkin 196601, Russian Federation 

deniz@biotrof.ruhttps://orcid.org/0000-0002-3088-0454ГрозинаА. А.GrozinaA. A.

 кандидат биологических наук, главный научный сотрудник, заведующая отделом физиологии и биохимии

141311, г. Сергиев Посад, ул. Птицеградская, 10, Россия

 Cand. Sc. (Biol.), Chief Research Officer, Head of the Department of Physiology and Biochemistry

 Ptitsegradskaya str. 10, Sergiev Posad 141311, Russian Federation 

alena_fisinina@mail.ruhttps://orcid.org/0000-0003-2789-4844ИльинаЛ. А.IlinaL. A.

 кандидат биологических наук, начальник молекулярно-генетической лаборатории; доцент кафедры крупного животноводства

196602, г. Санкт-Петербург, г. Пушкин, ул. Малиновская, 8, лит. А, пом. 7-Н, Россия

196601, г. Санкт-Петербург, г. Пушкин, Петербургское шоссе, 2, Россия 

 Cand. Sc. (Biol.), Head of the Molecular Genetic Laboratory; Associate Professor at the Department of Large Animal Husbandry

Malinovskaya str. 8, lit. A, Saint Petersburg, Pushkin 196602, Russian Federation

Petersburgskoye highway 2, Saint Petersburg, Pushkin 196601, Russian Federation 

ilina@biotrof.ruhttps://orcid.org/0000-0001-8789-9837ФилипповаВ. А.FilippovaV. A.

 биотехнолог молекулярно-генетической лаборатории; заведующий лабораторией кафедры крупного животноводства

196602, г. Санкт-Петербург, г. Пушкин, ул. Малиновская, 8, лит. А, пом. 7-Н, Россия

196601, г. Санкт-Петербург, г. Пушкин, Петербургское шоссе, 2, Россия 

Biotechnologist at the Molecular Genetic Laboratory; Head of the Laboratory of the Department of Large Animal Husbandry

Malinovskaya str. 8, lit. A, Saint Petersburg, Pushkin 196602, Russian Federation

Petersburgskoye highway 2, Saint Petersburg, Pushkin 196601, Russian Federation 

filippova@biotrof.ruhttps://orcid.org/0000-0002-8795-6659ЛаптевГ. Ю.LaptevG. Y.

 доктор биологических наук, директор; профессор кафедры крупного животноводства

196602, г. Санкт-Петербург, г. Пушкин, ул. Малиновская, 8, лит. А, пом. 7-Н, Россия

196601, г. Санкт-Петербург, г. Пушкин, Петербургское шоссе, 2, Россия 

 Dr. Sc. (Biol.), Head; Professor at the Department of Large Animal Husbandry

Malinovskaya str. 8, lit. A, Saint Petersburg, Pushkin 196602, Russian Federation

Petersburgskoye highway 2, Saint Petersburg, Pushkin 196601, Russian Federation 

laptev@biotrof.ruhttps://orcid.org/0000-0002-4336-8273ПономареваЕ. С.PonomarevaE. S.

 биотехнолог молекулярно-генетической лаборатории

196602, г. Санкт-Петербург, г. Пушкин, ул. Малиновская, 8, лит. А, пом. 7-Н, Россия

 Biotechnologist at the Molecular Genetic Laboratory

Malinovskaya str. 8, lit. A, Saint Petersburg, Pushkin 196602, Russian Federation

kate@biotrof.ruhttps://orcid.org/0000-0001-8424-4114ДубровинА. В.DubrowinA. V.

 кандидат ветеринарных наук, биотехнолог молекулярно-генетической лаборатории

196602, г. Санкт-Петербург, г. Пушкин, ул. Малиновская, 8, лит. А, пом. 7-Н, Россия

 Cand. Sc. (Vet.), Biotechnologist at the Molecular Genetic Laboratory

Malinovskaya str. 8, lit. A, Saint Petersburg, Pushkin 196602, Russian Federation

dubrovin@biotrof.ruhttps://orcid.org/0000-0002-9541-6839КалиткинаК. А.KalitkinaK. A.

 биотехнолог молекулярно-генетической лаборатории; студент кафедры крупного животноводства (направления «Зоотехния», магистерская программа «Селекция в частной зоотехнии»)

196602, г. Санкт-Петербург, г. Пушкин, ул. Малиновская, 8, лит. А, пом. 7-Н, Россия

196601, г. Санкт-Петербург, г. Пушкин, Петербургское шоссе, 2, Россия 

 Biotechnologist at the Molecular Genetic Laboratory; Student at the Department of Large Animal Husbandry

Malinovskaya str. 8, lit. A, Saint Petersburg, Pushkin 196602, Russian Federation

Petersburgskoye highway 2, Saint Petersburg, Pushkin 196601, Russian Federation 

kseniya.k.a@biotrof.ruhttps://orcid.org/0000-0002-6196-6226МолотковВ. В.MolotkovV. V.

 менеджер по продажам

196602, г. Санкт-Петербург, г. Пушкин, ул. Малиновская, 8, лит. А, пом. 7-Н, Россия

 Sales Manager

Malinovskaya str. 8, lit. A, Saint Petersburg, Pushkin 196602, Russian Federation

molotkov@biotrof.ruhttps://orcid.org/0000-0002-5264-1753АхматчинД. А.AkhmatchinD. A.

 менеджер по продажам

196602, г. Санкт-Петербург, г. Пушкин, ул. Малиновская, 8, лит. А, пом. 7-Н, Россия

 Sales Manager

Malinovskaya str. 8, lit. A, Saint Petersburg, Pushkin 196602, Russian Federation

da@biotrof.ruhttps://orcid.org/0000-0001-9001-2432ТюринаД. Г.TiurinaD. G.

 кандидат экономических наук, заместитель директора по финансам

196602, г. Санкт-Петербург, г. Пушкин, ул. Малиновская, 8, лит. А, пом. 7-Н, Россия

 Cand. Sc. (Econ.), Deputy Director for Finances

Malinovskaya str. 8, lit. A, Saint Petersburg, Pushkin 196602, Russian Federation 

tiurina@biotrof.ruООО «БИОТРОФ»; ФГБОУ ВО «Санкт-Петербургский государственный аграрный университет»LLC Biotrof; Saint Petersburg State Agrarian University ФГБНУ «Федеральный научный центр «Всероссийский научно-исследовательский и технологический институт птицеводства» Российской академии наукAll-Russian Research and Technological Poultry Institute of Russian Academy of Sciences ООО «БИОТРОФ»; ФГБОУ ВО «Санкт-Петербургский государственный аграрный университет»LLC Biotrof; Saint Petersburg State Agrarian UniversityООО «БИОТРОФ»LLC BiotrofООО «БИОТРОФ»LLC Biotrof 20220507202273180189Copyright © Йылдырым Е.А., Грозина А.А., Ильина Л.А., Филиппова В.А., Лаптев Г.Ю., Пономарева Е.С., Дубровин А.В., Калиткина К.А., Молотков В.В., Ахматчин Д.А., Тюрина Д.Г., 20222022Йылдырым Е.А., Грозина А.А., Ильина Л.А., Филиппова В.А., Лаптев Г.Ю., Пономарева Е.С., Дубровин А.В., Калиткина К.А., Молотков В.В., Ахматчин Д.А., Тюрина Д.Г.Yildirim E.A., Grozina A.A., Ilina L.A., Filippova V.A., Laptev G.Y., Ponomareva E.S., Dubrowin A.V., Kalitkina K.A., Molotkov V.V., Akhmatchin D.A., Tiurina D.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.actabiomedica.ru/jour/article/view/3565

Введение. Т-2 токсин, поступающий с кормами, может ингибировать функцию врождённой иммунной системы у птиц.Цель работы. Оценить влияние воздействия Т-2 токсина, искусственно внесённого с кормами, на уровень экспрессии ряда генов, связанных с иммунитетом, в тканях пищеварительной системы бройлеров.Материалы и методы. Эксперименты проводили в виварии ФНЦ «ВНИТИП» РАН на бройлерах кросса Смена 8 от 33 до 47-суточного возраста. Была выполнена экспериментальная контаминация корма Т-2 токсином. Птиц разделили на 4 группы по 5 голов в каждой: I – контрольная, получавшая рацион без введения Т-2 токсина, II опытная – получавшая рацион с добавлением Т-2 токсина, III опытная – получавшая рацион с добавлением Т-2 токсина и сорбент Заслон2+, IV опытная – получавшая рацион с добавлением Т-2 токсина, тот же сорбент Заслон2+ и фермент Axtra Pro. Уровень экспрессии мРНК анализировали методом количественной ПЦР с обратной транскрипцией.Результаты. Полученные данные свидетельствовали о воздействии загрязнения кормов бройлеров Т-2 токсином на модуляцию уровня экспрессии генов, связанных с функционированием иммунной системы, в слепых отростках кишечника и поджелудочной железы. Воздействие Т-2 токсина (группа II) привело к увеличению экспрессии провоспалительного гена IL-6 в тканях слепых отростков кишечника в 10,8 раза и IL-8 в поджелудочной железе в 3,89 раза (р ≤ 0,05) по сравнению с контрольной группой I. Влияние сорбента, а также комплекса, включающего сорбент и фермент, на экспрессию генов бройлеров, было позитивным. Сорбент без фермента показал большую эффективность, чем с дополнительным введением фермента.

Background. Feed-borne T-2 toxin may inhibit innate immune system function in birds.The aim. To evaluate the effect of T-2 toxin, artificially introduced with feed, on the expression level of a number of immunity-related genes in the tissues of the broiler digestive system.Materials and methods. The experiments were carried out in the vivarium of the FSC “VNITIP” RAS broilers of the Smena 8 cross from 33 to 47-day old. Experimental contamination of feed T-2 toxin was performed. The birds were divided into 4 groups of 5 animals each: I – control, receiving a diet without the introduction of T-2 toxin, II experimental – receiving a diet with the addition of T-2 toxin, III experimental – receiving a diet with the addition of T-2 toxin and the sorbent Zaslon2+, IV experimental – receiving a diet with the addition of T-2 toxin, the same sorbent Zaslon2+and Axtra Pro enzyme. The level of mRNA expression was analyzed by quantitative reverse transcription PCR.Results. The data obtained indicated the impact of T-2 toxin contamination of broiler feed on the modulation of the level of expression of genes associated with the functioning of the immune system in the cecum and pancreas. Exposure to T-2 toxin (group II) led to an increase in the expression of the pro-inflammatory gene IL-6 in the tissues of the caecum by 10.8 times and IL-8 in the pancreas by 3.89 times (p ≤ 0.05) compared with control group I. The effect of the sorbent, as well as the complex, including the sorbent and the enzyme, on the expression of broiler genes was positive. The sorbent without the enzyme showed greater efficiency than with the additional introduction of the enzyme.

микотоксиныТ-2 токсинбройлерыэкспрессия геновсельскохозяйственная птицасорбентферментmycotoxinsT-2 toxinbroilersgene expressionpoultrysorbentenzymeРабота выполнена при поддержке гранта РНФ 20- 76-10003.ReferencesZain ME. Impact of mycotoxins on humans and animals. J Saudi Chem Soc. 2011; 15(2): 129-144. doi: 10.1016/j.jscs.2010.06.006Zain ME. Impact of mycotoxins on humans and animals. J Saudi Chem Soc. 2011; 15(2): 129-144. doi: 10.1016/j.jscs.2010.06.006Fink-Gremmels J, Georgiou NA. Risk assessment of mycotoxins for the consumer. In: Ennen G, Kuiper HA, Valentin A (eds). Residues of veterinary drugs and mycotoxins in animal products. NL-Wageningen Press; 1996: 159-174.Fink-Gremmels J, Georgiou NA. Risk assessment of mycotoxins for the consumer. In: Ennen G, Kuiper HA, Valentin A (eds). Residues of veterinary drugs and mycotoxins in animal products. NL-Wageningen Press; 1996: 159-174.Adhikari M, Negi B, Kaushik N, Adhikari A, Al-Khedhairy AA, Kaushik NK, et al. T-2 mycotoxin: toxicological effects and decontamination strategies. Oncotarget. 2017; 8(20): 33933-33952. doi: 10.18632/oncotarget.15422Adhikari M, Negi B, Kaushik N, Adhikari A, Al-Khedhairy AA, Kaushik NK, et al. T-2 mycotoxin: toxicological effects and decontamination strategies. Oncotarget. 2017; 8(20): 33933-33952. doi: 10.18632/oncotarget.15422Kalantari H, Zong MS, Chang IM. Assay of T-2 toxin contamination in domestic and imported agricultural products in Korea. Proc Jpn Assoc Mycotoxicol. 1989; 1989(30): 32-34. doi: 10.2520/myco1975.1989.30_32Kalantari H, Zong MS, Chang IM. Assay of T-2 toxin contamination in domestic and imported agricultural products in Korea. Proc Jpn Assoc Mycotoxicol. 1989; 1989(30): 32-34. doi: 10.2520/myco1975.1989.30_32Krska R, Malachova A, BerthILler F, Egmond HPV. Determination of T-2 and HT-2 toxins in food and feed: An update. World Mycotoxin J. 2014; 7(2): 131-142. doi: 10.3920/WMJ2013.1605Krska R, Malachova A, BerthILler F, Egmond HPV. Determination of T-2 and HT-2 toxins in food and feed: An update. World Mycotoxin J. 2014; 7(2): 131-142. doi: 10.3920/WMJ2013.1605Кононенко Г.П., Буркин А.А., Зотова Е.В. Микотоксикологический мониторинг. Сообщение 3. Кормовая продукция от переработки зернового сырья. Ветеринария сегодня. 2020; 3(34): 213-219. doi: 10.29326/2304-196X-2020-3-34-213-219Kononenko GP, Burkin AA, Zotova EV. Mycotoxicological monitoring. Message 3. Feed products from the processing of grain raw materials. Veterinary Science Today. 2020; 3(34): 213-219. (In Russ.). doi: 10.29326/2304-196X-2020-3-34-213-219Akande KE, Abubakar MM, Adegbola TA, Bogoro SE. Nutritional and health implications of mycotoxins in animal feeds: A review. Pak J Nutr. 2006; 5(5): 398-403.Akande KE, Abubakar MM, Adegbola TA, Bogoro SE. Nutritional and health implications of mycotoxins in animal feeds: A review. Pak J Nutr. 2006; 5(5): 398-403.Oswald IP, Marin DE, Bouhet S, Pinton P, Taranu I, Accensi F. Immunotoxicological risk of mycotoxins for domestic animals. Food Addit Contam. 2005, 22(4): 354-360. doi: 10.1080/02652030500058320Oswald IP, Marin DE, Bouhet S, Pinton P, Taranu I, Accensi F. Immunotoxicological risk of mycotoxins for domestic animals. Food Addit Contam. 2005, 22(4): 354-360. doi: 10.1080/02652030500058320Seeboth J, Solinhac R, Oswald IP, Guzylack-Piriou L. The fungal T-2 toxin alters the activation of primary macrophages induced by TLR-agonists resulting in a decrease of the inflammatory response in the pig. Vet Res. 2012; 43: 35(2012). doi: 10.1186/1297-9716-43-35Seeboth J, Solinhac R, Oswald IP, Guzylack-Piriou L. The fungal T-2 toxin alters the activation of primary macrophages induced by TLR-agonists resulting in a decrease of the inflammatory response in the pig. Vet Res. 2012; 43: 35(2012). doi: 10.1186/1297-9716-43-35Pierron A, Alassane-Kpembi I, Oswald IP. Impact of mycotoxin on immune response and consequences for pig health. Anim Nutr. 2016; 2(2): 63-68. doi: 10.1016/j.aninu.2016.03.001Pierron A, Alassane-Kpembi I, Oswald IP. Impact of mycotoxin on immune response and consequences for pig health. Anim Nutr. 2016; 2(2): 63-68. doi: 10.1016/j.aninu.2016.03.001Wan Q, Wu G, He Q, Tang H, Wang Y. The toxicity of acute exposure to T-2 toxin evaluated by the metabonomics technique. Mol Biosyst. 2015; 11(3): 882-891. doi: 10.1039/c4mb00622dWan Q, Wu G, He Q, Tang H, Wang Y. The toxicity of acute exposure to T-2 toxin evaluated by the metabonomics technique. Mol Biosyst. 2015; 11(3): 882-891. doi: 10.1039/c4mb00622dGrenier B, Applegate TJ. Modulation of intestinal functions following mycotoxin ingestion: Meta-analysis of published experiments in animals. Toxins. 2013; 5(2): 396-430. doi: 10.3390/toxins5020396Grenier B, Applegate TJ. Modulation of intestinal functions following mycotoxin ingestion: Meta-analysis of published experiments in animals. Toxins. 2013; 5(2): 396-430. doi: 10.3390/toxins5020396Casteleyn C, Doom M, Lambrechts E, Van den Broeck W, Simoens P, Cornillie P. Locations of gut-associated lymphoid tissue in the 3-month-old chicken: A review. Avian Pathol. 2010; 39(3): 143-150. doi: 10.1080/03079451003786105Casteleyn C, Doom M, Lambrechts E, Van den Broeck W, Simoens P, Cornillie P. Locations of gut-associated lymphoid tissue in the 3-month-old chicken: A review. Avian Pathol. 2010; 39(3): 143-150. doi: 10.1080/03079451003786105Pinton P, Oswald IP. Effect of deoxynivalenol and other Type B trichothecenes on the intestine: A review. Toxins (Basel). 2014; 6(5): 1615-1643. doi: 10.3390/toxins6051615Pinton P, Oswald IP. Effect of deoxynivalenol and other Type B trichothecenes on the intestine: A review. Toxins (Basel). 2014; 6(5): 1615-1643. doi: 10.3390/toxins6051615Pang VF, Adams JH, Beasley VR, Buck WB, Haschek WM. Myocardial and pancreatic lesions induced by T-2 toxin, a trichothecene mycotoxin, in swine. Vet Pathol. 1986; 23(3): 310-319. doi: 10.1177/030098588602300312Pang VF, Adams JH, Beasley VR, Buck WB, Haschek WM. Myocardial and pancreatic lesions induced by T-2 toxin, a trichothecene mycotoxin, in swine. Vet Pathol. 1986; 23(3): 310-319. doi: 10.1177/030098588602300312Obremski K, Podlasz P, Żmigrodzka M, Winnicka A, Woźny M, Brzuza P, et al. The effect of T-2 toxin on percentages of CD4+, CD8+, CD4+CD8+ and CD21+ lymphocytes, and mRNA expression levels of selected cytokines in porcine ileal Peyer’s patches. Pol J Vet Sci. 2013; 16(2): 341-349. doi: 10.2478/pjvs-2013-0046Obremski K, Podlasz P, Żmigrodzka M, Winnicka A, Woźny M, Brzuza P, et al. The effect of T-2 toxin on percentages of CD4+, CD8+, CD4+CD8+ and CD21+ lymphocytes, and mRNA expression levels of selected cytokines in porcine ileal Peyer’s patches. Pol J Vet Sci. 2013; 16(2): 341-349. doi: 10.2478/pjvs-2013-0046Afsah-Hejri L, Jinap S, Hajeb P, Radu S, Shakibazadeh SH. A review on mycotoxins in food and feed: Malaysia case study. Compr Rev Food Sci Food Saf. 2013; 12(6): 629-651. doi: 10.1111/1541-4337.12029Afsah-Hejri L, Jinap S, Hajeb P, Radu S, Shakibazadeh SH. A review on mycotoxins in food and feed: Malaysia case study. Com pr Rev Food Sci Food Saf. 2013; 12(6): 629-651. doi: 10.1111/1541-4337.12029Hritzo Ahye MK, Golding A. Cytoplasmic FOXO1 identifies a novel disease-activity associated B cell phenotype in SLE. Lupus Sci Med. 2018; 5(1): e000296. doi: 10.1136/lupus-2018-000296Hritzo Ahye MK, Golding A. Cytoplasmic FOXO1 identifies a novel disease-activity associated B cell phenotype in SLE. Lupus Sci Med. 2018; 5(1): e000296. doi: 10.1136/lupus-2018-000296Bijl M, Horst G, Limburg PC, Kallenberg CG. Fas expression on peripheral blood lymphocytes in systemic lupus erythematosus (SLE): Relation to lymphocyte activation and disease activity. Lupus. 2001; 10(12): 866-872. doi: 10.1191/096120301701548517Bijl M, Horst G, Limburg PC, Kallenberg CG. Fas expression on peripheral blood lymphocytes in systemic lupus erythematosus (SLE): Relation to lymphocyte activation and disease activity. Lupus. 2001; 10(12): 866-872. doi: 10.1191/096120301701548517Wilk AJ, Rustagi A, Zhao NQ, Roque J, Martínez-Colón GJ, McKechnie JL, et al. A single-cell atlas of the peripheral immune response in patients with severe COVID-19. Nat Med. 2020; 26(7): 1070-1076. doi: 10.1038/s41591-020-0944-yWilk AJ, Rustagi A, Zhao NQ, Roque J, Martínez-Colón GJ, McKechnie JL, et al. A single-cell atlas of the peripheral immune response in patients with severe COVID-19. Nat Med. 2020; 26(7): 1070-1076. doi: 10.1038/s41591-020-0944-yJones D, Como CN, Jing L, Blackmon A, Neff CP, Krueger O, et al. Varicella zoster virus productively infects human peripheral blood mononuclear cells to modulate expression of immunoinhibitory proteins and blocking PD-L1 enhances virus-specific CD8+ T cell effector function. PLoS Pathog. 2019; 15(3): e1007650. doi: 10.1371/journal.ppat.1007650Jones D, Como CN, Jing L, Blackmon A, Neff CP, Krueger O, et al. Varicella zoster virus productively infects human peripheral blood mononuclear cells to modulate expression of immunoinhibitory proteins and blocking PD-L1 enhances virus-specific CD8+ T cell effector function. PLoS Pathog. 2019; 15(3): e1007650. doi: 10.1371/journal.ppat.1007650Guilford FT, Hope J. Deficient glutathione in the pathophysiology of mycotoxin-related illness. Toxins (Basel). 2014; 6(2): 608-623. doi: 10.3390/toxins6020608Guilford FT, Hope J. Deficient glutathione in the pathophysiology of mycotoxin-related illness. Toxins (Basel). 2014; 6(2): 608-623. doi: 10.3390/toxins6020608Li Y, Zhang J, Wu Y, Liu G, Song L, Li Y, et al. High-sensitive chemiluminescent immunoassay investigation and application for the detection of T-2 toxin and major metabolite HT-2 toxin. J Sci Food Agric. 2017; 97(3): 818-822. doi: 10.1002/jsfa.7801Li Y, Zhang J, Wu Y, Liu G, Song L, Li Y, et al. High-sensitive chemiluminescent immunoassay investigation and application for the detection of T-2 toxin and major metabolite HT-2 toxin. J Sci Food Agric. 2017; 97(3): 818-822. doi: 10.1002/jsfa.7801Liu YL, Meng G.Q, Wang HR, Zhu HL, Hou YQ, Wang WJ, et al. Effect of three mycotoxin adsorbents on growth performance, nutrient retention and meat quality in broilers fed on mouldcontaminated feed. Br Poult Sci. 2011; 52(2): 255-263. doi: 10.1080/00071668.2011.559453Liu YL, Meng G.Q, Wang HR, Zhu HL, Hou YQ, Wang WJ, et al. Effect of three mycotoxin adsorbents on growth performance, nutrient retention and meat quality in broilers fed on mouldcontaminated feed. Br Poult Sci. 2011; 52(2): 255-263. doi: 10.1080/00071668.2011.559453Tozaki H, Emi Y, Horisaka E, Fujita T, Yamamoto A, Muranishi S. Degradation of insulin and calcitonin and their protection by various protease inhibitors in rat caecal contents: Implications in peptide delivery to the colon. J Pharm Pharmacol. 1997; 49(2): 164-168. doi: 10.1111/j.2042-7158.1997.tb06773.xTozaki H, Emi Y, Horisaka E, Fujita T, Yamamoto A, Muranishi S. Degradation of insulin and calcitonin and their protection by various protease inhibitors in rat caecal contents: Implications in peptide delivery to the colon. J Pharm Pharmacol. 1997; 49(2): 164-168. doi: 10.1111/j.2042-7158.1997.tb06773.xЕвропейская конвенция о защите позвоночных животных, используемых для экспериментов или в других научных целях (ETS № 123). Страсбург; 1986. URL: https://rm.coe.int/168007a6a8 [дата доступа: 15.02.2022].European Convention for the Protection of Vertebrate Animals used for Experimental or Other Scientific Purposes (ETS No. 123). Strasbourg; 1986. URL: https://rm.coe.int/168007a6a8 [date of access: 15.02.2022]. (In Russ.)Егоров И.А., Манукян В.А., Ленкова Т.Н., Околелова Т.М., Лукашенко В.С., Шевяков А.Н. и др. Методика проведения научных и производственных исследований по кормлению сельскохозяйственной птицы. Молекулярно-генетические методы определения микрофлоры кишечника. Под ред. В.И. Фисинина. Сергиев Посад; 2013.Egorov IA, Manukyan VA, Lenkova TN, Okolelova TM, Lukashenko VS, Shevyakov AN, et al. Methods for conducting scientific and industrial research on feeding poultry. Molecular genetic methods for determining the intestinal microflora. Sergiev Posad; 2013. (In Russ.).Zeka F, Vanderheyden K, Smet E, Cuvelier C, Mestdagh P, Vandesompele J. Straightforward and sensitive RT-qPCR based gene expression analysis of FFPE samples. Sci Rep. 2016; 6: 21418. doi: 10.1038/srep21418Zeka F, Vanderheyden K, Smet E, Cuvelier C, Mestdagh P, Vandesompele J. Straightforward and sensitive RT-qPCR based gene expression analysis of FFPE samples. Sci Rep. 2016; 6: 21418. doi: 10.1038/srep21418Meza Cerda MI, Gray R, Higgins DP. Cytokine RT-qPCR and ddPCR for immunological investigations of the endangered Australian sea lion (Neophoca cinerea) and other mammals. Peer J. 2020; 8: e10306. doi: 10.7717/peerj.10306Meza Cerda MI, Gray R, Higgins DP. Cytokine RT-qPCR and ddPCR for immunological investigations of the endangered Australian sea lion (Neophoca cinerea) and other mammals. Peer J. 2020; 8: e10306. doi: 10.7717/peerj.10306Laptev GY, Filippova VA, Kochish II, Yildirim EA, Ilina LA, Dubrovin AV, et al. Examination of the expression of immunity genes and bacterial profiles in the caecum of growing chickens infected with Salmonella enteritidis and fed a phytobiotic. Animals (Basel). 2019; 9(9): 615. doi: 10.3390/ani9090615Laptev GY, Filippova VA, Kochish II, Yildirim EA, Ilina LA, Dubrovin AV, et al. Examination of the expression of immunity genes and bacterial profiles in the caecum of growing chickens infected with Salmonella enteritidis and fed a phytobiotic. Animals (Basel). 2019; 9(9): 615. doi: 10.3390/ani9090615Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001; 25(4): 402-408. doi: 10.1006/meth.2001.1262Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods.2001;25(4): 402-408. doi: 10.1006/meth.2001.1262Йылдырым Е.А., Грозина А.А., Вертипрахов В.Г., Ильина Л.А., Филиппова В.А., Лаптев Г.Ю., и др. Экспрессия генов, ассоциированных с иммунитетом, в тканях слепых отростков кишечника и поджелудочной железы цыплят-бройлеров (Gallus Gallus L.) при экспериментальном Т-2 токсикозе. Сельскохозяйственная биология. 2021; 56(4): 664-681. doi: 10.15389/agrobiology.2021.4.664rusYildyrym EA, Grozina AA, Vertiprakhov VG, Ilyina LA, Filippova VA, Laptev GYu, et al. Expression of immune-associated genes in tissues blind processes of the intestine and pancreas of broiler chickens (Gallus Gallus L.) with experimental T-2 toxicosis. Sel’skokhozyaistvennaya biologiya. 2021; 56(4): 664-681. (In Russ.). doi: 10.15389/agrobiology.2021.4.664rusLiu SD, Song MH, Yun W, Lee JH, Kim HB, Cho JH. Effect of carvacrol essential oils on immune response and inflammationrelated genes expression in broilers challenged by lipopolysaccharide. Poult Sci. 2019; 98(5): 2026-2033. doi: 10.3382/ps/pey575Liu SD, Song MH, Yun W, Lee JH, Kim HB, Cho JH. Effect of carvacrol essential oils on immune response and inflammationrelated genes expression in broilers challenged by lipopolysaccharide. Poult Sci. 2019; 98(5): 2026-2033. doi: 10.3382/ps/pey575Lotze ATM. The cytokine handbook. 4th ed. Academic Press; 2003.Lotze ATM. The cytokine handbook. 4th ed. Academic Press; 2003.Broom LJ, Kogut MH. Inflammation: friend or foe for animal production? Poultry Science. 2018; 97(2): 510-514. doi: 10.3382/ps/pex314Broom LJ, Kogut MH. Inflammation: friend or foe for animal production? Poultry Science. 2018; 97(2): 510-514. doi: 10.3382/ps/pex314Jiang XR, Awati A, Agazzi A, Vitari F, Ferrari A, Bento H, et al. Effects of a blend of essential oils and an enzyme combination on nutrient digestibility, ileum histology and expression of inflammatory mediators in weaned piglets. Аnimal. 2015; 9(3): 417-426. doi: 10.1017/S1751731114002444Jiang XR, Awati A, Agazzi A, Vitari F, Ferrari A, Bento H, et al. Effects of a blend of essential oils and an enzyme combination on nutrient digestibility, ileum histology and expression of inflammatory mediators in weaned piglets. Аnimal. 2015; 9(3): 417-426. doi: 10.1017/S1751731114002444Alnemri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornberry NA, Wong WW, et al. Human ICE/CED-3 protease nomenclature. Cell. 1996; 87(2): 171. doi: 10.1016/s0092-8674(00)81334-3Alnemri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornberry NA, Wong WW, et al. Human ICE/CED-3 protease nomenclature. Cell. 1996; 87(2): 171. doi: 10.1016/s0092-8674(00)81334-3Zhivotovsky B, Burgess DH, Orrenius S. Proteases in apoptosis. Experientia. 1996; 52(10-11): 968-978. doi: 10.1007/BF01920106Zhivotovsky B, Burgess DH, Orrenius S. Proteases in apoptosis. Experientia. 1996; 52(10-11): 968-978. doi: 10.1007/BF01920106Wu B, Guo H, Cui H, Peng X, Fang J, Zuo Z, et al. Pathway underlying small intestine apoptosis by dietary nickel chloride in broiler chickens. Chemic Biol Interact. 2016; 243: 91-106. doi: 10.1016/j.cbi.2015.11.010Wu B, Guo H, Cui H, Peng X, Fang J, Zuo Z, et al. Pathway underlying small intestine apoptosis by dietary nickel chloride in broiler chickens. Chemic Biol Interact. 2016; 243: 91-106. doi: 10.1016/j.cbi.2015.11.010van Dijk A, Veldhuizen EJA, Haagsman HP. Avian defensins. Vet Immunol Immunopathol. 2008; 124(1-2): 1-18. doi: 10.1016/j.vetimm.2007.12.006van Dijk A, Veldhuizen EJA, Haagsman HP. Avian defensins. Vet Immunol Immunopathol. 2008; 124(1-2): 1-18. doi: 10.1016/j.vetimm.2007.12.006Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J, et al. Beta-defensins: Linking innate and adaptive immunity through dendritic and T cell CCR6. Science. 1999; 286(5439): 525-528. doi: 10.1126/science.286.5439.525Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J, et al. Beta-defensins: Linking innate and adaptive immunity through dendritic and T cell CCR6. Science. 1999; 286(5439): 525-528. doi: 10.1126/science.286.5439.525Niyonsaba F, Iwabuchi K, Matsuda H, Ogawa H, Nagaoka I. Epithelial cell-derived human beta-defensin-2 acts as a chemotaxin for mast cells through a pertussis toxin-sensitive and phospholipase C-dependent pathway. Int Immunol. 2002; 14(4): 421-426. doi: 10.1093/intimm/14.4.421Niyonsaba F, Iwabuchi K, Matsuda H, Ogawa H, Nagaoka I. Epithelial cell-derived human beta-defensin-2 acts as a chemotaxin for mast cells through a pertussis toxin-sensitive and phospholipase C-dependent pathway. Int Immunol. 2002; 14(4): 421-426. doi: 10.1093/intimm/14.4.421Veldhuizen EJA, Hendriks HG, Hogenkamp A, van Dijk A, Gaastra W, Tooten PCJ, et al. Differential regulation of porcine β-defensins 1 and 2 upon Salmonella infection in the intestinal epithelial cell line IPI-2I. Vet Immunol Immunopathol. 2006; 114(1-2): 94-102. doi: 10.1016/j.vetimm.2006.07.012Veldhuizen EJA, Hendriks HG, Hogenkamp A, van Dijk A, Gaastra W, Tooten PCJ, et al. Differential regulation of porcine β-defensins 1 and 2 upon Salmonella infection in the intestinal epithelial cell line IPI-2I. Vet Immunol Immunopathol. 2006; 114(1-2): 94-102. doi: 10.1016/j.vetimm.2006.07.012Elahi S, Buchanan RM, Attah-Poku S, Townsend HGG, Babiuk LA, Gerdts V. The host defense peptide beta-defensin 1 confers protection against Bordetella pertussis in newborn piglets. Infect Immun. 2006; 74(4): 2338-2352. doi: 10.1128/IAI.74.4.2338-2352.2006Elahi S, Buchanan RM, Attah-Poku S, Townsend HGG, Babiuk LA, Gerdts V. The host defense peptide beta-defensin 1 confers protection against Bordetella pertussis in newborn piglets. Infect Immun. 2006; 74(4): 2338-2352. doi: 10.1128/IAI.74.4.2338-2352.2006Zhang G, Hiraiwa H, Yasue H, Wu H, Ross CR, Troyer D, et al. Cloning and characterization of the gene for a new epithelial α-defensin. J Biol Chem. 1999; 274(34): 24031-24037. doi: 10.1074/jbc.274.34.24031Zhang G, Hiraiwa H, Yasue H, Wu H, Ross CR, Troyer D, et al. Cloning and characterization of the gene for a new epithelial α-defensin. J Biol Chem. 1999; 274(34): 24031-24037. doi: 10.1074/jbc.274.34.24031Veldhuizen EJA., Rijnders M, Claassen EA, van Dijk A, Haagsman HP. Porcine α-defensin 2 displays broad antimicrobial activity against pathogenic intestinal bacteria. Mol Immunol. 2008; 45(2): 386-394. doi: 10.1016/j.molimm.2007.06.001Veldhuizen EJA., Rijnders M, Claassen EA, van Dijk A, Haagsman HP. Porcine α-defensin 2 displays broad antimicrobial activity against pathogenic intestinal bacteria. Mol Immunol. 2008; 45(2): 386-394. doi: 10.1016/j.molimm.2007.06.001

The authors declare that there are no conflicts of interest present.