medlitГигиена и санитарияHygiene and Sanitation0016-99002412-0650Federal Scientific Center of Hygiene named after F.F. Erisman10.47470/0016-9900-2019-98-9-1021-1025medlit-411Research ArticleМЕТОДЫ ИССЛЕДОВАНИЙMETHODS OF INVESTIGATIONSИзменение профиля экспрессии генов адаптивного ответа при токсических гепатитах различной этиологииChange of the profile of expression of adaptive response genes in toxic hepatitis of different etiologyКаримовДенис ОлеговичKarimovDenis O.

MD, Ph.D., head of the department of toxicology and genetics with an experimental clinic of laboratory animals professor, head of Department of General Hygiene of Ufa Research Institute of Occupational Health and Human Ecology, Ufa, 450106, Russian Federation.

e-mail: karimovdo@gmail.com

karimovdo@gmail.comКутлинаТ. Г.KutlinaT. G.noemail@neicon.ruМухаммадиеваГ. Ф.MukhammadiyevaG. F.noemail@neicon.ruВаловаЯ. В.ValovaY. V.noemail@neicon.ruРепинаЭ. Ф.RepinaE. F.noemail@neicon.ruХуснутдиноваН. Ю.KhusnutdinovaN. Yu.noemail@neicon.ruФедеральное бюджетное учреждение науки «Уфимский научно-исследовательский институт медицины труда и экологии человека»Ufa Research Institute of Occupational Health and Human Ecology20191410202098910211025Copyright © Каримов Д.О., Кутлина Т.Г., Мухаммадиева Г.Ф., Валова Я.В., Репина Э.Ф., Хуснутдинова Н.Ю., 20202020Каримов Д.О., Кутлина Т.Г., Мухаммадиева Г.Ф., Валова Я.В., Репина Э.Ф., Хуснутдинова Н.Ю.Karimov D.O., Kutlina T.G., Mukhammadiyeva G.F., Valova Y.V., Repina E.F., Khusnutdinova N.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rjhas.ru/jour/article/view/411Введение

Введение. В России большую актуальность приобрела проблема токсических гепатитов. Этиология токсических гепатитов (промышленные токсиканты, лекарственные средства, этанол) и, как следствие, патогенез могут иметь значительные различия на молекулярно-генетическом уровне. Цель исследования заключалась в анализе экспрессии генов, задействованных в ответе на токсическое повреждение печени различной этиологии.

Материал и методы

Материал и методы. Моделирование острого токсического гепатита производилось на самцах белых беспородных крыс массой 180–200 г, разделённых на 4 группы (контрольная группа, тетрахлорметан, парацетамол, этанол). Через 24 и 72 ч после введения токсиканта крыс наркотизировали и исследовали уровни мРНК генов Chek1, Gclc, Gstm1, Gstp1, Gstt1, Nfe2l2, Nqo1, Ripk1 в гомогенате печени.

Результаты

Результаты. В результате проведённого анализа экспрессии изучаемых генов было обнаружено, что профиль экспрессии отличался в зависимости от этиологии токсического гепатита. При отравлении тетрахлорметаном наблюдалось повышение экспрессии генов Nqo1 (p = 0,001), Gstm1 (p = 0,037) и снижение экспрессии генов Nfe2l2 (p = 0,004), Ripk1 (p = 0,004). При поражении печени парацетамолом и его метаболитами, напротив, экспрессия гена Gstm1 (p = 0,001) снижалась, а экспрессия генов Nfe2l2 (p = 0,009), Gclc (p = 0,001), Chek1 (p = 0,011) – повышалась. При алкогольной интоксикации статистически значимых изменений в профиле экспрессии изучаемых генов не наблюдалось.

Заключение

Заключение. Полученные результаты могут указывать на участие различных молекулярно-генетических механизмов в процессе ответа на токсическое повреждение печени в зависимости от этиологии.

Introduction

Introduction. In Russia, the problem of toxic hepatitis is of great importance and relevance. The etiology of toxic hepatitis (industrial toxicants, drugs, ethanol) and, as a consequence, pathogenesis may have significant differences at the molecular genetic level.

The aim of the study was to analyze the expression of genes involved in the response to toxic liver damage of various etiologies.

Material and methods

Material and methods. Toxic hepatitis was modulated in male albino mongrel rats weighing 180-200 grams assigned to four groups (control group, carbon tetrachloride, paracetamol, ethanol). After 24 and 72 hours of paracetamol administration, rats were anesthetized and the mRNA levels of the Chek1, Gclc, Gstm1, Gstp1, Gstt1, Nfe2l2, Nqo1, Ripk1 genes in the liver homogenate were examined.

Results

Results. As a result of the analysis of the genes expression studied, the expression profile was found TO be differed depending on the etiology of toxic hepatitis. With carbon tetrachloride poisoning, an increase in the expression of the Nqo1 genes (p = 0.001), Gstm1 (p = 0.037) and a decrease in the expression of the Nfe2l2 genes (p = 0.004), Ripk1 (p = 0.004) was observed. With the liver damage by paracetamol and its metabolites, opposite to the expression of the Gstm1 gene (p = 0.001) decreased, and the expression of the Nfe2l2 (p = 0.009), Gclc (p = 0.001), Chek1 (p = 0.011) genes increased. During alcohol intoxication, there were no statistically significant changes in the expression profiles of the genes studied.

Conclusion

Conclusion. the results obtained may indicate the involvement of various molecular genetic mechanisms in the process of response to toxic liver damage, depending on the etiology.

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