Изменения показателей прооксидантной и антиоксидантной систем в плазме крови у мужчин при атрофическом гастрите и раке желудка
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Материалы и методы. Обследовано 60 практически здоровых мужчин, 42 больных атрофическим гастритом и 50 мужчин, больных некардиальным раком желудка II стадии по TNM. Всем пациентам выполнялась серологическая диагностика диффузного атрофического гастрита (определение пепсиногенов и гастрина-17) и инфекции Helicobacter pylori. Диагноз «атрофический гастрит» верифицировался морфологическим исследованием биоптатов, полученных во время фиброэзофагогастродуоденоскопии. Диагностика рака желудка осуществлялась в Красноярском краевом онкологическом диспансере на основании комплексного инструментального и морфологического обследования. Всем пациентам спектрофотометрическими методами в плазме крови определяли содержание диеновых конъюгатов (ДК), малонового диальдегида (МДА), глутатион-S-трансферазы (ГСТ), глутатионпероксидазы (ГПО), супероксиддисмутазы (СОД) и каталазы.
Результаты. Концентрация СОД, ГСТ, ГПО и каталазы не имела существенных различий у больных атрофическим гастритом и раком желудка и превалировала в сравнении со здоровыми лицами. У больных раком желудка содержание в плазме крови ДК в 2,7 раза и МДА в 35,2 раза превышало аналогичные показатели здоровых лиц, что свидетельствовало о выраженном оксидативном стрессе у пациентов с онкологической патологией. У пациентов с атрофическим гастритом наблюдалась аналогичная, но менее выраженная закономерность.
Заключение. Полученные результаты свидетельствуют о наличии проявлений оксидативного стресса у мужчин с атрофическим гастритом и раком желудка.
Ключевые слова: атрофический гастрит, рак желудка, оксидативный стресс, перекисное окисление липидов, антиоксидантная защита, Helicobacter pylori.
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Aim. To study changes in the indices of prooxidant and antioxidant systems in plasma in men with atrophic gastritis and gastric cancer.
Materials and methods. The study included 60 healthy men, 42 patients with atrophic gastritis and 50 men, nicardipine patients with gastric cancer stage II according to TNM. All patients underwent serological diagnosis of diffuse atrophic gastritis (definition of pepsinogens and gastrin-17) and Helicobacter pylori infection. The diagnosis of "atrophic gastritis" was verified by morphological examination of biopsy specimens obtained during fibroesophagogastroduodenoscopy. Diagnosis of gastric cancer was carried out in the Krasnoyarsk regional oncologic dispensary on the basis of a comprehensive instrumental and morphological examination. All patients spectrophotometric methods in plasma was determined the content of diene conjugates (DC), malonic dialdehyde (MDA), glutathione-S-transferase (GST), glutathione peroxidase (GPO), superoxide dismutase (SOD) and catalase.
Results. The concentration of SOD, GST, GPO and catalase had no significant differences in patients with atrophic gastritis and gastric cancer and prevailed in comparison with healthy persons. Patients with cancer of the stomach content in the blood plasma DK 2.7 times and MDA at 35.2 times higher than healthy individuals, indicating severe oxidative stress in patients with cancer. In patients with atrophic gastritis was observed similar but less pronounced pattern.
Conclusion. The results indicate the presence of oxidative stress in men with atrophic gastritis and gastric cancer.
Keywords: atrophic gastritis, gastric cancer, oxidative stress, lipid peroxidation, antioxidant protection, Helicobacter pylori.
2. Correa P. Gastric cancer: overview. Gastroenterol Clin North Am. 2013;42(2):211-7. doi: 10.1016/j.gtc.2013.01.002
3. Цуканов В.В., Амельчугова О.С., Каспаров Э.В., Буторин Н.Н., Васютин А.В., Тонких Ю.Л., Третьякова О.В. Роль эрадикации Helicobacter pylori в профилактике рака желудка. Терапевтический архив. 2014;86(8):124-7 [Tsukanov VV, Amel'chugova OS, Kasparov ÉV, Butorin NN, Vasiutin AV, Tonkikh IuL, Tret'iakova OV. Role of Helicobacter pylori eradication in the prevention of gastric cancer. Terapevticheskiy Arkhiv. 2014;86(8):124-7 (In Russ.)].
4. Graham DY. Helicobacter pylori update: gastric cancer, reliable therapy, and possible benefits. Gastroenterology. 2015;148(4):719-31. doi: 10.1053/ j.gastro.2015.01.040
5. Агеева Е.С., Штыгашева О.В., Рязанцева Н.В., Цуканов В.В. Молекулярно-генетические факторы, влияющие на исход инфицирования Helicobacter pylori у жителей Республики Хакасия Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2010; 20(4):25-30 [Ageyeva ЕS, Shtygasheva OV, Ryazantseva NV, Tsukanov VV. Molecular-genetic factors affecting the outcome of Helicobacter pylori infection in the inhabitants of the Republic of Khakassia. Rossiyskiy Zhurnal Gastroenterologii, Gepatologii, Koloproktologii. 2010;20(4):25-30 (In Russ.)].
6. Цуканов В.В., Третьякова О.В., Амельчугова О.С., Каспаров Э.В., Родина Д.В., Васютин А.В., Буторин Н.Н., Тонких Ю.Л. Распространенность атрофического гастрита тела желудка у населения г. Красноярска старше 45 лет. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2012;22(4):27-31 [Tsukanov VV, Tret'yakova OV, Amel'chugova OS, Kasparov EV, Rodina DV, Vasyutin AV, Butorin NN, Tonkikh JL. The prevalence of atrophic gastritis of the body of the stomach in the population of Krasnoyarsk is over 45 years old. Rossiyskiy Zhurnal Gastroenterologii, Gepatologii, Koloproktologii. 2012;22(4):27-31 (In Russ.)].
7. Sugano K, Tack J, Kuipers EJ, Graham DY, El-Omar EM, Miura S, Haruma K, Asaka M, Uemura N, Malfertheiner P. Kyoto global consensus report on Helicobacter pylori gastritis. Gut. 2015;64(9):1353-67. doi: 10.1136/ gutjnl-2015-309252
8. Tsukanov VV, Butorin NN, Maady AS, Shtygasheva OV, Amelchugo-
va OS, Tonkikh JL, Fassan M, Rugge M. Helicobacter pylori Infection, Intestinal Metaplasia, and Gastric Cancer Risk in Eastern Siberia. Helicobacter. 2011;16(2):107-12. doi: 10.1111/j.1523-5378.2011.00827.x
9. Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 1996;20(10):1161-81. doi: 10.1097/00000478-199610000-00001
10. Situnayake RD, Crump BJ, Zezulka AV, Davis M, McConkey B, Thurnham DI. Measurement of conjugated diene lipids by derivative spectroscopy in heptane extracts of plasma. Ann Clin Biochem. 1990;27(Pt 3):258-66. doi: 10.1177/000456329002700313
11. Li XY, Chow CK. An improved method for the measurement of malondialdehyde in biological samples. Lipids. 1994;29(1):73-5.
doi: 10.1007/bf02537094
12. Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem. 1974;249(22):7130-9.
13. Mannervik B. Glutathione Peroxidase. In: Wiley Encyclopedia of Molecular Medicine. John Wiley & Sons, Inc.; 2002 Jan 15. doi: 10.1002/ 0471203076.emm1273
14. Sun M, Zigman S. An improved spectrophotometric assay for superoxide dismutase based on epinephrine autoxidation. Anal Biochem. 1978;90(1):81-9. doi: 10.1016/0003-2697(78)90010-6
15. Goth L. A simple method for determination of serum catalase activity and revision of reference range. Clin Chim Acta. 1991;196(2-3):143-51. doi: 10.1016/0009-8981(91)90067-m
16. Drake IM, Davies MJ, Mapstone NP, Dixon MF, Schorah CJ, White KL, Chalmers DM, Axon AT. Ascorbic acid may protect against human gastric cancer by scavenging mucosal oxygen radicals. Carcinogenesis. 1996 Mar;17(3):559-62. doi: 10.1093/carcin/17.3.559
17. Na HK, Woo JH. Helicobacter pylori Induces Hypermethylation of CpG Islands Through Upregulation of DNA Methyltransferase: Possible Involvement of Reactive Oxygen/Nitrogen Species. J Cancer Prev. 2014;19(4):259-64. doi: 10.15430/JCP.2014.19.4.259
18. Yanaka A. Sulforaphane enhances protection and repair of gastric mucosa against oxidative stress in vitro, and demonstrates anti-inflammatory effects on Helicobacter pylori-infected gastric mucosae in mice and human subjects. Curr Pharm Des. 2011;17(16):1532-40.
doi: 10.2174/138161211796196945
19. Backert S, Neddermann M, Maubach G, Naumann M. Pathogenesis of Helicobacter pylori infection. Helicobacter. 2016;21 Suppl.1:19-25. doi: 10.1111/hel.12335
20. Varbanova M, Frauenschläger K, Malfertheiner P. Chronic gastritis – an update. Best Pract Res Clin Gastroenterol. 2014;28(6):1031-42. doi: 10.1016/j.bpg.2014.10.005
21. Posselt G, Backert S, Wessler S. The functional interplay of Helicobacter pylori factors with gastric epithelial cells induces a multi-step process in pathogenesis. Cell Commun Signal. 2013;11:77.
doi: 10.1186/1478-811X-11-77
22. De Falco M, Lucariello A, Iaquinto S, Esposito V, Guerra G, De Luca A. Molecular Mechanisms of Helicobacter pylori Pathogenesis. J Cell Physiol. 2015;230(8):1702-7. doi: 10.1002/jcp.24933
23. Valenzuela MA, Canales J, Corvalán AH, Quest AF. Helicobacter pylori-induced inflammation and epigenetic changes during gastric carcinogenesis. World J Gastroenterol. 2015;21(45):12742-56.
doi: 10.3748/wjg.v21.i45.12742
24. Zhang RG, Duan GC, Fan QT, Chen SY. Role of Helicobacter pylori infection in pathogenesis of gastric carcinoma. World J Gastrointest Pathophysiol. 2016;7(1):97-107. doi: 10.4291/wjgp.v7.i1.97
25. Buommino E, Donnarumma G, Manente L, De Filippis A, Silvestri F, Iaquinto S, Tufano MA, De Luca A. The Helicobacter pylori protein HspB interferes with Nrf2/Keap1 pathway altering the antioxidant response of Ags cells. Helicobacter. 2012;17(6):417-25.
doi: 10.1111/j.1523-5378.2012.00973.x
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1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893-917. doi: 10.1002/ijc.25516
2. Correa P. Gastric cancer: overview. Gastroenterol Clin North Am. 2013;42(2):211-7. doi: 10.1016/j.gtc.2013.01.002
3. Tsukanov VV, Amel'chugova OS, Kasparov ÉV, Butorin NN, Vasiutin AV, Tonkikh IuL, Tret'iakova OV. Role of Helicobacter pylori eradication in the prevention of gastric cancer. Terapevticheskiy Arkhiv. 2014;86(8):124-7 (In Russ.)
4. Graham DY. Helicobacter pylori update: gastric cancer, reliable therapy, and possible benefits. Gastroenterology. 2015;148(4):719-31. doi: 10.1053/ j.gastro.2015.01.040
5. Ageyeva ЕS, Shtygasheva OV, Ryazantseva NV, Tsukanov VV. Molecular-genetic factors affecting the outcome of Helicobacter pylori infection in the inhabitants of the Republic of Khakassia. Rossiyskiy Zhurnal Gastroenterologii, Gepatologii, Koloproktologii. 2010;20(4):25-30 (In Russ.)
6. Tsukanov VV, Tret'yakova OV, Amel'chugova OS, Kasparov EV, Rodina DV, Vasyutin AV, Butorin NN, Tonkikh JL. The prevalence of atrophic gastritis of the body of the stomach in the population of Krasnoyarsk is over 45 years old. Rossiyskiy Zhurnal Gastroenterologii, Gepatologii, Koloproktologii. 2012;22(4):27-31 (In Russ.)
7. Sugano K, Tack J, Kuipers EJ, Graham DY, El-Omar EM, Miura S, Haruma K, Asaka M, Uemura N, Malfertheiner P. Kyoto global consensus report on Helicobacter pylori gastritis. Gut. 2015;64(9):1353-67. doi: 10.1136/ gutjnl-2015-309252
8. Tsukanov VV, Butorin NN, Maady AS, Shtygasheva OV, Amelchugo-
va OS, Tonkikh JL, Fassan M, Rugge M. Helicobacter pylori Infection, Intestinal Metaplasia, and Gastric Cancer Risk in Eastern Siberia. Helicobacter. 2011;16(2):107-12. doi: 10.1111/j.1523-5378.2011.00827.x
9. Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 1996;20(10):1161-81. doi: 10.1097/00000478-199610000-00001
10. Situnayake RD, Crump BJ, Zezulka AV, Davis M, McConkey B, Thurnham DI. Measurement of conjugated diene lipids by derivative spectroscopy in heptane extracts of plasma. Ann Clin Biochem. 1990;27(Pt 3):258-66. doi: 10.1177/000456329002700313
11. Li XY, Chow CK. An improved method for the measurement of malondialdehyde in biological samples. Lipids. 1994;29(1):73-5.
doi: 10.1007/bf02537094
12. Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem. 1974;249(22):7130-9.
13. Mannervik B. Glutathione Peroxidase. In: Wiley Encyclopedia of Molecular Medicine. John Wiley & Sons, Inc.; 2002 Jan 15. doi: 10.1002/ 0471203076.emm1273
14. Sun M, Zigman S. An improved spectrophotometric assay for superoxide dismutase based on epinephrine autoxidation. Anal Biochem. 1978;90(1):81-9. doi: 10.1016/0003-2697(78)90010-6
15. Goth L. A simple method for determination of serum catalase activity and revision of reference range. Clin Chim Acta. 1991;196(2-3):143-51. doi: 10.1016/0009-8981(91)90067-m
16. Drake IM, Davies MJ, Mapstone NP, Dixon MF, Schorah CJ, White KL, Chalmers DM, Axon AT. Ascorbic acid may protect against human gastric cancer by scavenging mucosal oxygen radicals. Carcinogenesis. 1996 Mar;17(3):559-62. doi: 10.1093/carcin/17.3.559
17. Na HK, Woo JH. Helicobacter pylori Induces Hypermethylation of CpG Islands Through Upregulation of DNA Methyltransferase: Possible Involvement of Reactive Oxygen/Nitrogen Species. J Cancer Prev. 2014;19(4):259-64. doi: 10.15430/JCP.2014.19.4.259
18. Yanaka A. Sulforaphane enhances protection and repair of gastric mucosa against oxidative stress in vitro, and demonstrates anti-inflammatory effects on Helicobacter pylori-infected gastric mucosae in mice and human subjects. Curr Pharm Des. 2011;17(16):1532-40.
doi: 10.2174/138161211796196945
19. Backert S, Neddermann M, Maubach G, Naumann M. Pathogenesis of Helicobacter pylori infection. Helicobacter. 2016;21 Suppl.1:19-25. doi: 10.1111/hel.12335
20. Varbanova M, Frauenschläger K, Malfertheiner P. Chronic gastritis – an update. Best Pract Res Clin Gastroenterol. 2014;28(6):1031-42. doi: 10.1016/j.bpg.2014.10.005
21. Posselt G, Backert S, Wessler S. The functional interplay of Helicobacter pylori factors with gastric epithelial cells induces a multi-step process in pathogenesis. Cell Commun Signal. 2013;11:77.
doi: 10.1186/1478-811X-11-77
22. De Falco M, Lucariello A, Iaquinto S, Esposito V, Guerra G, De Luca A. Molecular Mechanisms of Helicobacter pylori Pathogenesis. J Cell Physiol. 2015;230(8):1702-7. doi: 10.1002/jcp.24933
23. Valenzuela MA, Canales J, Corvalán AH, Quest AF. Helicobacter pylori-induced inflammation and epigenetic changes during gastric carcinogenesis. World J Gastroenterol. 2015;21(45):12742-56.
doi: 10.3748/wjg.v21.i45.12742
24. Zhang RG, Duan GC, Fan QT, Chen SY. Role of Helicobacter pylori infection in pathogenesis of gastric carcinoma. World J Gastrointest Pathophysiol. 2016;7(1):97-107. doi: 10.4291/wjgp.v7.i1.97
25. Buommino E, Donnarumma G, Manente L, De Filippis A, Silvestri F, Iaquinto S, Tufano MA, De Luca A. The Helicobacter pylori protein HspB interferes with Nrf2/Keap1 pathway altering the antioxidant response of Ags cells. Helicobacter. 2012;17(6):417-25.
doi: 10.1111/j.1523-5378.2012.00973.x
ФГБНУ «Федеральный исследовательский центр ”Красноярский научный центр Сибирского отделения Российской академии наук”» (ФИЦ КНЦ СО РАН), обособленное подразделение «Научно-исследовательский институт медицинских проблем Севера» (НИИ МПС), Красноярск, Россия
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V.V. Tsukanov, O.V. Smirnova, E.V. Kasparov, A.A. Sinyakov, A.V. Vasyutin, Yu.L. Tonkikh
Krasnoyarsk Science Centre of the Siberian Branch of Russian Academy of Science (FRC KSC SB RAS) separate division “Scientific Research Institute of medical problems of the North” (SRI MPN), Krasnoyarsk, Russia