Next Article in Journal
Plasma microRNAs as a Potential Biomarker for Identification of Progressive Supranuclear Palsy
Next Article in Special Issue
Artificial Intelligence for Upper Gastrointestinal Endoscopy: A Roadmap from Technology Development to Clinical Practice
Previous Article in Journal
The Use of 18F-FET-PET-MRI in Neuro-Oncology: The Best of Both Worlds—A Narrative Review
Previous Article in Special Issue
Introducing the Sanguis-Filum for Detection of Gastric Mucosal Lesions Prior to Endoscopy: A Study Protocol
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Dynamics of Oxidative Stress in Helicobacter pylori-Positive Patients with Atrophic Body Gastritis and Various Stages of Gastric Cancer

Scientific Research Institute of Medical Problems of the North, Federal Research Centre “Krasnoyarsk Science Centre” of the Siberian Branch of Russian Academy of Science, 660022 Krasnoyarsk, Russia
*
Author to whom correspondence should be addressed.
Diagnostics 2022, 12(5), 1203; https://doi.org/10.3390/diagnostics12051203
Submission received: 28 March 2022 / Revised: 5 May 2022 / Accepted: 6 May 2022 / Published: 11 May 2022
(This article belongs to the Special Issue Advances in the Detection and Screening of Gastric Cancer)

Abstract

:
Gastric cancer is a global health problem. The pathogenesis of this disease remains unclear. This study included 198 H. pylori (+) men aged 45 to 60 years old. Group A included 63 practically healthy men, group B included 45 men with severe atrophic body gastritis, group C included 37 men with epithelial gastric cancer stages I–II according to TNM, and group D included 54 men with epithelial gastric cancer stages III–IV according to the TNM scale. The content of malondialdehyde (MDA), diene conjugates (DCs), superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and glutathione peroxidase (GPO) was detected using an enzyme immunoassay (ELISA) or spectrophotometric methods in the blood plasma. The concentrations of MDA and DC were increased in the patients of group B compared with group A, and in patients of groups C and D compared with groups A and B. The ratio of MDA/SOD and MDA/CAT was decreased in the patients in group D compared with the patients in group C, and was significantly higher compared with group A. The ratios of MDA/GPO and MDA/GST increased linearly and were at a maximum in groups C and D. Our work determined that indicators of oxidative stress may be the biochemical substrate, which brings together the various stages of the Correa cascade, and may explain disease progression. The dynamics of changes in the content of SOD and CAT in the plasma in patients with gastric cancer may be a target of future investigations.

1. Introduction

In 2018, more than 1 million new cases of gastric cancer (GC) were detected worldwide and 782,683 deaths from this disease were registered [1]. The global age-standardized incidence of gastric cancer is 11.1 per 100,000 people, and the mortality rate is 8.2 per 100,000 people [2]. In Russia, the incidence of gastric cancer is high and varies in different regions, and is around 20–25 per 100,000 population [3]. The leading paradigm for the pathogenesis of gastric cancer is the Correa cascade, which postulates that Helicobacter pylori (H. pylori) infection causes the development of gastritis, which, under certain conditions, transforms into atrophy, metaplasia, dysplasia, and gastric adenocarcinoma [4,5]. Regarding this, in 2019–2021, European [6], British [7], and American [8,9] recommendations for the management of patients with precancerous changes in the stomach were published.
Currently, there are a number of works confirming the significance of oxidative stress regarding the development of gastritis and gastric cancer [10,11,12]. H. pylori disrupts intracellular processes in the epithelium, causing inflammation and epigenetic modifications [13,14]. Regarding inflammation, the response of the host organism is accompanied by the involvement of immune cells through their release of cytokines with the possible formation of reactive oxygen species (ROS), which leads to oxidative stress and contributes to deoxyribonucleic acid (DNA) damage and carcinogenesis [15]. In H. pylori-infected cells, processes that prevent the activation of the immune and antioxidant systems of the host organism occur [16]. Modern works have emphasized the prospects of studying oxidative stress indicators, the results of which may influence the development of new approaches for the prevention of gastric cancer [17,18,19].

Aim of Research

The aim of this research was to study the indicators of lipid peroxidation and antioxidant enzymes in the blood plasma of H. pylori-positive men with atrophic gastritis and gastric cancer.

2. Materials and Methods

We examined 198 H. pylori-positive male patients aged 45 to 60 years old, among which 63 were practically healthy men (group A), 45 were patients with atrophic body gastritis (group B), 37 were patients with epithelial gastric cancer stages I–II according to the international TNM classification (group C), and 53 were patients with epithelial gastric cancer stages III–IV according to the international TNM classification (group D).
Group A included 63 men with a mean age of 48.7 ± 3.9 years old, without gastroenterological complaints and gastroenterological anamnesis. The recruitment of patients was carried out from persons who underwent a planned medical examination at the Research Institute of Medical Problems of the North, FRC KSC SB RAS. During medical monitoring, patients underwent clinical and biochemical blood tests; X-ray diagnostics; electrocardiography; and routine consultations with a cardiologist, and, if indicated, other specialists. Patients were included in group A only in the absence of severe chronic diseases of various organs and systems. To exclude atrophic body gastritis, the content of pepsinogen-1 and pepsinogen-2 was determined using an enzyme immunoassay using an ELISA analyzer “MULTISKAN FC” (Thermo Fisher Scientific, Waltham, MA, USA) using the test system “Gastropanel” (Biohit, Helsinki, Finland). The exclusion criteria for atrophic body gastritis were the content of pepsinogen-1 in the blood serum being more than 50 µg/L and the ratio of pepsinogen-1/pepsinogen-2 being more than 3.
Group B had 45 male patients (mean age 51.2 ± 4.9 years old) with chronic atrophic body gastritis (CAG). For the diagnosis of atrophic body gastritis, a morphological study of the biopsy specimens from three sections of the stomach obtained during fibroesophagogastroduodenoscopy (FEGDS) was used in accordance with the modified Sydney classification [20]. Group B included only patients with severe atrophic body gastritis.
Group C included 37 patients with stages I–II epithelial gastric cancer (mean age 51.2 ± 4.9 years) according to the international TNM classification. Group D included 53 patients with stages III–IV epithelial gastric cancer (mean age 53.2 ± 4.9 years old) according to the international TNM classification [21]. The diagnosis of gastric cancer was established by examining patients in the Krasnoyarsk Regional Oncological Dispensary on the basis of comprehensive clinical and instrumental examination, which included mandatory histological diagnostics.
In all of the examined groups, the determination of H. pylori was performed using a 13C-urease breath test using the Iris Doc apparatus. Only H. pylori-positive patients were included in the study.
The study material was venous blood, which was taken from patients in the morning, after a 12 h fast, from the cubital vein into Vacutainer tubes with sodium heparin solution (5 IU/mL). The blood plasma was isolated by centrifugation and was frozen at −80 °C for the biochemical analyses.
The concentrations of malonic dialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and glutathione peroxidase (GPO) were measured using the enzyme immunoassay method (ELISA) on Thermo Scientific Multiskan FC (Thermo Fisher Scientific, Waltham, MA, USA) apparatus using a human ELISA kit (SunRed Biotechnology Company, Shanghai, China) based on sandwich-linked ELISA using two specific and high affinity monoclonal antibodies. The concentration of studied substances was measured in ng/mL.
The ratios of MDA/SOD, MDA/CAT, MDA/GPO, and MDA/GST were calculated.
The content of conjugated diene structures (DCs) of lipid hydroperoxides was determined by spectrophotometry on a GENESYS 10S UV–VIS (Thermo Fisher Scientific, USA) apparatus, with measurements at a wavelength of 232 nm. The DC content was measured in µmol/L [22].
The study was conducted with permission from the Ethics Committee of the Scientific Research Institute of Medical Problems of the North, FRC KSC SB RAS (protocol no. 11 dated 11 November 2013). For working with the examined patients, the ethical principles required by the Russian Federation Constitution and the Declaration of Helsinki from the World Medical Association were met. All participants were informed of the purpose and procedure of the study and were asked to provide written informed consent to the study confirming their voluntary participation in the study.

Statistical Analysis

Statistical data processing was carried out using the Statistica 7.0 software package (StatSoft, Tulsa, OK, USA). The analysis of the conformity of the type of distribution of the sign to the law of normal distribution was carried out using the Shapiro–Wilk test. The median (Me) and interquartile range of percentiles (C25–C75) were calculated when describing the sample. The significance of differences between the indicators of independent samples was assessed using the Mann–Whitney U test for pairwise comparison of groups and the Kruskal–Wallis H test to compare multiple groups (p < 0.05).

3. Results

We analyzed the gender, age, anthropometric, anamnestic characteristics, and laboratory parameters of the examined patients. Patients were gender identical (only males were examined) and practically did not differ in age. A decrease in body weight and an increase in the content of white blood cells in the blood were found in both groups of patients with gastric cancer in comparison with healthy individuals and persons with atrophic gastritis. Hemoglobin and erythrocytes decreased, and the neutrophil-to-lymphocyte ratio increased in patients with stages III–IV gastric cancer compared with healthy individuals and persons with atrophic gastritis. With the increase in stage of gastric cancer, the frequency of tobacco smoking increased and the frequency of alcohol consumption decreased (Table 1).
The content of lipid peroxidation products in the blood plasma was significantly increased in patients with gastric cancer in comparison with the control group, which consisted of practically healthy individuals, and with the atrophic gastritis group. For example, the level of MDA in the plasma of patients with stages III–IV gastric cancer was 72.7 times higher, and DC was 7.7 times higher in comparison with group A. It is noteworthy that in patients with severe atrophic body gastritis, a significant increase in both the primary and end products of blood lipid peroxidation was also determined in comparison with group A (Figure 1 and Figure 2).
The significance of differences was assessed by the Kruskal–Wallis H test and Mann–Whitney U test. Kruskal–Wallis H test: p < 0.001.
Mann–Whitney U test: p1–2 = 0.03; p2–3 = 0.03; p3–4 = 0.02.
The significance of differences was assessed using the Kruskal–Wallis H test and Mann–Whitney U test. Kruskal–Wallis H test: p < 0.001.
Mann–Whitney U test: p1–2 = 0.02; p2–3 = 0.001; p3–4 = 0.02.
All of the indicators of antioxidant protection we studied could be divided into the following two units: the main bifunctional system (SOD and CAT) and the glutathione link (GST and GPO). In patients with CAG and GC stages I–II, unidirectional increases in the concentration of superoxide dismutase and catalase enzymes relative to the control were detected. In patients with gastric cancer stages III–IV, differences were found in the form of a slight increase in the concentration of SOD and a severe increase in the content of CAT (Table 2). Enzymes of the glutathione link also showed their activity in different ways in the groups; there was an increase in the content of GST and GPO in patients with CAG and GC stages I–II, and an unbalanced activity in patients with GC stages III–IV in the form of a significant decrease in GST, and a slight increase in the concentration of GPO.
To assess the dynamics of the relationship between lipid peroxidation and antioxidant protection factors, we studied the relationship of MDA and the studied antioxidant enzymes. The patterns obtained were not unidirectional. The ratio of MDA/SOD and MDA/CAT clearly decreased in the patients in group D compared with the patients in group C, and were significantly higher in comparison with group A. This indicated that in patients with stages III–IV gastric cancer, the dynamics of an increase in SOD and CAT in the plasma was higher in comparison with the change in the concentration of MDA than in patients with stages I–II gastric cancer (Figure 3).
The ratios of MDA/GPO and MDA/GST had simpler and more obvious linear characteristics. The MDA/GST ratio was significantly increased in group D compared with groups A, B, and C. Significant differences in the MDA/GPO ratio were recorded when comparing group D with group A and group B (Figure 4).

4. Discussion

Oxidative stress is one of the significant aspects of the pathogenesis of diabetes, atherosclerosis, neurodegenerative diseases, and cancer of various localizations [23,24,25]. Reactive oxygen species (ROS), which include superoxide (•O2), hydrogen peroxide (H2O2), and singlet oxygen and hydroxyl radical (•OH), are generally considered to be strong oxidizing agents and can accumulate in the organism when exposed to ultraviolet radiation, radiation exposure, over nutrition, and tobacco smoking [26]. The accumulation of ROS leads to the oxidation of biological macromolecules, which include proteins, lipids, and nucleic acids, causing their structural and functional changes. The oxidation of fatty acids leads to the formation of aldehydes. Currently, the most studied fatty acid is MDA [27]. MDA plays an essential role in cellular processes and can promote DNA changes, which is one of the stages of carcinogenesis [28,29,30].
The organism has a mechanism to protect it from oxidative stress and lipid peroxidation products. The main enzymatic antioxidants are superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPO), and glutathione S-transferase (GST). SOD catalyzes the dismutation of superoxide into oxygen and hydrogen peroxide. There are works that show that a decrease in the activity of SOD in the intestine causes stomach ulcers, and an increase in the activity of SOD is associated with the healing of ulcerative defects [31].
It has been shown that in the tissues of adenocarcinoma of the stomach and squamous cell carcinomas of the esophagus, there is an increased expression of manganese SOD compared with the normal mucosa [32]. Regarding the issue of changes in SOD activity during carcinogenesis, there is no single point of view. Thus, a decrease in SOD activity in the tumor tissue compared with healthy tissue has been observed in non-small-cell lung cancer [33], bladder cancer [34], and ovarian cancer [35]. An increase in the activity of this enzyme has been reported in colorectal cancer in tumor tissue [36] and blood serum [37].
CAT is a cellular enzyme that dismutates H2O2 into H2O and O2 [38]. H. pylori is capable of synthesizing CAT for deactivate H2O2 and surviving in the host organism [39]. A decrease in the activity of CAT has been recorded in patients with gastric adenocarcinoma [40].
GPO converts glutathione (GSH) to its oxidized form (GS-SG), and during this process, reduces H2O2 to H2O. It has been argued that GPO provides the first line of defense against reactive oxygen species in the gut [41]. GST belongs to the family of metabolic isoenzymes and has the ability to catalyze the conjugation of GSH with xenobiotic substrates for the purpose of detoxification [42,43].
A number of studies have been devoted to the role of oxidative stress and H. pylori in the pathogenesis of gastric cancer [17,29,44,45]. H. pylori virulence factors activate the signaling pathways of oxidative stress and are mediators of chronic inflammation in host cells. H. pylori is able to block the antibacterial effect of neutrophils and induce DNA methylation, which stimulates cell proliferation towards poorly differentiated gastric cells [12]. H. pylori strains containing CagA and VacA are characterized by an increased survival and adhesion ability, which increases damage to gastric epithelial cells and makes it possible to evade the immune response of the macro-organism [46]. It is known that CagA strains, as a result of the expression of spermine oxidase (SMO), induce higher levels of hydrogen peroxide (H2O2) production, which activate caspase-mediated epitheliocyte apoptosis and oxidative DNA damage [47,48]. CagA positivity is largely associated with an increased expression of tumor necrosis factor α (TNFα) and interleukin (IL)-8, both of which are markers of inflammation and oxidative stress [49]. Vacuolating cytotoxin A (VacA) induces Ca2+ influx, production of reactive oxygen species (ROS), activation of the nuclear factor kappa light chain enhancer of B cell activation (NFκB), and increased expression of chemokines, presumably increasing the influx of pro-inflammatory immune system cells to the site of bacterial infection of H. pylori [50].
Vacuolating cytotoxin A (VacA) induces Ca2+ influx, the production of reactive oxygen species (ROS), activation of the nuclear factor of kappa light chain enhancer of B cell activation (NFκB), and increased expression of chemokines, presumably increasing the influx of pro-inflammatory cells of the immune system to the site of H. pylori infection [50]. Intracellular Ca2+ and ROS of granulocytes further lead to oxidative stress [51,52]. VacA disrupts autophagy in human gastric epithelial cells and increases cellular ROS, which initiate the creation of an environment conducive to oxidative DNA damage with subsequent neoplastic transformations and cancer development [53,54].
An additional virulence factor of H. pylori, γ-glutamyltransferase (GGT), induces the production of H2O2 in gastric epithelial cells, and increases NFκB activation and the production of IL-8, a cytokine with pro-oncogenic properties [55,56,57]. Urease and neutrophil-activating protein A (NapA) are two virulence factors of H. pylori that promote neutrophil infiltration and ROS production [58]. Infiltrating neutrophils are characterized by increased resistance to apoptosis, have an extended lifespan, and are potential factors contributing to chronic inflammation caused by H. pylori infection [58,59,60]. NapA also has the function of attracting neutrophils to the site of infection and induces a respiratory burst of infiltrating neutrophils, which contributes to cellular oxidative stress and DNA damage. Hypothetically, neutrophil ROS should nonspecifically kill both infected and uninfected cells, as well as the pathogen. In addition, NapA protects H. pylori from the release of oxyradicals, maintaining the cycle of neutrophil infiltration and oxidative burst [61,62]. In macrophages, H. pylori also increases SMO expression and H2O2 release, which induces apoptosis in these cells [48].
Our results indicating a significant increase in lipid peroxidation in patients with stomach cancer are consistent with previously expressed views. We did not find information in the available literature that would allow us to clearly interpret the heterogeneous changes in antioxidant enzymes in patients with stages III–IV stomach cancer. One of the possible explanations for the severe increase in CAT in the blood of patients with stages III–IV stomach cancer may be that CAT belongs to intracellular enzymes, and metastatic stages of cancer are accompanied by massive cell cytolysis and the release of enzymes into the extracellular space.

5. Conclusions

This study used four groups of patients—practically healthy individuals, patients with severe atrophic body gastritis, and patients with gastric cancer of various stages according to the TNM classification—and led to several important results. Firstly, oxidative stress plays an important role in the pathogenesis of gastric cancer. Secondly, we demonstrated the presence of oxidative stress in the blood plasma of patients in group B in comparison with the patients in group A. From our point of view, these data confirm the reality of the Correa cascade. At the same time, indicators of oxidative stress can be a biochemical substrate that brings together different stages of the cascade and determines the progress of the disease. Third, another interesting pattern of our work was that we determined a severe increase in the concentrations of SOD and CAT in the blood plasma of patients with stages III–IV gastric cancer. In group D, the intensity of the increase in the content of SOD and CAT in the blood plasma was higher than the increase in the content of MDA. A similar pattern was not observed for glutathione enzymes. We hope that further research will be useful in explaining this phenomenon.

Author Contributions

Conceptualization, V.V.T.; methodology, O.V.S.; clinical examination, E.V.K., J.L.T., and M.A.C.; laboratory investigation, A.A.S.; data curation, A.A.S. and A.V.V.; statistical analysis, A.A.S., A.V.V., and M.A.C.; writing—original draft preparation, O.V.S.; writing—review and editing, V.V.T.; writing—English translation, A.V.V. and J.L.T.; project administration, V.V.T. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki, and was approved by the Institutional Ethics Committee of the Scientific Research Institute of Medical Problems of the North, FRC KSC SB RAS (protocol no. 11, date of approval 11 November 2013).

Informed Consent Statement

Informed consent was obtained from all of the subjects involved in the study.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018, 68, 394–424. [Google Scholar] [CrossRef] [Green Version]
  2. Thrift, A.P.; Nguyen, T.H. Gastric Cancer Epidemiology. Gastrointest. Endosc. Clin. N. Am. 2021, 31, 425–439. [Google Scholar] [CrossRef]
  3. Tsukanov, V.V.; Butorin, N.N.; Maady, A.S.; Shtygasheva, O.V.; Amelchugova, O.S.; Tonkikh, J.L.; Fassan, M.; Rugge, M. Helicobacter pylori Infection, Intestinal Metaplasia, and Gastric Cancer Risk in Eastern Siberia. Helicobacter 2011, 16, 107–112. [Google Scholar] [CrossRef]
  4. Correa, P. Gastric cancer: Overview. Gastroenterol. Clin. N. Am. 2013, 42, 211–217. [Google Scholar] [CrossRef] [Green Version]
  5. Rugge, M.; Savarino, E.; Sbaraglia, M.; Bricca, L.; Malfertheiner, P. Gastritis: The clinico-pathological spectrum. Dig. Liver Dis. 2021, 53, 1237–1246. [Google Scholar] [CrossRef]
  6. Pimentel-Nunes, P.; Libânio, D.; Marcos-Pinto, R.; Areia, M.; Leja, M.; Esposito, G.; Garrido, M.; Kikuste, I.; Megraud, F.; Matysiak-Budnik, T.; et al. Management of epithelial precancerous conditions and lesions in the stomach (MAPS II): European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter and Microbiota Study Group (EHMSG), European Society of Pathology (ESP), and Sociedade Portuguesa de Endoscopia Digestiva (SPED) guideline update 2019. Endoscopy 2019, 51, 365–388. [Google Scholar] [CrossRef] [Green Version]
  7. Banks, M.; Graham, D.; Jansen, M.; Gotoda, T.; Coda, S.; di Pietro, M.; Uedo, N.; Bhandari, P.; Pritchard, D.M.; Kuipers, E.J.; et al. British Society of Gastroenterology guidelines on the diagnosis and management of patients at risk of gastric adenocarcinoma. Gut 2019, 68, 1545–1575. [Google Scholar] [CrossRef] [Green Version]
  8. Gupta, S.; Li, D.; El Serag, H.B.; Davitkov, P.; Altayar, O.; Sultan, S.; Falck-Ytter, Y.; Mustafa, R.A. AGA Clinical Practice Guidelines on Management of Gastric Intestinal Metaplasia. Gastroenterology 2020, 158, 693–702. [Google Scholar] [CrossRef] [Green Version]
  9. Shah, S.C.; Piazuelo, M.B.; Kuipers, E.J.; Li, D. AGA Clinical Practice Update on the Diagnosis and Management of Atrophic Gastritis: Expert Review. Gastroenterology 2021, 161, 1325–1332.e7. [Google Scholar] [CrossRef]
  10. 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, 1532–1540. [Google Scholar] [CrossRef]
  11. Danis, N.; Ozkan, A.E.; Karatas, F.; Cakici, C.; Yigitbasi, T.; Sevencan, N.O.; Kayhan, B. The importance of antioxidant status in gastric intestinal metaplasia. J. Med. Biochem. 2021, 40, 378–383. [Google Scholar] [CrossRef]
  12. Jain, U.; Saxena, K.; Chauhan, N. Helicobacter pylori induced reactive oxygen Species: A new and developing platform for detection. Helicobacter 2021, 26, e12796. [Google Scholar] [CrossRef]
  13. 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, 1702–1707. [Google Scholar] [CrossRef]
  14. Valenzuela, M.A.; Canales, J.; Corvalán, A.H.; Quest, A.F. Helicobacter pylori-induced inflammation and epigenetic changes during gastric carcinogenesis. World J. Gastroenterol. 2015, 21, 12742–12756. [Google Scholar] [CrossRef]
  15. Zhang, R.G.; Duan, G.C.; Fan, Q.T.; Chen, S.Y. Role of Helicobacter pylori infection in pathogenesis of gastric carcinoma. World J. Gastrointest. Pathophysiol. 2016, 7, 97–107. [Google Scholar] [CrossRef]
  16. Buommino, E.; Donnarumma, G.; Manente, L.; De Filippis, A.; Silvestri, F.; Iaquinto, S.; Tufano, M.A.; De Luca, A. The Helicobacter pylori protein HspB interferes with Nrf2/Keap1 pathway altering the antioxidant response of Ags cells. Helicobacter 2012, 17, 417–425. [Google Scholar] [CrossRef]
  17. Han, L.; Shu, X.; Wang, J. Helicobacter pylori-Mediated Oxidative Stress and Gastric Diseases: A Review. Front. Microbiol. 2022, 13, 811258. [Google Scholar] [CrossRef]
  18. Wu, Z.; Wang, L.; Wen, Z.; Yao, J. Integrated analysis identifies oxidative stress genes associated with progression and prognosis in gastric cancer. Sci. Rep. 2021, 11, 3292. [Google Scholar] [CrossRef]
  19. Braga-Neto, M.B.; Costa, D.V.S.; Queiroz, D.M.M.; Maciel, F.S.; de Oliveira, M.S.; Viana-Junior, A.B.; Santos, F.A.; Leitao, R.F.C.; Brito, G.A.C.; Vasconcelos, P.R.L.; et al. Increased Oxidative Stress in Gastric Cancer Patients and Their First-Degree Relatives: A Prospective Study from Northeastern Brazil. Oxid. Med. Cell. Longev. 2021, 2021, 6657434. [Google Scholar] [CrossRef]
  20. Dixon, M.F.; Genta, R.M.; Yardley, J.H.; 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, 1161–1181. [Google Scholar] [CrossRef]
  21. Brierley, J.D.; Gospodarowicz, M.K.; Wittekind, C. TNM Classification of Malignant Tumours, 8th ed.; Wiley Blackwell: Hoboken, NJ, USA, 2017; pp. 63–67. Available online: https://www.wiley.com/en-gb/TNM+Classification+of+Malignant+Tumours%2C+8th+Edition-p-9781119263579 (accessed on 5 May 2022).
  22. Gavrilov, V.B.; Gavrilova, A.R.; Khmara, N.F. Measurement of diene conjugates in blood plasma using the UV absorption of heptane and isopropanol extracts. Lab. Delo 1988, 2, 60–64. Available online: https://pubmed.ncbi.nlm.nih.gov/2452294 (accessed on 5 May 2022). (In Russian).
  23. Ito, F.; Sono, Y.; Ito, T. Measurement and Clinical Significance of Lipid Peroxidation as a Biomarker of Oxidative Stress: Oxidative Stress in Diabetes, Atherosclerosis, and Chronic Inflammation. Antioxidants 2019, 8, 72. [Google Scholar] [CrossRef] [Green Version]
  24. Ho, E.; Galougahi, K.K.; Liu, C.C.; Bhindi, R.; Figtree, G.A. Biological markers of oxidative stress: Applications to cardiovascular research and practice. Redox Biol. 2013, 1, 483–491. [Google Scholar] [CrossRef] [Green Version]
  25. Gentile, F.; Arcaro, A.; Pizzimenti, S.; Daga, M.; Cetrangolo, G.P.; Dianzani, C.; Lepore, A.; Graf, M.; Ames, P.R.J.; Barrera, G. DNA damage by lipid peroxidation products: Implications in cancer, inflammation and autoimmunity. AIMS Genet. 2017, 4, 103–137. [Google Scholar] [CrossRef]
  26. Forman, H.J. Redox signaling: An evolution from free radicals to aging. Free Radic. Biol. Med. 2016, 97, 398–407. [Google Scholar] [CrossRef] [Green Version]
  27. Fritz, K.S.; Petersen, D.R. An overview of the chemistry and biology of reactive aldehydes. Free Radic. Biol. Med. 2013, 59, 85–91. [Google Scholar] [CrossRef] [Green Version]
  28. Tsikas, D. Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples: Analytical and biological challenges. Anal. Biochem. 2017, 524, 13–30. [Google Scholar] [CrossRef]
  29. Ma, Y.; Zhang, L.; Rong, S.; Qu, H.; Zhang, Y.; Chang, D.; Pan, H.; Wang, W. Relation between gastric cancer and protein oxidation, DNA damage, and lipid peroxidation. Oxid. Med. Cell. Longev. 2013, 2013, 543760. [Google Scholar] [CrossRef]
  30. Ayala, A.; Muñoz, M.F.; Argüelles, S. Lipid peroxidation: Production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid. Med. Cell. Longev. 2014, 2014, 360438. [Google Scholar] [CrossRef]
  31. Naito, Y.; Yoshikawa, T.; Ando, T.; Kishi, A.; Ueda, S.; Oyamada, H.; Kondo, M. Changes in superoxide dismutase activity in the gastric mucosa of peptic ulcer patients. J. Clin. Gastroenterol. 1992, 14, S131–S134. [Google Scholar] [CrossRef]
  32. Janssen, A.M.; Bosman, C.B.; van Duijn, W.; Oostendorp-van de Ruit, M.M.; Kubben, F.J.; Griffioen, G.; Lamers, C.B.; van Krieken, J.H.; van de Velde, C.J.; Verspaget, H.W. Superoxide dismutases in gastric and esophageal cancer and the prognostic impact in gastric cancer. Clin. Cancer Res. 2000, 6, 3183–3192. Available online: https://pubmed.ncbi.nlm.nih.gov/10955802 (accessed on 5 May 2022).
  33. Zalewska-Ziob, M.; Adamek, B.; Kasperczyk, J.; Romuk, E.; Hudziec, E.; Chwalińska, E.; Dobija-Kubica, K.; Rogoziński, P.; Bruliński, K. Activity of Antioxidant Enzymes in the Tumor and Adjacent Noncancerous Tissues of Non-Small-Cell Lung Cancer. Oxid. Med. Cell. Longev. 2019, 2019, 2901840. [Google Scholar] [CrossRef] [Green Version]
  34. Islam, M.O.; Bacchetti, T.; Ferretti, G. Alterations of Antioxidant Enzymes and Biomarkers of Nitro-oxidative Stress in Tissues of Bladder Cancer. Oxid. Med. Cell. Longev. 2019, 2019, 2730896. [Google Scholar] [CrossRef] [Green Version]
  35. Ramadan, A.; Hemida, R.; Nowara, A.; Eissa, L.A.; El-Gayar, A.M. Role of oxidative stress in epithelial ovarian cancer in Egyptian patients. J. Exp. Ther. Oncol. 2017, 12, 9–15. Available online: https://pubmed.ncbi.nlm.nih.gov/28472559 (accessed on 5 May 2022).
  36. Zińczuk, J.; Maciejczyk, M.; Zaręba, K.; Pryczynicz, A.; Dymicka-Piekarska, V.; Kamińska, J.; Koper-Lenkiewicz, O.; Matowicka-Karna, J.; Kędra, B.; Zalewska, A.; et al. Pro-Oxidant Enzymes, Redox Balance and Oxidative Damage to Proteins, Lipids and DNA in Colorectal Cancer Tissue. is Oxidative Stress Dependent on Tumour Budding and Inflammatory Infiltration? Cancers 2020, 12, 1636. [Google Scholar] [CrossRef]
  37. Zińczuk, J.; Maciejczyk, M.; Zaręba, K.; Romaniuk, W.; Markowski, A.; Kędra, B.; Zalewska, A.; Pryczynicz, A.; Matowicka-Karna, J.; Guzińska-Ustymowicz, K. Antioxidant Barrier, Redox Status, and Oxidative Damage to Biomolecules in Patients with Colorectal Cancer. Can Malondialdehyde and Catalase Be Markers of Colorectal Cancer Advancement? Biomolecules 2019, 9, 637. [Google Scholar] [CrossRef] [Green Version]
  38. Schrader, M.; Fahimi, H.D. Peroxisomes and oxidative stress. Biochim. Biophys. Acta 2006, 1763, 1755–1766. [Google Scholar] [CrossRef] [Green Version]
  39. Mori, M.; Suzuki, H.; Suzuki, M.; Kai, A.; Miura, S.; Ishii, H. Catalase and superoxide dismutase secreted from Helicobacter pylori. Helicobacter 1997, 2, 100–105. [Google Scholar] [CrossRef]
  40. Monari, M.; Foschi, J.; Calabrese, C.; Liguori, G.; Di Febo, G.; Rizzello, F.; Gionchetti, P.; Trinchero, A.; Serrazanetti, G.P. Implications of antioxidant enzymes in human gastric neoplasms. Int. J. Mol. Med. 2009, 24, 693–700. [Google Scholar] [CrossRef] [Green Version]
  41. Chu, F.F.; Esworthy, R.S.; Doroshow, J.H. Role of Se-dependent glutathione peroxidases in gastrointestinal inflammation and cancer. Free Radic. Biol. Med. 2004, 36, 1481–1495. [Google Scholar] [CrossRef]
  42. Bhattacharyya, A.; Chattopadhyay, R.; Mitra, S.; Crowe, S.E. Oxidative stress: An essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol. Rev. 2014, 94, 329–354. [Google Scholar] [CrossRef] [Green Version]
  43. Udomsinprasert, R.; Pongjaroenkit, S.; Wongsantichon, J.; Oakley, A.J.; Prapanthadara, L.A.; Wilce, M.C.; Ketterman, A.J. Identification, characterization and structure of a new Delta class glutathione transferase isoenzyme. Biochem. J. 2005, 388, 763–771. [Google Scholar] [CrossRef] [Green Version]
  44. Backert, S.; Neddermann, M.; Maubach, G.; Naumann, M. Pathogenesis of Helicobacter pylori infection. Helicobacter 2016, 21, 19–25. [Google Scholar] [CrossRef]
  45. Varbanova, M.; Frauenschläger, K.; Malfertheiner, P. Chronic gastritis—An update. Best. Pract. Res. Clin. Gastroenterol. 2014, 28, 1031–1042. [Google Scholar] [CrossRef]
  46. 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. [Google Scholar] [CrossRef] [Green Version]
  47. Deep, A.; Verma, K.; Swaroop, S.; Kumar, A.; Rungta, S. Novel coronavirus (COVID-19) and its potential G.I. manifestation: A review. J. Fam. Med. Prim. Care 2020, 9, 5474–5479. [Google Scholar] [CrossRef]
  48. Chaturvedi, R.; Cheng, Y.; Asim, M.; Bussière, F.I.; Xu, H.; Gobert, A.P.; Hacker, A.; Casero, R.A., Jr.; Wilson, K.T. Induction of polyamine oxidase 1 by Helicobacter pylori causes macrophage apoptosis by hydrogen peroxide release and mitochondrial membrane depolarization. J. Biol. Chem. 2004, 279, 40161–40173. [Google Scholar] [CrossRef] [Green Version]
  49. Augusto, A.C.; Miguel, F.; Mendonça, S.; Pedrazzoli, J., Jr.; Gurgueira, S.A. Oxidative stress expression status associated to Helicobacter pylori virulence in gastric diseases. Clin. Biochem. 2007, 40, 615–622. [Google Scholar] [CrossRef]
  50. Eruslanov, E.; Kusmartsev, S. Identification of ROS using oxidized DCFDA and flow-cytometry. Methods Mol. Biol. 2010, 594, 57–72. [Google Scholar] [CrossRef]
  51. Kim, J.M.; Kim, J.S.; Lee, J.Y.; Kim, Y.J.; Youn, H.J.; Kim, I.Y.; Chee, Y.J.; Oh, Y.K.; Kim, N.; Jung, H.C.; et al. Vacuolating cytotoxin in Helicobacter pylori water-soluble proteins upregulates chemokine expression in human eosinophils via Ca2+ influx, mitochondrial reactive oxygen intermediates, and NF-kappaB activation. Infect. Immun. 2007, 75, 3373–3381. [Google Scholar] [CrossRef] [Green Version]
  52. Willhite, D.C.; Blanke, S.R. Helicobacter pylori vacuolating cytotoxin enters cells, localizes to the mitochondria, and induces mitochondrial membrane permeability changes correlated to toxin channel activity. Cell. Microbiol. 2004, 6, 143–154. [Google Scholar] [CrossRef]
  53. Raju, D.; Hussey, S.; Ang, M.; Terebiznik, M.R.; Sibony, M.; Galindo-Mata, E.; Gupta, V.; Blanke, S.R.; Delgado, A.; Romero-Gallo, J.; et al. Vacuolating cytotoxin and variants in Atg16L1 that disrupt autophagy promote Helicobacter pylori infection in humans. Gastroenterology 2012, 142, 1160–1171. [Google Scholar] [CrossRef] [Green Version]
  54. Tsugawa, H.; Suzuki, H.; Saya, H.; Hatakeyama, M.; Hirayama, T.; Hirata, K.; Nagano, O.; Matsuzaki, J.; Hibi, T. Reactive oxygen species-induced autophagic degradation of Helicobacter pylori CagA is specifically suppressed in cancer stem-like cells. Cell Host Microbe 2012, 12, 764–777. [Google Scholar] [CrossRef] [Green Version]
  55. Li, M.; Zhang, Y.; Feurino, L.W.; Wang, H.; Fisher, W.E.; Brunicardi, F.C.; Chen, C.; Yao, Q. Interleukin-8 increases vascular endothelial growth factor and neuropilin expression and stimulates ERK activation in human pancreatic cancer. Cancer Sci. 2008, 99, 733–737. [Google Scholar] [CrossRef] [Green Version]
  56. Eftang, L.L.; Esbensen, Y.; Tannæs, T.M.; Bukholm, I.R.; Bukholm, G. Interleukin-8 is the single most up-regulated gene in whole genome profiling of H. pylori exposed gastric epithelial cells. BMC Microbiol. 2012, 12, 9. [Google Scholar] [CrossRef] [Green Version]
  57. Asfaha, S.; Dubeykovskiy, A.N.; Tomita, H.; Yang, X.; Stokes, S.; Shibata, W.; Friedman, R.A.; Ariyama, H.; Dubeykovskaya, Z.A.; Muthupalani, S.; et al. Mice that express human interleukin-8 have increased mobilization of immature myeloid cells, which exacerbates inflammation and accelerates colon carcinogenesis. Gastroenterology 2013, 144, 155–166. [Google Scholar] [CrossRef] [Green Version]
  58. Uberti, A.F.; Olivera-Severo, D.; Wassermann, G.E.; Scopel-Guerra, A.; Moraes, J.A.; Barcellos-de-Souza, P.; Barja-Fidalgo, C.; Carlini, C.R. Pro-inflammatory properties and neutrophil activation by Helicobacter pylori urease. Toxicon 2013, 69, 240–249. [Google Scholar] [CrossRef]
  59. Wilson, K.T.; Crabtree, J.E. Immunology of Helicobacter pylori: Insights into the failure of the immune response and perspectives on vaccine studies. Gastroenterology 2007, 133, 288–308. [Google Scholar] [CrossRef]
  60. Peek, R.M., Jr.; Fiske, C.; Wilson, K.T. Role of innate immunity in Helicobacter pylori-induced gastric malignancy. Physiol. Rev. 2010, 90, 831–858. [Google Scholar] [CrossRef] [Green Version]
  61. Wang, G.; Hong, Y.; Olczak, A.; Maier, S.E.; Maier, R.J. Dual Roles of Helicobacter pylori NapA in inducing and combating oxidative stress. Infect. Immun. 2006, 74, 6839–6846. [Google Scholar] [CrossRef] [Green Version]
  62. Zhao, Y.; Cai, Y.; Chen, Z.; Li, H.; Xu, Z.; Li, W.; Jia, J.; Sun, Y. SpoT-mediated NapA upregulation promotes oxidative stress-induced Helicobacter pylori biofilm formation and confers multidrug resistance. Antimicrob. Agents Chemother. 2021, 65, e00152-21. [Google Scholar] [CrossRef]
Figure 1. The content of diene conjugates in the blood plasma of patients with atrophic gastritis and gastric cancer.
Figure 1. The content of diene conjugates in the blood plasma of patients with atrophic gastritis and gastric cancer.
Diagnostics 12 01203 g001
Figure 2. The content of malonic dialdehyde in the blood plasma of patients with atrophic gastritis and gastric cancer.
Figure 2. The content of malonic dialdehyde in the blood plasma of patients with atrophic gastritis and gastric cancer.
Diagnostics 12 01203 g002
Figure 3. Concentration ratios of malonic dialdehyde to superoxide dismutase and malonic dialdehyde to catalase in the blood plasma of patients with atrophic gastritis and gastric cancer. 1—Group A; 2—Group B; 3—Group C; 4—Group D. The significance of differences was assessed by the Kruskal–Wallis H test and Mann–Whitney U test. Kruskal–Wallis H test: MDA/SOD p < 0.001; MDA/CAT p < 0.001. Mann–Whitney U test MDA/SOD: p1–2 = 0.03, p2–3 < 0.001, p3–4 = 0.02. Mann–Whitney U test MDA/CAT: p1–2 = 0.02, p2–3 < 0.001, p3–4 = 0.02.
Figure 3. Concentration ratios of malonic dialdehyde to superoxide dismutase and malonic dialdehyde to catalase in the blood plasma of patients with atrophic gastritis and gastric cancer. 1—Group A; 2—Group B; 3—Group C; 4—Group D. The significance of differences was assessed by the Kruskal–Wallis H test and Mann–Whitney U test. Kruskal–Wallis H test: MDA/SOD p < 0.001; MDA/CAT p < 0.001. Mann–Whitney U test MDA/SOD: p1–2 = 0.03, p2–3 < 0.001, p3–4 = 0.02. Mann–Whitney U test MDA/CAT: p1–2 = 0.02, p2–3 < 0.001, p3–4 = 0.02.
Diagnostics 12 01203 g003
Figure 4. Concentration ratios of malonic dialdehyde to glutathione peroxidase and malonic dialdehyde to glutathione S-transferase in the blood plasma of patients with atrophic gastritis and gastric cancer. 1—Group A; 2—Group B; 3—Group C; 4—Group D. The significance of differences was assessed using the Mann–Whitney U test. Kruskal–Wallis H test: MDA/GST p < 0.001; MDA/GPO p < 0.001. Mann–Whitney U test MDA/GST: p1–2 = 0.03, p2–3 < 0.001, p3–4 < 0.02; Mann–Whitney U test MDA/GPO: p1–2 = 0.06, p2–3 < 0.001, p3–4 < 0.001.
Figure 4. Concentration ratios of malonic dialdehyde to glutathione peroxidase and malonic dialdehyde to glutathione S-transferase in the blood plasma of patients with atrophic gastritis and gastric cancer. 1—Group A; 2—Group B; 3—Group C; 4—Group D. The significance of differences was assessed using the Mann–Whitney U test. Kruskal–Wallis H test: MDA/GST p < 0.001; MDA/GPO p < 0.001. Mann–Whitney U test MDA/GST: p1–2 = 0.03, p2–3 < 0.001, p3–4 < 0.02; Mann–Whitney U test MDA/GPO: p1–2 = 0.06, p2–3 < 0.001, p3–4 < 0.001.
Diagnostics 12 01203 g004
Table 1. Anthropometric and anamnestic characteristics and laboratory parameters of patients with atrophic gastritis and gastric cancer.
Table 1. Anthropometric and anamnestic characteristics and laboratory parameters of patients with atrophic gastritis and gastric cancer.
Parameter1. Control Group
(n = 63)
p
2. CAG
(n = 45)
p
GC Stages I–II
(n = 37)
p
GC Stages III–IV
(n = 53)
p
Men/Women
n/n
63/045/037/053/0
Age. years
Me (C25–C75)
48.9 (45.6–55.4)51.1 (46.1–56.0)51.4 (46.3–56.4)53.0 (46.9–57.8)
p1–2 = 0.8p1–3 = 0.8p1–4 = 0.6
p2–3 > 0.9p2–4 = 0.8
p3–4 = 0.8
Height, cm
Me (C25–C75)
179 (173–185)178 (172–184)176 (171–182)177 (172–183)
p1–2 = 0.9p1–3 = 0.7p1–4 = 0.8
p2–3 = 0.8p2–4 > 0.9
p3–4 = 0.9
Weight, kg
Me (C25–C75)
83.0 (74.5–91.0)81.0 (72.0–90.5)67.0 (59.5–75.0)61.0 (54.5–68.0)
p1–2 = 0.8p1–3 = 0.003p1–4 < 0.001
p2–3 = 0.008p2–4 < 0.001
p3–4 = 0.1
Tobacco smoking
Abs. (%)
12 (19.0%)13 (28.9%)13 (35.1%)20 (37.7%)
p1–2 = 0.3p1–3 = 0.1p1–4 = 0.04
p2–3 = 0.7p2–4 = 0.5
p3–4 > 0.9
Alcohol consumption
Abs. (%)
23 (36.5%)18 (40.0%)10 (27.0%)10 (18.9%)
p1–2 = 0.8p1–3 = 0.4p1–4 = 0.06
p2–3 = 0.3p2–4 = 0.04
p3–4 = 0.5
Hemoglobin, g/dL
Me (C25–C75)
14.1 (12.4–15.7)13.1 (11.2–14.9)11.7 (9.9–13.6)10.4 (8.7–12.3)
p1–2 = 0.4p1–3 = 0.02p1–4 = 0.005
p2–3 = 0.2p2–4 = 0.03
p3–4 = 0.3
Red blood cells, ×1012/L
Me (C25–C75)
4.7 (4.1–5.2)4.5 (3.8–4.9)4.1 (3.5–4.7)3.7 (3.3–4.2)
p1–2 = 0.6p1–3 = 0.06p1–4 = 0.01
p2–3 = 0.3p2–4 = 0.04
p3–4 = 0.5
White blood cells, ×109/L
Me (C25–C75)
5.6 (4.4–6.9)5.3 (4.1–6.7)9.6 (7.1–11.7)9.9 (7.3–12.1)
p1–2 = 0.8p1–3 = 0.005p1–4 = 0.003
p2–3 = 0.003p2–4 < 0.001
p3–4 = 0.7
Platelet, ×109/L
Me (C25–C75)
271 (216–338)254 (194–319)308 (176–444)298 (165–413)
p1–2 = 0.7p1–3 = 0.2p1–4 = 0.6
p2–3 = 0.1p2–4 = 0.4
p3–4 = 0.8
Neutrophil-to-lymphocyte ratio
Me (C25–C75)
2.21 (1.46–3.02)1.98 (1.24–2.73)2.86 (1.54–4.24)3.15 (1.72–4.58)
p1–2 = 0.8p1–3 = 0.5p1–4 = 0.04
p2–3 = 0.1p2–4 = 0.03
p3–4 = 0.7
Note: the significance of differences in indicators was calculated using the Mann–Whitney U test and χ2.
Table 2. Indicators of antioxidant enzymes in the blood plasma in patients with atrophic gastritis and gastric cancer.
Table 2. Indicators of antioxidant enzymes in the blood plasma in patients with atrophic gastritis and gastric cancer.
Groups
Indicators
1. Control Group (n= 63)
Me (C25–C75)
p
2. CAG (n = 45)
Me (C25–C75)
p
GC Stages I–II (n = 37)
Me (C25–C75)
p
GC Stages III–IV (n = 53)
Me (C25–C75)
p
SOD, ng/mL0.234 (0.225–0.252)0.347 (0.295–0.386)0.489 (0.512–0.605)0.765 (0.754–0.805)
p1–2 = 0.001p1–3 = 0.03p1–4 < 0.001
p2–3 = 0.02p2–4 < 0.001
p3–4 = 0.02
CAT, ng/mL0.472 (0.456–0.489)0.987 (0.972–1.12)1.86 (1.37–2.4)4.52 (3.16–5.1)
p1–2 = 0.03p1–3 = 0.003p1–4 < 0.001
p2–3 = 0.01p2–4 < 0.001
p+ = 0.02
GST, ng/mL241.3 (237.7–262.4)384.2 (375.1–407.3)448.6 (439.3–484.6)217.6 (203.4–229.3)
p1–2 = 0.01p1–3 = 0.01p1–4 = 0.01
p2–3 = 0.002p2–4 = 0.01
p3–4 = 0.02
GPO, ng/mL30.9 (21.4–62.9)58.6 (42.1–76.5)97.4 (78.1–104.4)113.7 (105.2–131.7)
p1–2 = 0.03p1–3 = 0.001p1–4 < 0.001
p2–3 = 0.003p2–4 < 0.001
p3–4 = 0.02
Note: the significance of differences in indicators was calculated using the Mann–Whitney U test.
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Tsukanov, V.V.; Smirnova, O.V.; Kasparov, E.V.; Sinyakov, A.A.; Vasyutin, A.V.; Tonkikh, J.L.; Cherepnin, M.A. Dynamics of Oxidative Stress in Helicobacter pylori-Positive Patients with Atrophic Body Gastritis and Various Stages of Gastric Cancer. Diagnostics 2022, 12, 1203. https://doi.org/10.3390/diagnostics12051203

AMA Style

Tsukanov VV, Smirnova OV, Kasparov EV, Sinyakov AA, Vasyutin AV, Tonkikh JL, Cherepnin MA. Dynamics of Oxidative Stress in Helicobacter pylori-Positive Patients with Atrophic Body Gastritis and Various Stages of Gastric Cancer. Diagnostics. 2022; 12(5):1203. https://doi.org/10.3390/diagnostics12051203

Chicago/Turabian Style

Tsukanov, Vladislav Vladimirovich, Olga Valentinovna Smirnova, Edward Vilyamovich Kasparov, Alexander Alexandrovich Sinyakov, Alexander Viktorovich Vasyutin, Julia Leongardovna Tonkikh, and Mikhail Alexandrovich Cherepnin. 2022. "Dynamics of Oxidative Stress in Helicobacter pylori-Positive Patients with Atrophic Body Gastritis and Various Stages of Gastric Cancer" Diagnostics 12, no. 5: 1203. https://doi.org/10.3390/diagnostics12051203

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop