PATHOGENETIC SUBSTANTIATION OF EUPATILIN PRESCRIPTION IN PATIENTS WITH CHRONIC HELICOBACTER PYLORI-ASSOCIATED GASTRITIS AND CONCOMITANT TYPE 2 DIABETES MELLITUS
About the author:
Radionova Т. О., Skrypnyk I. M., Hopko О. F., Kryvoruchko І. G., Skrypnyk R. I.
CLINICAL AND EXPERIMENTAL MEDICINE
Type of article:
The study of pathogenetic pathways of gastroenterological pathology in patients with type 2 diabetes mellitus (T2DM) and development of differentiated treatment approaches is relevant task of modern medicine. Research aim was to study the state of antioxidant system, resistance of the gastric mucosal barrier, and endogenous toxicity in patients with chronic antral gastritis (CG) and concomitant T2DM considering Helicobacter pylori (HP) status comparing to patients with CG without DM. Research object and methods. 172 patients with endoscopically and histologically confirmed CG were enrolled into the study, 92 out of them had compensated or subcompensated T2DM. According to the HP status all patients were divided onto 4 groups: І (n=71) – had HP(+) CG and T2DM; ІІ (n=21) – had HP(-) CG and T2DM; ІІІ (n=48) – patients with HP(+) CG who had no T2DM; IV (n=32) – those with HP(-) CG who had no T2DM. According to the prescribed treatment patients of the I and III groups were further subdivided: groups І-А (n=35) and ІІІ-А (n=24) underwent standard triple anti-Helicobacter therapy (AHBT); patients in groups І-В (n=36) and ІІI-В (n=24) were additionally prescribed Eupatilin 60 mg (“Stillen”) for 28 days to AHT. In blood serum before the treatment and on the 28 day after the treatment oxidatively modified proteins (OMP), catalase, molecules of the average mass (MAM), free fucose and N-acetylneuraminic acid (NANA) were measured. To objectivize normal ranges, we additionally formed the group of almost healthy (AH) individuals (n=22). Results. The mean age of patients in groups І, ІІ, ІІІ and IV was 62.41±8.95 years, 58.71±8.42 years, 55.88±12.96 years and 51.16±13.62 years respectively. The distribution of male/female in group І was 48/23, group ІІ – 15/6, group ІІІ – 23/25, and group IV – 23/9. At the moment of the first examination the mean value of fasting glucose level in the group I was 7.12±2.12 mmol/L, HbA1c 6.37±0.92%, group ІІ – 7.39±2.65 mmol/L and HbA1c 6.53±0.97%. The presence of concomitant T2DM and НР infection in patients with CG worsens all investigated markers, which highlights the need in therapy intensification in case of comorbidity. Thus, in patients of group I MAM level was 1.1 times more, fucose – 1.6 times more, NANA – 3.6 times more, OMP – 1.3 times more on the background of catalase rise 1.3 times more in comparison to the patients of group IV (p<0,05). The last two readings indicate the inability of antioxidant system to reduce oxidative stress despite of its higher activation. HP infection in patients with CG and concomitant T2DM doesn’t have a significant influence on MAM, catalase and OMP. So probably, these changes in patients of the group I were caused by mechanisms of T2DM. Otherwise, HP infection in patients with T2DM leads to NANA and fucose rise 1.1 times more, which shows the role of HP in disturbances of gastric mucosal barrier. There was a correlation between fucose and NANA levels in patients of the I and II groups with concomitant T2DM (r=+0.305, p=0.01 та r=+0.784, p=0.00003 in patients of groups І and ІІ respectively). Additional Eupatilin prescription to AHT in the group І-В provided intensified positive changes in comparison to I-A group: catalase level was additionally increased 1.2 times more, OMP were decreased 1.2 times less, NANA was decreased 3.2 times less and fucose decreased 1.8 times less (p<0.05). HP eradication was achieved in 83,3% patients who took AHBT with Eupatilin, and in 77,1% who underwent AHT without eupatilin. Thus, additional Eupatilin prescription to the course of AHBT in patients with HP-associated CG and concomitant T2DM allows to normalize the state of gastric mucosal barrier resistance and to improve antioxidant defense of the organism.
type 2 diabetes mellitus, Helicobacter pylori, chronic gastritis, eupatilin.
- Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract [Internet]. 2019;157:107843. Available from: https://doi.org/10.1016/j.diabres.2019.107843
- Asgharnezhad M, Joukar F, Fathalipour M, Khosousi M, Hassanipour S, Pourshams A, et al. Gastrointestinal symptoms in patients with diabetes mellitus and non-diabetic: A cross-sectional study in north of Iran. Diabetes Metab Syndr Clin Res Rev [Internet]. 2019;13(3):2236– 40. Available from: https://doi.org/10.1016/j.dsx.2019.05.028
- Maisey A. A Practical Approach to Gastrointestinal Complications of Diabetes. Diabetes Ther. 2016;7(3):379–86.
- Chedid V, Brandler J, Vijayvargiya P, Park SY, Szarka LA, Camilleri M. Characterization of Upper Gastrointestinal Symptoms, Gastric Motor Functions, and Associations in Patients with Diabetes at a Referral Center. Am J Gastroenterol [Internet]. 2019;114(1):143–54. Available from: http://dx.doi.org/10.1038/s41395-018-0234-1
- Ghadiri-Anari A, Gholami S, Sheyda E, Kharazmi S, Namiranian N. Does diabetic microvascular complications affect gastrointestinal symptoms? Acta Med Iran. 2019;57(3):156–9.
- Avalos DJ, Sarosiek I, Loganathan P, McCallum RW. Diabetic gastroparesis: Current challenges and future prospects. Clin Exp Gastroenterol. 2018;11:347–63.
- Ward SM. Hyperplasia of Interstitial Cells of Cajal Leads to Rapid Gastric Emptying in Diabetes. Gastroenterology [Internet]. 2017;153(2):350–2. Available from: http://dx.doi.org/10.1053/j.gastro.2017.06.039
- Min YW, Ko EJ, Lee JY, Rhee PL. Impaired neural pathway in gastric muscles of patients with diabetes. Sci Rep [Internet]. 2018;8(1):1–9. Available from: http://dx.doi.org/10.1038/s41598-018-24147-y
- Huang Y, Sun J, Wang X, Tao X, Wang H, Tan W. Asymptomatic chronic gastritis decreases metformin tolerance in patients with type 2 diabetes. J Clin Pharm Ther. 2015;40(4):461–5.
- Wan Z, Song L, Hu L, Hu M, Lei X, Huang Y, et al. Helicobacter pylori infection is associated with diabetes among Chinese adults. J Diabetes Investig. 2020;11(1):199–205.
- Zafar K, Ram V, Kumar M. A study of Helicobacter pylori infection in diabetes mellitus. Int J Res Med Sci. 2016;4(9):4166–71.
- Li JZ, Li JY, Wu TF, Xu JH, Huang CZ, Cheng D, et al. Helicobacter pylori infection is associated with type 2 diabetes, not type 1 diabetes: An updated meta-analysis. Gastroenterol Res Pract. 2017;2017. Available from: https://doi.org/10.1155/2017/5715403
- Wang F, Liu J, Lv Z. Association of Helicobacter pylori infection with diabetes mellitus and diabetic nephropathy: A meta-analysis of 39 studies involving more than 20,000 participants. Scand J Infect Dis. 2013;45(12):930–8.
- Yang YJ, Wu CT, Ou HY, Lin CH, Cheng HC, Chang WL, et al. Male non-insulin users with type 2 diabetes mellitus are predisposed to gastric corpus-predominant inflammation after H. pylori infection. J Biomed Sci [Internet]. 2017;24(1):1–8. Available from: https://doi. org/10.1186/s12929-017-0389-x
- Cheng KP, Yang YJ, Hung HC, Lin CH, Wu CT, Hung MH, et al. Helicobacter pylori eradication improves glycemic control in type 2 diabetes patients with asymptomatic active Helicobacter pylori infection. J Diabetes Investig. 2019;10(4):1092–101.
- Malfertheiner P, Megraud F, O’Morain C, Gisbert JP, Kuipers EJ, Axon A, et al. Management of helicobacter pylori infection-the Maastricht V/Florence consensus report. Gut. 2017;66(1):6–30.
- Yao CC, Kuo CM, Hsu CN, Yang SC, Wu CK, Ta WC, et al. First-line helicobacter pylori eradication rates are significantly lower in patients with than those without type 2 diabetes mellitus. Infect Drug Resist. 2019;12:1425–31.
- Bang CS, Baik GH. Attempts to enhance the eradication rate of Helicobacter pylori infection. World J Gastroenterol. 2014;20(18):5252–62.
- Ko SH, Yoo DY, Kim YJ, Choi SM, Kang KK, Kim H, et al. A mechanism for the action of the compound DA-6034 on NF-κB pathway activation in helicobacter pylori-infected gastric epithelial cells. Scand J Immunol. 2011;74(3):253–63.
- Kim J Il, Park SW, Lim JJ, Sohn S Il, Shin JS, Park SC, et al. Gastroprotective effects of the isopropanol extract of Artemisia princeps and its gastroretentive floating tablets on gastric mucosal injury. Acta Pharm. 2017;67(4):479–94.
- Choi YJ, Lee DH, Choi MG, Lee SJ, Kim SK, Song GA, et al. Evaluation of the efficacy and safety of DA-9601 versus its new formulation, DA-5204, in patients with gastritis: Phase III, randomized, double-blind, non-inferiority study. J Korean Med Sci. 2017;32(11):1807–13.
- Kim M, Min YS, Sohn UD. Cytoprotective effect of eupatilin against indomethacin-induced damage in feline esophageal epithelial cells: relevance of HSP27 and HSP70. Arch Pharm Res [Internet]. 2018;41(10):1019–31. Available from: https://doi.org/10.1007/s12272-018- 1066-7
- Lee S, Lee M, Kim SH. Eupatilin inhibits H2O2-induced apoptotic cell death through inhibition of mitogen-activated protein kinases and nuclear factor-κB. Food Chem Toxicol. 2008;46(8):2865–70.
- Ryoo SB, Oh HK, Yu SA, Moon SH, Choe EK, Oh TY, et al. The effects of eupatilin (stillen®) on motility of human lower gastrointestinal tracts. Korean J Physiol Pharmacol. 2014;18(5):383–90.
- Cai M, Phan PTT, Hong JG, Kim DH, Kim JM, Park SJ, et al. The neuroprotective effect of eupatilin against ischemia/reperfusion- induced delayed neuronal damage in mice. Eur J Pharmacol [Internet]. 2012;689(1–3):104–10. Available from: http://dx.doi.org/10.1016/j. ejphar.2012.05.042
- Sapkota A, Gaire BP, Cho KS, Jeon SJ, Kwon OW, Jang DS, et al. Eupatilin exerts neuroprotective effects in mice with transient focal cerebral ischemia by reducing microglial activation. PLoS One [Internet]. 2017;12(2):1–17. Available from: doi:10.1371/journal.pone.0171479
- Shah SWA, Ghias M, Shoaib M, Ali N, Shah I, Umar MN, et al. Antidiabetic potential of flavonoids from Artemisia macrocephalla Jaquem in streptozotocin-induced diabetic rats: Pharmacological and biochemical approach. Pak J Pharm Sci. 2019;32(6):2865–71.
- Maslova HS. Osoblyvosti otsinky chynnykiv ryzyku vynyknennia erozyvno-vyrazkovykh urazhen’ hastroduodenalnoi zony u khvorykh na khronichni leikemii. Suchasna hastroenterolohiia. 2015;5(85):21–5. [in Ukrainian].
- Skrypnik IN. Sovremennye podhody k vyboru antihelikobakternoj terapii u bol’nyh s pepticheskoj jazvoj, associirovannoj s Helicobacter pylori, i ocenka ee vlijanija na sostojanie metabolicheskih processov v slizistom bar’ere gastroduodenal’noj zony. Ukrainskyi terapevtychnyi zhurnal. 2001;3(3):24–33. [in Russian].
Publication of the article:
«Bulletin of problems biology and medicine» Issue 2 (156), 2020 year, 149-154 pages, index UDK 615.322:616.33-002.2:579.84-06:616.379-008.64-03