THE EFFECT OF EUPATILIN ON ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH NSAID-GASTROPATHY WITH CONCOMITANT ISCHEMIC HEART DISEASE

Skrypnyk I. M., Parkhomenko V. V., Gopko O. F., Akimov O. Ye., Iakimishyna L. I.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Mechanisms of non-steroidal anti-inflammatory drugs (NSAIDs)-induced injury of gastric mucosa (GM) include inhibition of cyclooxygenase-1, gastroprotective prostaglandins, increased membrane permeability, activation of proinflammatory mediator products, Helicobacter pylori (H. pylori) infection and endothelial dysfunction. The aim – to study the effect of eupatilin on endothelial dysfunction in patients with NSAID-gastropathy with concomitant ischemic heart disease (IHD). 125 patients with diagnosed stable ischemic heart disease I-II functional class and NSAID-gastropathy were monitored. Depending on the presence of H. pylori, patients were divided into two groups: I (n=82) – NSAIDgastropathy, not associated with H. pylori, II (n=43) – associated with H. pylori. Additional subdivision was done according to the treatment complexes, that were prescribed to patients: I-A (n=44) – received proton pump inhibitors (PPIs) in standard doses and II-A group (n=23) – antihelicobacter therapy (AHBT). Patients of I-B (n = 38) and II-B (n = 20) groups were additionally treated with eupatiline (Stylene) 1 tablet 3 times a day 20-30 minutes before meals during 28 days. H. pylori status was determined in the presence of H. pylori antigen in the stool before treatment and 1-1.5 months after AHBT completion. The edothelial dysfunction was assessed by peroxynitrite concentration and NO-synthases activity (iNOS, еNOS). When determining the activity of NOS in the patient’s blood serum of groups I and II, a significant increase in iNOS activity in 4.4 times and 6.1 times was determined, with simultaneously decreased eNOS activity in 1.5 times and 2.3 times compared with almost healthy (p <0.001), respectively. In the examined patients of groups I and II the peroxynitrite concentration exceeded in 2.4 times and 3.5 times the indicators of almost healthy individuals (р<0.001). In patients during treatment, positive clinical dynamics was observed against the background of basic therapy on average after (5.9±0.6) days, and in patients who were additionally treated with eupatilin – after (4.1±0.3) days (р<0.05). Eradication of H. pylori was achieved in 19 (82.6%) patients of group II-A and in 18 (90%) of group II-B. Final results detailed analysis of group I after 14 days and 1.5 months of observation proved an additional positive effect of eupatilin in the complex treatment of NSAID-gastropathy, which was confirmed by 1.4 times lower (p<0.02) serum iNOS activity, a decreased peroxynitrites concentration in patients of group I-B compared with group I-A in 1.2 times and 1.3 times (p<0.001), respectively. After 14 days of treatment, patients of group II-B compared to patients in group II-A the iNOS activity was significantly lower in 1.17 times (p<0.02) while the eNOS activity was in 1.3 times higher (p<0.03) and peroxynitrite content in 1.4 times lower (p<0.01) in the blood serum. Similar changes were observed after 1.5 months, which was confirmed by significantly lower iNOS activity 1.6 times (p <0.005), peroxynitrite content in 2.0 times (p <0.001) in the serum of patients of group II-B compared with relevant indicators of group II-A. Thus, in patients with NSAID-gastropathy with concomitant ischemic heart disease the signs of endothelial dysfunction were revealed, especially in patients with H. pylori infection. Administration of eupatilin on the background of basic acid-suppressive therapy or AHBT contributed to the normalization of endothelial function by reducing the activity of iNOS, the content of peroxynitrites and increasing of eNOS activity.

NSAID-gastropathy, ischemic heart disease, eupatilin, endothelial dysfunction.

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«Bulletin of problems biology and medicine» Issue 2 (156), 2020 year, 162-166 pages, index UDK 615.322:616.1-092:[616.3-02:615.276-06:616.12-005.4]

10.29254/2077-4214-2020-2-156-162-166