Amoxicillin secretion by gastric mucosa in Chernobyl nuclear power plant accident recovery workers with atrophic and nonatrophic gastritis undergoing eradication therapy

Relevance. Today gastric cancer is still one of the oncologic diseases most often leading to death. H. pylori eradication reduces risk of gastric cancer, but its efficacy depends on gastric mucosa state. Atrophy of gastric mucosa is more common in Chernobyl nuclear power plant (CNPP) accident recovery workers than in patients who have not been involved in CNPP accident recovery works. It seems especially important to investigate the features of antibiotics transport to H. pylori colonization area in this contingent.

Intention – to determine the features of amoxicillin secretion by gastric mucosa in CNPP accident recovery workers with atrophic and nonatrophic gastritis undergoing H. pylori eradication.

Methodology. 65 CNPP accident recovery workers were divided into groups depending on state of gastric mucosa according to endoscopic and histological examination, immunosorbent assay of pepsinogens I and II and gastrin-17 basal serum levels. On the first day of eradication therapy, gastric secretion samples were obtained via nasogastric probe 30, 60, 120, 180 and 240 minutes after oral amoxicillin administration. Drug concentrations in gastric secretion were assessed via liquid chromatography-mass spectrometry.

Results and discussion. Amoxicillin concentrations in gastric secretion samples were lower (р < 0.01) in patients with atrophic antral gastritis than in patients with normal gastric mucosa and atrophic fundal gastritis. Patients with fundal atrophy were characterized by lower amoxicillin concentrations 30 and 60 (p = 0.02) minutes after drug intake than in patients with normal gastric mucosa, and higher concentration in the 120th (p < 0.01) and 180th (p = 0.02) minute than in patients with antral atrophy. Amoxicillin concentrations in patients with antral atrophy were lower (p < 0.01) than in non-atrophy group in the 30th, 60th and 120th minute. In the 240th minute, amoxicillin concentrations in patients with fundal atrophy exceeded concentrations in both other groups (p < 0.01). Amoxicillin concentration peak was registered in patients with fundal and antral atrophy in the 180th minute, in patients without atrophy – from the 30th to 120th minute.

Conclusion. Atrophy of gastric mucosa is characterized by decreased transport of orally administered amoxicillin from bloodstream to gastric lumen. Depending on gastric mucosa state, amoxicillin concentrations in gastric secretion should be evaluated at different time points after drug administration: in patients with atrophic gastritis – in the 180th minute, in patients without atrophy – in the 120th minute. While predicting the efficacy and choosing H. pylori eradication regimen, morphological and functional state of gastric mucosa should be taken into account.

1. Denisov N.L., Ivashkin V.T., Lobzin Ju.V., Golofeevskii V.Ju. Effektivnost’ eradikatsii Helicobacter pylori v zavisimosti ot urovnya produktsii sekretornogo immunoglobulina A i morfologicheskikh izmenenii slizistoi obolochki zheludka [Efficacy of Helicobacter pylori eradication in relation to the level of secretory immunoglobulin A production and morphological changes of the stomach mucosa]. Rossiiskii zhurnal gastroenterologii, gepatologii, koloproktologii [The Russian Journal of Gastroenter ology, Hepatology, Coloproctology]. 2007. N 3. Pp. 41–45. (In Russ.)

2. Sablina A.O., Aleksanin S.S. Atroficheskii gastrit u likvidatorov posledstvii avarii na Chernobyl’skoi atomnoi elektrostantsii v otdalennom periode [Atrophic gastritis in Chernobyl nuclear power plant accident recovery workers in remote period]. Mediko-biologicheskie i sotsial’no-psikhologicheskie problemy bezopasnosti v chrezvychaynykh situatsiyakh [Medico-Biological and Socio-Psychological Problems of Safety in Emergency Situations]. 2020. N 1. Pp. 36–46. DOI: 10.25016/2541-7487-2020-0-1-36-46. (In Russ.)

3. Correa P. A Human Model of Gastric Carcinogenesis. Cancer Res. 1988. Vol. 48, N 13. Pp. 3554–3560.

4. De Martel C., Georges D., Bray F. [et al.]. Global burden of cancer attributable to infections in 2018: a worldwide incidence. Lancet Glob. Health [Electronic resource]. 2020. Vol. 8, N 2. Pp. 180–190. DOI: 10.1016/S2214-109X(19)30488-7.

5. 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. Vol. 20, N 10. Pp. 1161–1181. DOI: 10.1097/00000478-199610000-00001.

6. Endo H., Yoshida H., Ohmi N. [et al.]. Localization of [14C] amoxicillin in rat gastric tissue when administered with lanzoprazole and clarithromycin. J. Antimicrob. Chemother. 2001. Vol. 48, N 6. Pp. 923–926. DOI 10.1093/jac/48.6.923.

7. Gupta S., Li D., El Serag H.B. [et al.]. AGA Clinical Practice Guidelines on Management of Gastric Intestinal Metaplasia. Gastroenterology. 2020. Vol. 158, N 3. Pp. 693–702. DOI: 10.1053/j.gastro.2019.12.003. 8. Helicobacter pylori Eradication as a Strategy for Preventing Gastric Cancer, IARC Working Group Reports, Vol. 8. International Agency for Research on Cancer, Lyon, France [Electronic resource]. 2014. 190 p. URL: https://publications.iarc.fr/Book-And-Report-Series/Iarc-Working-Group-Reports/-Em-Helicobacter-Pylori-Em-Eradication-As-A-Strategy-For- Preventing-Gastric-Cancer-2014.

8. Kurumado K., Yamakawa T., Ohara T. Changes in Arterioles of the Human Gastric Mucosa With Atrophic Gastritis. Hepatogastroenterology. 1990. Vol. 37, N 2. Pp. 235–238.

9. Malfertheiner P., Megraud F., O’Morain C.A. [et al.]. Management of Helicobacter pylori infection – the Maastricht V/ Florence Consensus Report. Gut. 2016. Vol. 24. Pp. 1–25. DOI 10.1136/gutjnl-2016-312288.

10. Matysiak-Budnik T., Heyman M., Candalh C. [et al.]. In vitro transfer of clarithromycin and amoxicillin across the epithelial barrier: effect of helicobacter pylori. J. Antimicrob. Chemother. 2002. Vol. 50, N 6. Pp. 865–872. DOI: 10.1093/jac/dkf219.

11. McGreevy J.M. Gastric surface cell function: potential difference and mucosal barrier. Am. J. Physiol. 1984. Vol. 247. Pp. 79–87. DOI: 10.1152/ajpgi.1984.247.1.G79.

12. Plummer M., Franceschi S., Vigna J. [et al.]. Global burden of gastric cancer attributable to Helicobacter pylori. Int. J. Cancer. 2014. Vol. 136. N 2. Pp. 487–490. DOI: 10.1002/ijc.28999.

13. Rabassa A.A., Goodgame R., Sutton F.M. [et al.]. Effects of aspirin and Helicobacter pylori on the gastroduodenal mucosal permeability to sucrose. Gut. 1996. Vol. 39, N 2. Pp. 159–163. DOI: 10.1136/gut.39.2.159.

14. Stomach fact sheet. GLOBOCAN 2018, International Agency for Research on Cancer [Electronic resource]. 2019. 2 p. URL: https://gco.iarc.fr/today/fact-sheets-cancers