The effect of drugs used in anti - helicobacter therapy on the liver and gut microbiome - an experimental study

Abstract

Study objective: To investigate the adverse effects of antibacterial drugs used for Helicobacter pylori (HP) eradication and included in anti-Helicobacter therapy regimens. The use of various antibacterial drugs led to adverse effects on the hepatobiliary system (manifesting as toxic hepatosis) and the gastrointestinal tract (manifesting as disturbances in the large intestine microbiome) in experimental rats receiving standard anti-Helicobacter therapy. Materials and methods: Experiments were conducted on 20 Wistar rats (males, 4–5 months old, mean body weight 220 g) divided into two groups: Group 1 (control/normal)—intact animals receiving a standard vivarium diet (complete balanced feed); and Group 2 (experimental)—animals receiving a complete diet plus a daily oral mixture of the following drugs for 8 days: omeprazole (Farmak, Kyiv) at 1.3 mg/kg, amoxyl (Kyivmedpreparat, Kyiv) at 50 mg/kg, and clarithromycin (Kyivmedpreparat) at 7.5 mg/kg. Euthanasia was performed on the 12^th day  of the study under thiopental anesthesia (20 mg/kg) via total cardiac exsanguination.

Research results: The leukocyte count and the percentages of neutrophils and lymphocytes were determined in the blood of the experimental animals; additionally, immunodeficiency indices were calculated based on the lymphocyte – to – neutrophil ratio. In the serum of the experimental rats, the following were measured: levels of "liver" markers (alanineaminotransferase and alkaline phosphatase activity); levels of inflammation markers (malon dialdehyde content and elastase activity); and the activity of two protective enzymes—lysozyme (an indicator of nonspecific immunity) and catalase (an antioxidant enzyme). In liver homogenate (50 mg/mLin 0.05 M Tris – HCl buffer), the content of malon dialdehyde and the activity of the following enzymes were determined: elastase, alkalinephosphatase, catalase, lysozyme, and urease (an indicator of microbial load). The antioxidant – prooxidant index was calculated based on the ratio of catalase  activity  to malondialdehyde content, while the degree of dysbiosis was determined according to Levytskyi’s method using the ratio of the relative activities of urease and lysozyme. Statistical analysis of the results was performed according to standard recommendations; data are presented as the mean value (M) and the standard error of the mean (±m). Differences were considered statistically significant at p < 0.05. Conclusions: The use of drugs included in the anti-Helicobacter therapy regimen in an experiment with rats significantly reduced serum lysozyme activity in the test animals, leading to intestinal dysbiosis and a substantial decline in non - specific immunity; concurrently, there was a significant increase in the activity of "liver" markers—alanineaminotransferase and alkaline phosphatase—indicating the development of liver damage in the form of hepatitis and cholestasis.