Koshurba I. Antiulcer and hepatoprotective effects of cryopreserved placenta extract (experimental study)

The dissertation is dedicated to the experimental substantiation of new solutions to the scientific problem concerning the impact of placenta cryoextract (PCE) on the course of peptic ulcer disease (PUD) and liver damage under preventive, therapeutic-preventive, and therapeutic regimens of administration. The study was conducted on 364 non-linear laboratory rats of both sexes under the conditions of Yuriy Fedkovych Chernivtsi National University of the Ministry of Education and Science of Ukraine and the Institute of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine. The aim of the work is to determine the effect of PCE on the course of gastric ulceration and toxic liver damage. Object of study – the progression of pathological changes in the gastric mucosa (GM) and liver in rats under experimental gastric ulceration and liver parenchyma injury. Subject of study – biological properties of PCE and triple anti-ulcer therapy drugs. The anti-ulcer activity (AUA) of PCE was studied using models of ulcerogenesis in the stomach induced by an alcohol-prednisolone mixture (APM), stress, serotonin, and acetic acid. The condition of the GM was assessed using macroscopic, pathomorphological, and biochemical methods. The research results showed that the preventive administration of PCE in the APM-induced ulcerogenesis model reduced the ulcer index (UI) by 7.4 times, corresponding to an AUA of 86.5%. Under the therapeutic regimen, the AUA was 22.2%. The therapeutic-preventive application of PCE reduced the UI by 92.3%, compared to the activity of esomeprazole (97.4%). In the serotonin-induced ulcerogenesis model, the therapeutic-preventive administration of PCE reduced the UI by 13.7 times (anti-ulcerogenic activity 92.6%). In the stress-induced gastric ulcer model, PCE reduced the UI by 9.8 times, corresponding to an AUA of 89.7%. Preventive use of PCE led to an increase in the energy charge of the GM by 35.1% (p<0.001), an increase in the antioxidant-prooxidant index (API) by 3.1 times (p<0.001), a rise in the total protein level by 29.0% (p<0.01), a decrease in the content of oxidized-modified proteins by 20.6% (p<0.01), and an increase in phospholipid levels by 2.3 times (p<0.001) in GM homogenates. Under the therapeutic regimen, the AUA of PCE in the acetic acid-induced ulcerogenesis model was 30.2%. The introduction of PCE after gastric cryodenervation reduced the total acidity by 24.2% (p<0.001) and free acidity by 48.7% (p<0.001), while the ratio of "free/total acidity" decreased by 2 times (p<0.001). The hepatotropic effect of PCE was studied on models of tetrachloromethane (TCM)-induced, D-galactosamine (DGA)-induced, and paracetamol-induced liver damage in rats. According to biochemical studies, it was found that PCE exerts an anticholestatic and energy-stabilizing effect in acute liver injury. The use of PCE in the context of TCM-induced hepatitis resulted in a reduction of reactants with 2-thiobarbituric acid by 35.6% (p<0.01), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels by 56.0% (p<0.001) and 48.6% (p<0.001), respectively. The therapeutic-preventive administration of PCE in DGA-induced hepatitis reduced the levels of thiobarbituric acid reactants by 43.8% (p<0.001), ALT by 2.4 times (p<0.001), AST by 45.3% (p<0.001), and total bilirubin by 53.5% (p<0.001). In paracetamol-induced hepatitis, PCE reduced ALT and AST activities by 44.0% (p<0.001) and 29.6% (p<0.001), respectively, and decreased the level of direct bilirubin by 52.5% (p<0.001) in serum. The hepatoprotective activity of PCE was also studied in models of chronic ethanol-tetrachloromethane-induced (ETCM) liver injury. Combined administration of PCE and triple therapy (esomeprazole, clarithromycin, metronidazole) in the context of chronic ETCM liver damage reduced ALT and AST activities by 30.0% (p<0.05) and 49.2% (p<0.05), respectively, and reduced total bilirubin concentration by 41.7% (p<0.01). Gender differences were observed in the combined administration of PCE and triple therapy drugs. In males, the level of bilirubin decreased by 43.1% (p<0.001), while in females, it decreased by 27.4%. In females after ovariectomy, who were administered PCE, the activity of γ-glutamyltransferase was lower by 45.8% (p<0.01). The scientific novelty of the obtained results lies in the first study of the mechanisms of PCE's anti-ulcer activity under different regimens in ulcerogenesis models. For the first time, the effects of combined administration of PCE and triple therapy drugs on chronic ETCM liver damage were studied, as well as the role of sex factors in the mechanisms of gastric and hepatoprotective activity of PCE. The practical significance of the results lies in the possibility of applying the obtained data to develop new anti-ulcer and hepatoprotective agents, particularly in gastroenterology and hepatology.