Relevance. Gastric and duodenal ulcers occur in 6-10% of the adult population, and mortality from peptic ulcers ranges from 5 to 15%. Conservative treatment of this disease almost always involves the use of antisecretory and antibacterial drugs. Existing treatment regimens for peptic ulcer disease, focused on key pathogenetic mechanisms, do not take into account the individual adaptive and trophological characteristics of patients. As a potential antiulcer agent, our attention was drawn to the cryopreserved placenta extract ("Cryocell-cryoextract placenta"). It eliminates the ulcerogenic effect of anti-inflammatory drugs of non-steroidal nature, without affecting their therapeutic efficacy. Objective: to characterize the anti-ulcerogenic effect of therapeutic and prophylactic use of cryopreserved placenta extract in the model of alcohol-prednisolone gastric lesions in rats. Methods. The study was performed on 28 male rats weighing 200-220 g. they were randomized into four groups: I (n = 7) – intact rats, II (n = 7) – control – rats with model pathology (alcohol-prednisolone gastric lesion) without treatment, III (n = 7) – rats with alcohol-prednisolone gastric lesions, which were injected with cryoextract placenta (0.16 ml / kg body weight, intramuscularly), IV (n = 7) – rats with alcohol-prednisolone gastric lesions, which were administered the reference drug esomeprazole, proton pump inhibitor (50 mg / kg , intragastric). Gastric lesions in rats were simulated by intragastric single administration of prednisolone (20 mg/kg) dissolved in 80.0% ethanol (0.6 ml/100 g body weight). Cryoextracts of the placenta were administered intravenously in a prophylactic mode – 1 time per day for 4 days before and 1 time 60 minutes after the introduction of ethanol-prednisolone mixture. In 24 h. after administration of the mixture, rats were removed from the experiment and the size of the stomach (bloating) and the presence of adhesions with adjacent organs were evaluated macroscopically by the following criteria: erosions and hemographies, hyperemia, edema and mucosal fold disorders. For each group, the percentage of experimental animals was calculated according to these characteristics and the average value of their severity. The values of the ulcer index were calculated for each group. Results. The study showed that the introduction of placental cryoexact as well as the reference drug esomeprazole led to a statistically significant (p<0.05) reduction of three times the prevalence of gastric ulcers in rats after administration of alcohol-prednisolone mixture. The use of placental cryoextract in the treatment-and-prophylactic regimen led to a statistically significant (p<0.05) decrease in the value of the ulcer index in 13 times relative to the control rats, and the average score of macroscopic assessment of gastric mucosa was 3.5 times lower and was 1.1±0.24 and 3.9±0.26, respectively. In animals treated with esomeprazole 2 times more moderate (2 [0.5; 3] points) hyperemia of the central nervous system (57.1% and 28.6%, respectively) and several times more moderate (2 [0; 2]). points) edema of the secondary school. In addition, edema of the central nervous system in rats administered esomeprazole led to a clear (3 [2; 3] points) violation of the folding of the central nervous system in 71.4% of rats. In contrast to the use of esomeprazole, placental cryoextract more significantly leveled the hyperemia induced by the introduction of alcohol-prednisolone mixture and edema of the gastric mucosa, which were observed in only 28.6% and 14.3% of rats, respectively. Conclusions. Therapeutic and prophylactic use of placental cryoextract was accompanied by statistically significant (p <0.05) comparable to esomeprazole antiulcer efficacy in the model of ethanol-prednisolone gastric lesion and amounted to 92.3%.
Background. Viral hepatitis is one of the most common and dangerous diseases in the world and is the third most common infectious disease. The development of new, more effective and safer hepatoprotective drugs is an urgent task of biomedicine. A wide range of proven biological properties in cryoextract of human placenta, in particular the presence of antioxidant, immunomodulating and anti-inflammatory effects, suggests that it has a hepatoprotective effect. A model of D-galactosamine toxic hepatitis, which is similar to human viral hepatitis in terms of morphological and biochemical changes in the liver, was chosen for the study. Objective. We are aimed to study the effect of the therapeutic and preventive administration of cryopreserved placenta extract on the metabolic and functional state of the liver in the model of D-galactosamine hepatitis in rats. Methods. The study was conducted on 28 male rats weighing 200–220 g. Hepatitis was simulated by a single intraperitoneal injection of a 20% aqueous solution of D-galactosamine at a dose of 400 mg/kg. The cryoextract was administered in the treatment-prophylactic mode – 1 time per day for 3 days before the administration of D-galactosamine and another 2 days after the administration of the aminosugar (5 administrations in total). Results. The development of experimental D-galactosamine hepatitis in rats leads to the formation of functional and metabolic disorders in the form of the activation of lipid peroxidation processes, a violation of pigment metabolism, a decrease in the protein-synthesizing function and the development of cytolytic syndrome, which were indicated by an increase (p < 0.001) in the level of reactants with thiobarbituric acid in liver homogenates by 2.2 times, an increase (p < 0.001) in the level of total bilirubin by 2.5 times, a decrease (p < 0.001) in the albumin-globulin ratio by 46.8% and an increase (p < 0.001) in the level of alanine-aminotransferases by 2.2 times and the level of aspartate-aminotransferases by 70.3% compared to the values of intact animals. Against the background of the administration of placenta cryoextract in experimental hepatitis, the level of reactants with thiobarbituric acid decreased (p < 0.001) by 43.8%, the level of alanine-aminotransferases decreased (p < 0.001) by 2.4 times, and the level of aspartate-aminotransferases decreased (p < 0.001) by 45.3%; the level of total protein increased (p < 0.01) by 17.4%, and the level of total bilirubin decreased (p < 0.001) by 53.5% compared to the indicators of untreated animals. Conclusions. Administration of cryopreserved placenta extract normalized metabolic processes in the liver and restored its functional state due to antioxidant and membrane-stabilizing effects, which weakened the cytolytic syndrome caused by the administration of D-galactosamine and restored the protein-synthesizing function of the liver. In addition, administration of the specified cryoextract neutralized D-galactosamine-induced hyperbilirubinemia.
Abstract. The search for new strategies for the correction of exogenous toxic liver lesions is due to the steady increase in the incidence of hepatitis and cirrhosis among the working population, which is an important medical and social problem. The aim is to determine the effect of cryopreserved placenta extract (CEP) on the state of the liver of rats with tetrachloromethane (CCl4)-induced damage by indicators of lipid peroxidation (LP) and markers of cytolysis. Materials and methods. Experimental studies were conducted on 28 male rats. Acute CCl4-induced hepatitis was reproduced by a single injection of 50.0% CCl4 oil solution. KEP was administered 1 time per day for 5 days before the introduction of CCl4. The material for the study was whole blood and liver homogenates, in which the content of reactants with thiobarbituric acid (TBA-RP), catalase activity, superoxide dismutase (SOD) activity, alanine aminotransferase (AlAt) and aspartate aminotransferase (AsAt) activity, as well as γ-glutamyl activity were determined. γ-glutamyl transpeptidases (γ-GTP) and alkaline phosphatase (AP) according to standard methods. Results and discussion. The study showed that the content of TBA-RP in liver homogenates was lower (p<0.01) by 35.6% in rats that were prophylactically injected with CEP compared to rats with simulated CCl4-induced hepatitis without treatment (control group). An increase in the level of catalase (p=0.02) with the use of CEP was established by 33.8% and an increase in the activity of SOD (p<0.01) by 45.5% compared to the indicators of rats in the control group. It is also shown that the level of AlAt after administration of CEP decreased (p<0.001) by 56.0%, the level of AsAt decreased (p<0.001) by 48.6%, the level of γ-HTP decreased by 37.8% compared to the rats with untreated CCl4-induced hepatitis. Conclusions. Prophylactic five-day administration of CEP leads to the leveling of CCl4-induced LP activation and signs of cytolysis syndrome.
Background. Peptic ulcer disease has a leading place in the overall structure of digestive diseases: its prevalence is 6.00–10.0 % of the population in developed countries, and mortality ranges from 6 to 9.7 per 100 thousand population. An important etiological factor of this pathology is the neuropsychological background, primarily stress, which under repeated exposure becomes the initiating factor of physiological imbalance between the elements of aggression and protection of the gastric mucosa. The purpose was to establish the mechanisms of the protective activity of placental cryoextract based on the biochemical indicators of lipid peroxidation and antioxidant protection in the gastric mucosa on a model of stress-induced erosive-ulcerative damage. Materials and methods. Studies were performed on 28 nonlinear laboratory male rats weighing 200–220 g. Stress-induced gastric ulcer was modeled under water-immobilization stress in rats according to the K.Y. Takagi et al. In the gastric mucosa, the content of reactants with thiobarbituric acid was determined spectrophotometrically by the method of T. Asakawa et al., catalase activity — spectrophotometrically by the method of M.A. Korolyuk et al., the content of reduced glutathione — spectrophotometrically by the method of E.D. Beutler et al., the level of adenyl nucleotides was determined using chromatographic method. Energy charge was calculated by D.E. Atkinson equation. Results. The prophylactic five-day use of placental cryoextract led to a decrease in the severity of stress-induced lipid peroxidation and energy imbalance in the gastric mucosa. Thus, it was found that rats who received placental cryoextract had a statistically significant (p < 0.001) increase in adenosine triphosphate content by 73.3 %, an increase in adenosine diphosphate (p < 0.001) by 37.3 % and a decrease in adenosine monophosphate (p < 0.001) by 47.6 % that led to an increase in energy charge (p < 0.001) by 35.1 % compared to rats exposed to water-immobilization stress without correction (control group). It was shown that the use of placental cryoextract led to a statistically significant (p < 0.001) increase in the antioxidant-prooxidant index by 3.1 times versus control group, which was (26.60 ± 0.96) and (8.60 ± 0.43), respectively. Conclusions. Prophylactic five-day administration of placental cryoextract leads to the restoration of balance in the system of adenyl nucleotides and, accordingly, to a statistically significant (p < 0.001) increase in the energy charge by 35.1 % compared to the control animals. Inhibition of stress-induced hyperactivation of lipid peroxidation in the gastric mucosa is one of the mechanisms of its antiulcer activity.
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