29 May 2023 in Drug development & registration
Introduction. One of the most progressive directions of the modern stage of development of biology is the deepening of knowledge about the mechanisms of regulation of metabolic processes, in particular about signal molecules that transmit information to the cell through ion channels and nuclear receptors associated with G-protein or with enzymatic activity. The nuclear Farnesoid X receptor (FXR) is mainly expressed in the liver and intestines, it regulates key genes that provide the processes of synthesis, transport and reabsorption of bile acids, and is also involved in the metabolism of lipids and carbohydrates.Aim. To evaluate the effect of a farnesoid X receptor agonist on postprandial lipemia in rats fed a supraphysiological fat diet.Materials and methods. An experimental, prospective, controlled, unblinded, randomized study was conducted to study the effect of a farnesoid X receptor agonist (obeticholic acid) on postprandial lipemia in rats receiving a diet containing a supraphysiological dose of fats.Results and discussion. It has been shown that when assessing postprandial lipemia, an oral test for tolerance to supraphysiological doses of fat with the determination of the initial lipid profile parameters and 4 hours after exercise has a sufficiently high information content. It was found that in animals that received a diet containing an increased amount of fat for 28 days, there was an imbalance in lipid metabolism with activation of their absorption in the intestine, but a "slow" reaction of the mechanisms of intermediate lipid metabolism, which was accompanied by the accumulation of triglycerides and cholesterol in the blood of hungry rats, chylomicrons and LDL. At 4 hours post-feeding, these animals showed abnormal increases in triglycerides and cholesterol.Conclusion. The use of obeticholic acid harmonizes lipid metabolism against the background of alimentary fat load, due to the activation of farnesoid X-receptors of the intestine and liver, which is manifested by a simultaneous increase in the intensity of lipid absorption processes and their intermediate metabolism. As a result, the risk of hyperchylomicronemia, hypercholesterolemia and hypertriglyceridemia is eliminated, the likelihood of developing secondary hyperlipedemia, insulin tolerance and functional overload (or pathology) of the liver is reduced.
29 June 2023 in International Journal of Veterinary Medicine
To date, the assessment of the functional state of the hepatobiliary system by analyzing changes in the clearance of exogenous caffeine is one of the most promising hepatic stress tests. The purpose of the study was to establish the pharmacokinetic change in the levels of exogenous caffeine in the blood plasma of laboratory animals in order to further induce various liver pathologies and subsequently assess the change in its clearance. For the study, non-linear laboratory rats were used (18 males, 18 females, average live weight 180 g ± 4%, age 3 months), Of the experimental animals, 3 groups were formed (6 females and 6 males each), each of which was injected subcutaneously with a 20% solution of caffeine sodium benzoate (Mosagrogen LLC, Russia) in increments of 50 mg/kg (50, 100, 150) in terms of pure caffeine.When using dosages of 100 and 150 mg/ kg, we noted a non-linear biotransformation of the test substance, namely, peak concentrations 4 hours after administration, which is also a standard pharmacokinetic indicator for dosages passing along the upper limit of the therapeutic latitude of the drug and is due to the fact that that at such dosages, the cytochrome P-450 enzyme system does not differ in reactivity compared to the absorption time of the substance.As a result of the experiment, we established the initial and peak levels of caffeine for further study of its changes during the artificial induction of hepatopathy of various origins in a specific experimental group of laboratory animals. We also noted the absence of dependence on the sex of the listed levels, and such results are consistent with the data obtained by other researchers.
15 December 2023 in Agricultural science Euro-North-East
In present-day conditions of industrial agriculture, the animal's body works at the limit of its capabilities, which leads to degenerative diseases of various organs and systems. The development of ergonomic ways of modern diagnosis of these pathologies at the early stages contributes to the maintenance of quantitative and qualitative indices of productivity of animals and to the extension of the time of their economic use. The liver with a great number of functions performed is subjected to the highest load. The aim of the article is to review the available clearance tests in order to diagnose the pathology of the hepatobiliary system of animals at the early stage, considering advantages and disadvantages of the tests. As the result of the search of themed issues in various bibliographic databases there have been selected 45 mostly cited scientific articles. The article reviews such clearance tests as indocyanine green clearance test, aminopyrine breath test, sorbitol elimination test, galactose elimination test, phenylalanine breath test, and hepatobiliary scintigraphy method. Functional tests allow not only diagnosing and differentiating hepatopathologies, but also visualizing their course and liver recovery. Unlike laboratory tests, clearance tests make it possible to evaluate the work of the liver in dynamics. The disadvantages of clearance tests are lack of information for their wide use and frequency of particular differences in elimination of specific substances. To reduce the proportion of existing shortcomings, it is possible to combine clearance tests with other laboratory methods for diagnosing hepatopathy in animals.
27 April 2022 in International Journal of Veterinary Medicine
The fish liver is an important organ involved in the complex metabolism of bile and bile acids. The biochemical reactions that occur during this process directly depend on the functional state of the digestive system and fish nutrition. Knowledge of the features of bile acid metabolism will allow designing the cheapest and at the same time effective drugs for the pharmacological correction of hepatopathy. The composition of bile acids depends on the type of food, so in fish such as pike, perch, carp, cholic and deoxycholic acids conjugated with taurine are more common. In predatory fish, cholic acid predominates, in contrast to benthivorous fish. Substances secreted with bile do not participate in the general metabolism of tissues, so that hepatocytes do not need to constantly secrete large volumes of bile.The metabolism of bile acids is carried out by the liver and is called the enterohepatic circulation. It all starts with the biological precursor of bile acids - cholesterol. Cholesterol in the body is formed during the absorption of lipids in the intestine. Two-thirds of exogenous cholesterol is excreted from the body in the form of bile acids. As a result of transformation by hepatocytes, primary bile acids are formed - cholic and chenodioxycholic. Then they are cojugated with taurine or glycine in the C-24 region of the carboxyl group and are excreted from hepatocytes continuously through the bile ducts to the gallbladder and further to the intestine. In the intestine, under the influence of microbial metabolites, they are hydroxylated and converted into secondary bile acids. Cholic becomes deoxycholic, and chenodisoxycholic becomes lithocholic. A small amount of bile acids are in a free state and form paired compounds. 90% of bile acids in the intestine form complexes of choleic acids in combination with fatty acids, which are absorbed through the wall of enterocytes. In enterocytes, these complexes again disintegrate and bile acids again enter the liver through the portal vein. Thus the circle of metabolism is closed.
19 June 2023 in International Journal of Veterinary Medicine
In modern clinical veterinary practice, in the overwhelming majority of cases, the diagnosis associated with pathologies of the hepatobiliary system is established on the basis of a combination of clinical, laboratory and instrumental data, which is a rather laborious and cost-intensive process, which makes it relevant to search for new methods with more relevant. Laboratory assessment of the hepatobiliary system has several goals, including: determining the presence of hepatobiliary pathology, determining the presence of liver disease, including primary or secondary hepatitis, determining the definitive type of liver disease, and monitoring response to therapy or disease progression. We have comprehensively analyzed existing studies in the field of using various methods for diagnosing pathologies of the hepatobiliary system, identifying the most promising approaches from the point of view of veterinary hepatology for their further possible introduction into industry practice. The search and processing of scientific publications was carried out according to the recommendations of H. Snyder [10] for writing review articles. An assessment is given to the positive and negative sides of each technique.Based on the analyzed literature, it can be concluded that, despite the knowledge of the issues of hepatology and the diagnosis of liver diseases, there are gaps and weaknesses in any diagnostic model. Thus, one potential diagnostic model that is promising but little studied is the use of clearance tests. Functional tests allow not only to diagnose and differentiate hepatopathologies, but also to visualize their course and liver recovery.Also, unlike statistical tests, clearance tests allow you to evaluate the work of the liver in dynamics.