Rat Endogenous Intoxication Level under Experimental Nephropathy and Reduced Glutathione Application

The purpose of the study, therefore, was to investigate the content of substances of low and medium molecular weight, total and tyrosine-containing peptides and to assess the level of endogenous intoxication of the rat organism under conditions of experimental nephropathy and the use of reduced glutathione. Materials and methods. The experiment was performed on nonlinear white rats weighing 160-180 g. The animals were in a vivarium with a constant temperature (18-22°C), relative humidity (50-55%) in individual exchange cells in the formed groups, on a constant balanced mode of a diet with free access to water and food. Nephropathy was modeled by a single intraperitoneal injection of folic acid at a dose of 250 mg/kg. Glutathione was administered intragastrically (100 mg/kg) for 7 days after folic acid intoxication. Results and discussion. Under conditions of nephropathy in the blood serum of rats, an increase in the level of molecules of average weight was observed by 2 times, as well as low-molecular substances by 1.6 times compared with the control. Daily administration of reduced glutathione to animals with nephropathy for 7 days led to a decrease in the level of substances of medium and low molecular weight by 21% and 27% in comparison with the indicators of animals with nephropathy, but still significantly differed from the control indicators. Against the background of an increase in the content of total oligopeptides by 2.2 times in the blood serum of experimental rats, the level of tyrosine-containing peptides increased by 1.8 times in comparison with the control. The introduction of glutathione to rats with nephropathy led to a decrease in these parameters by 40 and 35%, respectively, compared with the experimental control. As a result of the established changes in the level of albumin and average weight molecules in the blood serum of animals, under conditions of nephropathy, an increase in the coefficient of endogenous intoxication was observed by 2.3 times. This imbalance indicates a violation of the processes of detoxification of endogenous metabolites in the liver of animals under conditions of nephropathy. In the groups of animals with nephropathy, which were injected with an antioxidant, the coefficient of endogenous intoxication decreased by 41% compared with animals that did not receive glutathione, but this indicator did not return to the level of control values. Conclusion. Thus, under the conditions of experimental nephropathy in the blood serum of rats, an increase in the content of total and tyrosine-containing peptides, substances of low and medium molecular weight, as well as an increase in the values of the intoxication coefficient was observed, which indirectly indicates a violation of the processes of detoxification of endogenous metabolites in the liver of experimental animals with kidney pathology. In the group of animals with nephropathy that received reduced glutathione for 7 days, only a tendency towards normalization of the studied parameters characterizing the level of endogenous intoxication under conditions of nephropathy was noted

EFFECT OF 7-DAY INTRODUCTION OF GLUTATHIONE ON ACTIVITIES OF H2S-PRODUCING ENZYMES IN THE LIVER OF RATS UNDER EXPERIMENTAL NEPHROPATHY CONDITIONS

Introduction. Kidney diseases are a worldwide health problem. The renal dysfunctions cause the production of reactive oxygen species and can co-exist with different liver disease, or stimulate their development, so scientists are becoming more interested in the study of the influence of antioxidants such as glutathione on metabolic pathways of the body under conditions of different disease. Hydrogen sulfide has anti-inflammatory, anti-oxidant and anti-apoptotic effects that are mediated by its ability to downregulate the synthesis of lipid peroxides and reactive oxygen species-producing enzymes and may play an important role in the mechanism of development of nephropathy. The aim of the study – to learn the effect of glutathione introduction within 7 days on the system of H2S production in the liver of rats under conditions of experimental nephropathy. Research Methods. The experiment was conducted on albino mature male rats. The animals in experimental group were administered a single intraperitoneal dose of folic acid (250 mg/kg). Glutathione was introduced intragastral (100 mg/kg) within 7 days after intoxication. The activity of H2S-producing enzymes, the concentration and production of H2S were measured in the liver. Results and Discussion. Under conditions of experimental nephropathy there was a decrease in the concentration and production of hydrogen sulfide compared with the control group. The introduction of glutathione increased the content of hydrogen sulfide and promoted the growth of the activities of H2S-producing enzymes in the liver of rats. Conclusions. It was found that the content and production of hydrogen sulfide in the group of animals with nephropathy were diminished by a decrease in the activities of hepatic H2S-producing enzymes. The introduction of glutathione increased the content of hydrogen sulfide by stimulation the activities of cystathionine-β-synthase and cysteinaminotransferase in the liver of rats. As reasons for this effect, antioxidant properties of glutathione and the possibility of including tripeptide as a source of cysteine in the synthesis of hydrogen sulfide are considered.

Antiproteinuric and nephroprotective activity of some peptide drugs in experimental nephropathy

Цель исследования - изучение антипротеинурической и нефропротекторной активности пептидных препаратов при нефропатии на модели экспериментального аутоиммунного нефрита Хейманна. Методы. Данную патологию моделировали на крысах путем введения антигенной суспензии почки материнской особи в полном адъюванте Фрейнда (в/бр). Для оценки эффективности препаратов использовали показатели функции почек и системы иммунитета. Результаты. Препарат эпиталамин обладал наибольшим влиянием на скорость клубочковой фильтрации и величину гематурии, кортексин наиболее эффективно уменьшал протеинурию. Тимодепрессин оказывал наиболее выраженное позитивное влияние на уровень общего белка в крови. Эпиталамин и кортексин в наибольшей степени уменьшали уровень общего холестерина. Эпиталамин и тимодепрессин максимально снижали уровень мочевины. Все исследованные препараты в равной мере приводили к нормализации уровня креатинина, функционального состояния иммунитета, сопоставимо повышали уровень кортизола, сниженный при патологии. Препарат эпиталамин, в отличие от тимодепрессина и кортексина, вызывал частичную нормализацию уровня CD8+ Т-клеток и подавлял продукцию криоглобулинов. Эпиталамин обладал максимальной суммарной эффективностью в отношении показателей эндотоксикоза. Выводы. Полученные данные свидетельствуют о значительной клинической эффективности пептидных биорегуляторов в отношении большинства нарушенных показателей функциональной активности почек и иммунной системы, а также эндотоксикоза. The aim of the study was to study the antiproteinuric and nephroprotective activity of some peptide drugs using the model of experimental Heymann active nephritis. Methods. Heymann’s active nephritis was modeled on rats by injecting an intraperitoneal antigenic suspension of the mother’s kidney in Freund’s complete adjuvant. To assess the effectiveness of the drugs, indicators of kidney function and immunity system wereused. Results.The epithalamine was shown to bethe most effective drugthat increasedthe glomerular filtrationrate and decreasedthe level of hematuria.Cortexin reduced proteinuria more than the other peptides. The most pronounced positive effect on the level of total protein in the blood was seen withthymodepressin. Epithalamin and cortexin reduced the level of total cholesterol. Epithalamin and timodepressinmaximally decreased the level of urea. All the studied drugs equally led to the normalization of creatinine level and functional immunity, as well as increased the level of cortisol reduced as the result of pathology. Epithalamin normalized the level of CD8+ T-cells and suppressed the production of cryoglobulins. Epithalamin was the most effective drug reducingendotoxicosis. Conclusion. The obtained results demonstrated that the use of peptide bioregulators in the treatment had positive effects on the functional activity of kidneys, the immune system and markers of endotoxicosis.