An Update on Glutathione's Biosynthesis, Metabolism, Functions, and Medicinal Purposes.

Glutathione (GSH) has been the focus of increased scientific interest in the last decades. It plays a crucial role in all major physiological processes by supplying antioxidant defenses through participating in cellular redox reactions in the human body and other living organisms. GSH also participates in detoxifying xenobiotics, protecting protein thiols from crosslinking and oxidation, regulating the cell cycle, storing cysteine, etc. The significant role of GSH in the most important physiological processes has been highlighted, such as maintaining the redox balance and reducing oxidative stress due to its ability to inactivate the reactive oxygen, nitrogen, and sulfur species. It can also enhance metabolic detoxification and regulate the function of the immune system. All of these characteristics make it a universal biomarker since its proper balance is essential for improving health and treating some age-related disorders. This review presents a current concept of the synthesis and metabolism of GSH; its main functions in a living organism, and as a precursor and cofactor; data on the use of GSH for medicinal purposes in the prevention and treatment of some diseases, as well as a nutritional strategy to maintain a normal pool of GSH in the body. The data were gathered by searching relevant information in multiple databases, such as PubMed, Scopus, ScienceDirect, and Google Scholar.

EFFECT OF DRY EXTRACT FROM REISHI MUSHROOMS ON THE STATE OF ANTIOXIDANT SYSTEM IN RATS WITH DMH-INDUCED COLON CARCINOGENESIS.

OBJECTIVE: The aim: To study pro- and antioxidant systems indicators in rats with chemically induced colon carcinogenesis on the background of the reishi mushrooms dry extract use. PATIENTS AND METHODS: Materials and methods: The study was performed on 120 white male rats. Chronic oncogenic intoxication was modeled by administering 1,2-dimethyl¬hydrazine (DMH) hydrochloride for 30 weeks (1 time per week). A dry extract from the reishi mushrooms was administered intragastrically daily at a dose of 100 mg/kg of the animal's body weight. Blood and liver samples were taken for research monthly. The state of the pro- and antioxidant systems was studied by the content of oxidative modification of proteins products, superoxide dismutase and catalase activity, contents of reduced glutathione and ceruloplasmin. RESULTS: Results: An increase in the activity of free radical oxidation processes after DMH-induced colon carcinogenesis in rats is evidenced by a decrease in the super-oxide dismutase activity, catalase activity, content of reduced glutathione, an increase in the content of ceruloplasmin and products of oxidative modification of proteins in the blood serum and liver of animals. The effectiveness of the dry extract of reishi mushrooms and its positive effect on the state of pro- and antioxidant systems was experimentally proved. CONCLUSION: Conclusions: The use of the dry extract of reishi mushrooms under conditions of DMH-induced colon carcinogenesis in rats led to normalization of the anti¬oxidant protection system state and the reduction of oxidative stress.

Evaluation of membrane-destructive processes in rats with induced carcinogenesis of the colon using the cytostatic vincristine.

Background: Every year the number of cases of colorectal cancer increases. Chemotherapy is one of the main methods of treating cancer. However, chemotherapeutic treatment of colorectal cancer is inextricably linked to hepatotoxic reactions. Objective: The aim of this study was to investigate the effect of the cytostatic vincristine on the background of previous enterosorption correction with the drug aut-m in adenocarcinoma of the colon. Material and methods: To simulate carcinogenesis, dimethylhydrazine (DMH) was administered subcutaneously to 77 rats for 30 weeks at a dose of 7.2 mg/kg body weight. After simulation of colon cancer, the animals were intragastricly administered entorosorbent at a dose of 1 ml of suspension (corresponding to 0.2 g of net weight of the drug) per 100 g of body weight of the animal, daily for 21 days. After detoxification therapy, rats with simulated carcinogenesis were administered the daily cytostatic vincristine at a dose of 0.23 mg/kg for 14 days. Results: It was found that prolonged administration of dimethylhydrazine is accompanied by destructive changes in plasma membranes, as evidenced by increased activity of enzymes alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and serum urea. Conclusions: The used sorbent aut-m showed an effective effect on reducing the manifestations of cytolytic processes in induced carcinogenesis, as indicated by the normalization of the studied parameters. The cytostatic vincristine, which was used in rats with induced colorectal cancer after enterosorption therapy, did not significantly affect the enhancement of cytolytic processes, which confirms the effectiveness of previous sorption measures under these conditions.

Application of the thick extract from Maitake mushrooms for correction of metabolic disorders under the paracetamol hepatitis in rats.

It is known that the violation of one or more functions of the liver, where the basic biochemical processes take place, is reflected in the functional state of many organs and systems, causing severe consequences. For the effective treatment of the hepatobiliary system diseases the drugs from fungi and plant materials are promising, the ingredients of which are close to natural metabolites, have different mechanisms of hepatoprotective action and, in general, can have a positive effect on liver function. AIM: The aim of the research was to investigate the hepatoprotective properties of the Maitake mushrooms thick extract in the experiment on rats with paracetamol (acetaminophen)-induced hepatitis. MATERIALS AND METHODS: The study was performed on 60 white male rats weighing 180-210 g and aged 6-6,5 months. Rats were divided into 10 groups, each of which included 6 animals. Acute hepatitis was simulated by acetaminophen intragastrically administering at a dose of 1250 mg/ kg of body weight 1 time per day as a suspension in 2% starch gel solution for 2 days. Correction of the toxic lesions was performed with a thick extract of Maitake mushrooms, which was administered intragastrically 2 hours before the introduction of acetaminophen and daily after the lesion at a dose of 150 mg/kg of body weight. "Silibor" (active basis - silymarin) was chosen as a comparison drug, which was administered according to the same scheme as Maitake extract at a dose of 20 mg/kg of animal body weight. On the 3rd, 7th and 10th days from the onset of the lesion, rats were euthanized using sodium barbamyl. Liver homogenate and blood serum were tested. Blood was taken from the hearts of animals. Endogenous intoxication of animals after the introduction of corrective factors was assessed by the activity of ALT, AST, GGTP, LF and the size of the thymol sample. All changes were confirmed by parametric and nonparametric methods of statistical analysis of the results of the study. RESULTS: The expressed cytolysis of hepatocytes, after administration to rats of toxicant, on the basis of research of the activity of aminotransferases, gamma-glutamyltranspeptidase, alkaline phosphatase and thymol sample size is proved. The results of the experiment were confirmed histologically. The introduction of a thick extract of Maitake mushrooms contributed to the normalization of the studied indicators. CONCLUSIONS: The application of the Maitake mushrooms thick extract as a corrective factor in the simulated acetaminophen hepatitis indicates its hepato-, cytoprotective and antioxidative properties.

State of humoral immunity and cytokine profile in rats under experimental carcinogenesis with applying enterosorporation chemotherapeutic factors.

The number of cancer patients is growing in all countries. Due to the malignant progression of cancer, inflammatory processes are observed, which are inextricably linked with the response of the immune system. AIM: The aim of this research was to study the effectiveness of the cytostatic Vincristine on the background of sorption correction of disorders by the carbon sorbent AUT-M (activated carbon tissue material) in adenocarcinoma of the colon. MATERIALS AND METHODS: To simulate carcinogenesis, 1,2-dimethylhydrazine (DMH) was administered subcutaneously to 76 rats for 30 weeks at a dose of 7.2 mg / kg body weight. The evolution of adenocarcinoma of the colon in experimental animals was confirmed by histological examination. After simulation of colon cancer, the animals were intragastrically administered entorosorbent at a dose of 1 ml of suspension (corresponding to 0.2 g of net weight of the drug) per 100 g of body weight of the animal, during 21 days. After detoxification therapy, rats with simulated carcinogenesis were administered the daily cytostatic Vincristine at a dose of 0.23 mg/kg for 14 days. In the above groups of experimental rats, the state of the humoral part of the immune system was studied by the content of serum IgA, IgM, IgG and circulating immune complexes. According to the content of pro- and anti-inflammatory cytokines, inflammatory processes in experimental animals with induced carcinogenesis of the colon on the background of enterosorption and cytostatic corrections were studied. The changes are confirmed by parametric and nonparametric methods of evaluation of the obtained data. RESULTS: It was found that long-term administration of the carcinogen is accompanied by changes in the humoral part of the immune system, as evidenced by the increase in serum IgA, IgM, IgG and CEC level. The results of the research showed that the introduction of 1,2- dimethylhydrazine to animals is accompanied by a change in the cytokine profile, increases the level of pro-inflammatory IL-6 and decreases the level of anti-inflammatory IL-4. CONCLUSIONS: Simultaneous use of enterosorption and cytostatic therapy helped to restore the cytokine balance and indicators of the humoral part of immunological protection.