Correction of oxidative stress in chronic phosphorus intoxication with a standardized polyphenol concentrate
2025-05-16 10:38
Project goal: to determine the likelihood of reducing the risk of phosphorus intoxication because of dietary intervention based on the use of grape polyphenol concentrate, according to biomarkers of oxidative stress and state of the gut microbiome in workers in the conditions of mining and processing of phosphate rock(including the production of yellow phosphorus)
Project description: The problem of phosphorus intoxication among workers at the enterprises of the phosphate industry is real for Kazakhstan due to the intensive development of phosphate ores, the production of poisonous yellow phosphorus and phosphate mineral fertilizers. Since the general mechanism of phosphate intoxication is cytotoxicity, increased release of free radicals, expression of lipid peroxidation, depression of the antioxidant system, as well as the formation of a specific type of intestinal microbiota, the antiradical, antioxidant, cytoprotective effects of grape polyphenols can be potential factors to counteract the development of phosphorus intoxication. The project is aimed at solving the problem of the risk of industrial intoxication of workers in the extraction and processing of phosphorus. The object of the study is a dietary product - a biologically active food supplement - a concentrate of grape polyphenols certified in the Republic of Kazakhstan. The expected number of study participants is at least 150 volunteers. Biomarkers - the level of phosphorus concentration in blood serum, the level of antioxidant activity of blood plasma, the level of malondialdehyde, phylogenetic characteristics and metagenomic profile of the intestinal microbiome. The main result of the study will determine the likelihood of reducing the risk of phosphorus intoxication by biomarkers of oxidative stress and the state of the intestinal microbiome in workers in the conditions of mining and processing of phosphorite ore (including the production of yellow phosphorus and phosphate mineral fertilizers). It is supposed to draw up Methodological recommendations to reduce the risk of manifestations of industrial phosphorus intoxication with the help of a dietary intervention based on the use of grape polyphenol concentrate. The scope of the expected results is the field of occupational diseases, preventive medicine, nutrition. The target consumers of the expected results are the sanitary and preventive and medical service of the enterprises of the phosphorus industry of the Republic of Kazakhstan. The possibility of commercialization of the obtained scientific results in the form of the development of a new dietary product to reduce the risk of phosphorus intoxication is supposed. The results of the project can have social and economic effects in reducing the clinical manifestations of phosphorus intoxication and, reducing the days of disability of workers due to dietary inhibition of the development of phosphorus intoxication.
Expected results: Forms of project implementation - publication of articles on the results of the project. Based on the results of the work performed, it is planned to publish: - at least 3 (three) articles and (or) reviews in peer-reviewed scientific publications indexed in the Science Citation Index Expanded Web of Science database and (or) with a CiteScore percentile in the Scopus database of at least 35 (thirty-five) ; - either at least 2 (two) articles and (or) reviews in peer-reviewed scientific publications indexed in the Science Citation Index Expanded Web of Science database and (or) with a CiteScore percentile in the Scopus database of at least 35 (thirty five) ), and at least 1 (one) patent included in the Derwent Innovations Index database (Web of Science, Clarivate Analytics); - as well as at least 1 (one) article or review in a peer-reviewed foreign or domestic publication recommended by CQAES MES RK; - at least 2 (two) articles and (or) reviews in peer-reviewed scientific journals, indexed in the extended scientific citation index and included in the 1 (first) and (or) 2 (second) quartile by the impact factor in the Internet database Science and/or have a CiteScore percentile in the Scopus database of at least 65 (sixty-five); - at least 1 (one) article or review in a peer-reviewed scientific publication, indexed in the extended science citation index and included in the 1st (first) quartile by impact factor in the Web of Science database and (or) having a CiteScore percentile rating in the Scopus database is not lower than 80 (eighty). 2 articles are expected to be published. Suggested publications for publishing the results of the project: Scientific reports (Q1 quartile, 91% percentile). 2) publication of monographs, books and (or) chapters in books of foreign and (or) Kazakh publishing houses - not provided 3) obtaining patents in foreign patent offices (European, American, Japanese), Kazakh or Eurasian patent offices - not provided 4) development of scientific, technical, design documentation - not provided; 5) The results of the work will be distributed among the members of the Federation of European Microbiological Societies and the International Consortium of the Human Microbiome, including the presentation of the results obtained at the conferences "International Conference on Pharmacy and Pharmacology ICPP" August 10-11, 2023 in New York, USA and "ICBICDA 2024: 18. International Conference on Biomedical Intelligence and Clinical Data Analysis", January 21-22, 2024, London, UK. 6) As the main result of the research, it is expected to obtain evidence of a reduction in the risk of phosphorus intoxication among workers in conditions of constant industrial contact during the extraction and processing of phosphates. The main result will be expressed in quantitative, statistically significant changes in biomarkers characterizing the processes of lipid peroxidation, antioxidant activity of blood plasma, phylogenetic characteristics and metagenomic profile of the intestinal microbiome after dietary intervention in the form of grape polyphenol concentrate intake. The main result of the study will determine the likelihood of reducing the risk of phosphorus intoxication by biomarkers of oxidative stress and the state of the intestinal microbiome in workers in the conditions of mining and processing of phosphorite ore (including the production of yellow phosphorus and phosphate mineral fertilizers). It is supposed to draw up Methodological recommendations to reduce the risk of manifestations of industrial phosphorus intoxication with the help of a dietary intervention based on the use of grape polyphenol concentrate. The scope of the expected results is the field of occupational diseases, preventive medicine, nutrition. The target consumers of the expected results are the sanitary and preventive and medical service of the enterprises of the phosphorus industry of the Republic of Kazakhstan. The possibility of commercialization of the obtained scientific results in the form of the development of a new dietary product to reduce the risk of phosphorus intoxication is supposed. The results of the project can have social and economic effects in reducing the clinical manifestations of phosphorus intoxication and, reducing the days of disability of workers due to dietary inhibition of the development of phosphorus intoxication.
Methodology: 1. Preparation of documents in accordance with the GCP standard for conducting a randomized, placebo-controlled clinical trial of the effectiveness of grape polyphenol concentrate under conditions of industrial phosphorus intoxication. Drafting of an Agreement with Kazphosphate LLP, Clinical Study Protocol, Investigator's Brochure, Information for Study Participants, Participants' Insurance Documents. 2. Screening of study participants (men and women, aged 18 - 50 years, directly involved in the extraction and processing of phosphorite ore, the production of yellow phosphorus and its derivatives, phosphate mineral fertilizers) according to the inclusion criteria and the formation of the studied cohorts: workers with an experience of 1- 2 years (at least 60; workers with an experience of 3-5 years (at least 60). The comparison group (healthy control) will be selected men and women, aged 18-50, engaged in agriculture, not related to the use of mineral fertilizers and living in an ecologically clean region of Kazakhstan (at least 30).Initially, biomarkers are assumed: the level of phosphorus concentration in blood serum, the level of antioxidant activity of blood plasma, the level of malondialdehyde (MD), phylogenetic characteristics and metagenomic profile of the intestinal microbiome. 3. Randomization to study groups 1:1: dietary intervention - ingestion daily by mouth 30 minutes before a meal or 2 hours after a meal at a dose of 15 ml of a certified dietary supplement (BAA) - grape polyphenol concentrate (20 mg / ml a) 5 days a week for 3 months; placebo - grape juice in a similar dose and according to a similar regimen. Upon completion of the intake of dietary supplements or placebo - control of the level of biomarkers (antioxidant activity of blood plasma, MD, phylogenetic characteristics and metagenomic profile of the intestinal microbiome. 4. Monitoring the long-term effects of taking dietary supplements (grape polyphenol concentrate) 1 year after the end of the intake - monitoring the level of biomarkers (antioxidant activity of blood plasma, MD, phylogenetic characteristics and metagenomic profile of the intestinal microbiome. 5. Analysis of the results, formation of recommendations on the likelihood of reducing the risk of initial phosphorus intoxication and inhibition of chronic phosphorus intoxication when taking a biologically active food supplement - grape polyphenol concentrate.