Выявление омик-маркеров негативных эффектов, ассоциированных с аэрогенным комбинированным воздействием соединений алюминия и фтора

Abstract

At present, it is relevant to study simultaneous combined impacts exerted by chemicals on developing adverse health effects. It is also becoming vital to search for molecular indicators of adverse effects with the altered expression level. This alteration makes it possible to determine peculiarities of molecular and cellular pathogenesis mechanisms regarding a number of non-communicable diseases under exposure to a mixture of chemicals. Our research goal was to comparatively analyze and identify identical omic-markers of adverse effects under experimental and actual combined aerogenic exposure to aluminum and fluoride compounds. We substantiated molecular markers of prenosological changes by sequential implementation of an algorithm which included identifying altered proteins and peptides in blood plasma which were identical both under experimental and actual exposure; detecting and quantifying cause-effect relations between identical proteins and peptides and concentrations of aluminum and fluoride ion in urine. The research results indicate that long-term combined aerogenic exposure to aluminum and fluoride compounds in low average daily doses (0.0005 mg/(kgday) and 0.002 mg/(kg*day) accordingly) causes elevated concentrations of aluminum (by 2.8 times higher) and fluoride-ion (by 1.8 times higher) in exposed children’s urine. This fact is verified by experimental research with its focus on combined exposure to the examined chemicals. We were able to substantiate identical omic-markers, J-chain of immunoglobulin and Kelch-like protein 4 (KLHL4 gene), under simultaneous exposure to aluminum and fluoride compounds both under experimental and actual combined aerogenic exposure. We proved a cause-effect relation between levels of identical proteins and concentrations of aluminum and fluoride ion in urine under simultaneous exposure to the mixture of the examined chemicals. Identified protein markers in blood plasma give an opportunity to predict future adverse effects including developing immunoglobulins A and M deficiency with subsequent humoral immunity failure when J-chain of immunoglobulin is expressed; occurring sclerotic and inflammatory changes in vascular walls when Kelch-like protein 4 is expressed. These predicted adverse effects can be estimated as resulting from simple summated (additive) toxic impacts exerted by aluminum and fluoride under simultaneous combined aerogenic exposure to both chemicals.