Masliuk A. Pharmaco-toxicological characteristics of gadolinium and lanthanum orthovanadate nanoparticles

The solves a scientific and applied problem within the framework of the problem of biosafety (toxicity, pharmaco- and toxicodynamics and kinetics) of gadolinium and lanthanum orthovanadates nanoparticles, namely screening of the quality of hatching eggs and feed for meat-producing chickens in terms of vitamins and trace elements and its analysis; toxicity parameters were established in terms of pharmacodynamics and toxicodynamics of nanoparticles of rare earth elements (gadolinium and lanthanum) orthovanadates using white rats under conditions of feed stress in a subchronic experiment; pharmacodynamics of gadolinium and lanthanum orthovanadates nanoparticles in the body of broiler chickens was investigated; a methodology for determining gadolinium and lanthanum in biological material was developed and validated; the pharmacokinetics of rare earth elements in the body of broiler chickens was determined; the quality indicators of broiler chickens meat in the case of using gadolinium and lanthanum orthovanadates nanoparticles were investigated; recommendations for determining the antibacterial effect and cytotoxicity parameters of metal nanoparticles on prokaryotic and eukaryotic cell models were systematized. The scientific novelty of the results is that the quality of hatching eggs and feed for meat-producing chickens was screened for vitamins and trace elements and analyzed for the first time in Ukraine. It was found that there is a tendency to reduce the content of vitamins B2 and E, carotenoids, and selenium in feed and eggs. For the first time, the pharmacodynamics and toxicodynamics of nanoparticles of rare earth elements (gadolinium and lanthanum) orthovanadates were studied using white rats under conditions of feed stress in a subchronic experiment. The adaptogenic effect of both REEs in the dose range (≈ 0.03-0.15 mg/kg body weight), corresponding to (0.2-1.0) mg/dm3 of drinking water, was established. For the first time in Ukraine, a method for the determination of REEs (lanthanum and gadolinium) in biological samples using inductively coupled plasma atomic emission (ICP OES) was developed and validated, and the methodology for sample preparation in different matrices was adapted. For the first time, the effect of gadolinium and lanthanum orthovanadates nanoparticles on the body of broiler chickens was studied, the parameters of pharmacodynamics and pharmacokinetics, as well as the quality of meat obtained from them were determined. It was found that administration of gadolinium and lanthanum orthovanadates to broiler chickens with drinking water at a concentration of 0.2 mg/dm³ for 10 days caused a decrease in certain lipid metabolism parameters (total cholesterol and triglycerides), non-protein nitrogen compounds (uric acid) and lipid peroxidation indicators against the background of activation of carbohydrate metabolism and activity of hepatospecific enzymes, promotes better absorption of vitamins B2, A and E and trace elements - selenium, copper and zinc, leads to an increase in the mass fraction of protein and a decrease in the mass fraction of fat in the meat. In this case, gadolinium orthovanadate nanoparticles show the ability to "materially" accumulate, as evidenced by the content of gadolinium in all organs and tissues studied, while lanthanum orthovanadate nanoparticles are absorbed in the body in much smaller amounts. For the first time in Ukraine, the recommendations for determining the antibacterial effect were systematized and the parameters of cytotoxicity of metal nanoparticles were established on a model of prokaryotic and eukaryotic cells. The systematization of recommendations for determining the antibacterial effect and cytotoxicity parameters of metal nanoparticles on prokaryotic and eukaryotic cell models will facilitate the assessment of the toxicity of other rare earth metal nanoparticles.