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Registration Number

0216U002024, 0112U000542 , R & D reports

Title

Biochemical mechanisms of the toxicity of nanoparticles of different nature and other anthropogenic and biogenic toxicants in biological systems

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Head

Korda Mykhaylo Mykhaylovych,

Registration Date

18-01-2016

Organization

Horbachevsky Ternopil State Medical Academy

Description

It was demonstrated, that in animals carbon fullerene С60 nanoparticles increase oxidative stress, nitro-oxidative stress and hepatotoxicity in response to administering of the chemical toxin toluene. It was determined, that oral administration of lead nanoparticles against the background of ingesting water with sodium and potassium stearate changes the peripheral blood in rats as well as the indicators of lipid peroxidation in blood, liver and kidneys of white rats. Mathematical models were derived to quantitatively describe the processes of aggregation and sedimentation in particles of different sizes. Using these models, it is possible to calculate the time a given concentration of nano- and microparticles of varying dispersibility is reached at a certain point in space. It was determined that age influences the effect of paracetamol on lipid peroxidation activity and the state of anti-oxidative system. The most pronounced changes are observed in prepubescent and old animals. This could be due to the lower initial level of anti-oxidative system components. It was demonstrated, that in animals carbon fullerene С60 nanoparticles increase oxidative stress, nitro-oxidative stress and hepatotoxicity in response to administering of the chemical toxin toluene. It was determined, that oral administration of lead nanoparticles against the background of ingesting water with sodium and potassium stearate changes the peripheral blood in rats as well as the indicators of lipid peroxidation in blood, liver and kidneys of white rats. Mathematical models were derived to quantitatively describe the processes of aggregation and sedimentation in particles of different sizes. Using these models, it is possible to calculate the time a given concentration of nano- and microparticles of varying dispersibility is reached at a certain point in space. It was determined that age influences the effect of paracetamol on lipid peroxidation activity and the state of anti-oxidative system. The most pronounced changes are observed in prepubescent and old animals. This could be due to the lower initial level of anti-oxidative system components. Acute paracetamol poisoning against the background of 7-day administration of sodium nitrite is accompanied by more pronounced changes of the endogenic toxicity indicators and the state of plasma membranes as compared to paracetamol damage when it is administered alone. It was proven that 30-day long poisoning with copper sulfate, lead acetate and glyphosate (Round-up) in subthreshold doses (1/20 DL50) is accompanied by thy disruption of protein synthesis process of the liver. Elevated levels of bilirubin, urea, residual nitrogen, creatinine, medium weight molecules and increased activity of serum aminotransferase manifest the syndrome of intrahepatic cholestasis. Maximum permissible concentration of potassium stearate was determined as 0.25 mg/. It was demonstrated, based on the combined evaluation of experimental and commutative data, that potassium stearate can be classified as the chemical hazard of 4th level. It was demonstrated that protracted use by lab animals of water containing 0.1 mg/ dm3 of copper negatively affects anti-oxidant system of rat bodies, causing the suppression of catalase and peroxidase activity and increase of ceruloplasmin levels. It was determined that the damage to the cardiac muscle caused by toxic doses of adrenaline against the background of tetrachlormethane-induced hepatitis causes the activation of free radical oxidation processes and suppression of the antioxidant defense system. This is manifested in the decrease of both catalase activity and reduced glutathione level as well as the reduction of cruloplasmin levels in blood plasma, liver and heart of the rats. It was determined that simultaneous administration of malathion and tetrachlormethane to rats causes upsurge of lipid peroxidation processes and increased endogenic intoxication, which is indicated by the increased amount of middle weight molecules in blood serum and liver of the rats; it also causes damaging processes in the liver which are evidenced by high activity of transaminases in blood serum. Notably, the activity of acetylcholinerase is decreased, which is an indicator of toxic effect of malathion on acetylcholine hydrolysis and increase of excitability of the nervous system. The changes in the indicators of blood coagulation system and platelet levels under the experimental antiphospholipid syndrome were investigated in the model lines of female mice Balb/c. It was determined that the number of platelets decreased, the prothrombin time reduced, and prothrombin index increased in the cohort of animals with antiphospholipid syndrome. It is proven that in the pathogenesis of gum tissue inflammation caused by the toxic gram-negative microorganism lipopolysaccharides, an important role belongs to oxidative and nitro-oxidative stresses. The course LPS inflammation is significantly worsened given the underlying insulin-dependent diabetes, and periodontitis is significantly worsened given the chronic liver damage by allyl alcohol. It is shown that under the experimental hepatopulmonary syndrome in the lungs of rats, occurs the accumulation and activation of alveolar macrophages, that can be an important part of the pathogenesis of HPS as a source of vasodilating, angiogenic and proliferative growth factors such as inducible NO-synthase, vascular endothelial growth factor (VEGF) and platelet-derived growth factor. Also, the nitroxyderic processes are activated through significant increase of nitric oxide metabolites in blood serum and bronchoalveolar lavage.

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Боднар Ярослав Ярославович
Гонський Ярослав Іванович
Кашуба Михайло Олексійович
Кліщ Іван Миколайович
Козак Дарія Володимирівна
Кондратюк Володимир Андрійович
Корда Михайло Михайлович
Криницька Інна Яківна
Куліцька Марія Іванівна
Лихацький Петро Григорович
Марущак Марія Іванівна
Мерецький Віктор Миколайович
Мудра Алла Євгенівна
Острівка Оксана Іванівна
Підручна Світлана Романівна
Сельський Петро Романович
Фіра Людмила Степанівна
Федонюк Лариса Ярославівна
Шершун Галина Григорівна
Яремчук Ольга Зіновіївна