The study of the effect of sodium nitrite on the bodies of rats of different ages under the influence of a 45-day tobacco intoxication, as well as the search of adequate correction methods using antihypoxants and enterosorbents under these conditions, is presented in the thesis.
It has been established, that during the whole experiment, after the affection of the rats, the hyperproduction of active forms of oxygen is present. Hyperproduction of ROI caused activation of free radical oxidation processes (increased lipoperoxidation and oxidative modification of proteins) in the animals’ body.
Additionally, a hypoxic state developed in the body that was caused by the enhanced development of methemoglobin and carboxyhemoglobin under the influence of toxic factors. The highest content of carboxyhemoglobin in blood was evidenced during the whole period of TS affection in the immature rats. The generated toxic products caused the destruction of biomembranes and release of intracellular components into the blood. Moreover, the results of studies of organ-specific enzymes (aminotransferases, gamma-glutamyltranspeptidases, lactate dehydrogenase, and alkaline phosphatase) in blood serum proved the damage to membrane structures of hepatocytes. Under the given conditions, secondary endogenous toxins accumulated in the body. The degree of endogenous intoxication was defined by average weight molecules, the content of which significantly increased in blood serum of the rats of all age groups after the affection.
Endogenous intoxication caused changes in the antioxidant defense system, in particular, the activity of the enzyme level of the antioxidant system decreased. With underlying nitrite-tobacco toxicity, the progressive decrease in reduced glutathione content in the liver, lungs, kidneys, and myocardium of the rats of all age groups was evidenced, but the most significant changes were present in the immature rats.
The changes in the mitochondrial system of oxidation, in particular, the decrease of succinate-dehydrogenase and cytochrome-oxidase activity, caused a decrease of ATP synthesis in the body.
Additionally, the accumulation of intermediate toxic products of neutralizing of sodium nitrite and components of tobacco smoke as well as free-radical oxidation products was accompanied by the development of inflammatory processes, as evidenced by the imbalance of pro- inflammatory and anti-inflammatory cytokines and increase in C-reactive protein content in serum – a marker for early diagnosis of inflammation. The highest content of this index was evidenced in blood serum of the senile rats poisoned by both toxicants.
With underlying oxidative stress development caused by the influence of toxicants, the dysfunctioning of the NO-system and development of nitro-oxidative stress was evidenced, which was manifested by increased activity of inducible NO-synthase and decreased activity of its endothelial isoform. It was established that after the affection of rats by sodium nitrite with underlying tobacco intoxication, the activity of iNOS in serum progressively increased in all age groups. The activity of eNOS in blood serum of the immature rats decreased nearly equally in all stages of the study and at the end of the experiment was below the norm by 56 %.
Microscopic examination of organs revealed that structural reorganization of lungs, liver, kidneys, myocardium of the animals of all age groups was characterized by changes in vascular bed, main morphofunctional components.
The most pronounced metabolic changes with underlying nitrite-tobacco intoxication were evidenced in the immature rats that were proved by the experimental data.
The expediency of the use of mildronate, antihypoxant, and carboline, enterosorbent, in cases of nitrite-tobacco affection has been proved. A higher efficacy of mildronate, the drug of metabolic action, in cases of the revealed changes has been proved.
