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Intensity of lipid and protein peroxidation and its regulation in rats after prolonged peroral administration of nanocomposites of metals (Ag, Cu, Fe, Mn dioxide)
The paper presents the results of 60-day oral exposure nanocomposite of metals (NcMe) consisting of aliquots amounts of colloid nanoparticles Ag, Cu, Fe and Mn dioxide, in different doses on the intensity of lipid and protein peroxidation and antioxidant status parameters of white rats’ blood plasma . Research has established that long-term per oral administration of compositional mixture of metals in different dispersed forms has caused in the blood of experimental rats multidirectional changes in formation of lipid peroxidation (LPO) products in the dynamics of the experiment.
In the blood plasma of rats treated with NcMe at a dose of 0,3 mg/kg body weight, only on the 90th day of the experiment there was determined the reduction of content of diene conjugates (DC) to 15,9% (p≤0,05), and at a dose of 4,0 mg/kg body weight, starting from the 30th day of the experiment – the content of both products of lipid peroxidation, which was the average for dine conjugates 30,0 %, and malondialdehyde (MDA) – 30,4% (p≤0,05) respectively relative values of these parameters in the control animals.
In rats treated with a mixture of metals in macro disperse form, there was set the reverse picture of the intensity of oxidative processes in comparison with after action of the mixture of metals in nanoparticle form. Thus, in the blood plasma of rats in this group there was determined the gradual strengthening of intensity of lipid peroxidation, which acquired the likely level of growth on the 60th and the 90th day of the experiment by increasing DC and MDA values by an average of 29,9 and 34,8 % and 50,3 and 28,0 % respectively relative to their control values.
In the blood of rats of experimental group the strengthening of intensity of lipid peroxidation was accompanied in the dynamics of research by an increase activity of catalase, which was gradual, and on the 30 -, 60 - and 90th day of the experiment, its percentage has averaged 25,3 %, 49,2 % and 42,6 % (p≤0,05) in accordance with its values relative to control animals.
It is known that the rapid decomposition and degradation of proteins may be caused by the formation of products of oxidative modifications that is just excessive formation of carbonyl derivatives is considered the primary marker of protein oxidation.
It was established that the maximum expression of prooxidant action of NcMe at a dose of 4,0 mg/kg body weight during long-term oral exposure in rats was established on the 30th day of the experiment, which was irreversible and preserved even in 30 days after cessation of mixtures of nanoparticles administration. The mechanism of prooxidant action NcMe was in the formation of oxidative stress in rats through an initial excess of toxic derivatives OMP within 15 days after the beginning of the experiment.
Thus, in blood plasma of rats in the absence of excessive formation of lipid peroxidation products there was determined growth of derivatives of neutral character on average on 22,3%, and derivatives of the main character – 41,6% (p≤0,05) respectively relative to their reference level.
In blood plasma of rats which were orally administered with the mixture of metal salts in the macro-and nanoparticle forms at a dose of 0,3 mg/kg body weight, likely changes of the intensity of OMP processes in terms of the formation of derivatives during the experiment were not registered. As a result of NcMe oral administration at a dose of 4,0 mg/kg body weight there was determined that the gradual reduction of lipid peroxidation products has been accompanied by spending antioxidant capacity resources by inhibition of catalase activity (from the 15th day of the experiment) by an average of 22,4% (p≤0,05) and total AOA (from the 30th day of the experiment) by 38,0% (p≤0,05) respectively relative to control values of these parameters. That is, based on the nature of intensity of OMP derivatives formation and content of lipid peroxidation products in the blood of rats at oral administration both a mixture of metal salts at a dose of 0,3 mg/kg body weight, and NcMe in the maximum dose (4,0 mg/kg body) there were not enough own resources of antioxidant capacity of the body of experimental animals to prevent exposure of active oxygen metabolites and appropriate inclusion of protective mechanisms.
But we can make a conclusion about the possible induction of antioxidant resources under the per oral NcMe actions at a dose of 0,3 mg/kg body weight for 30 days, that is illustrated by the increased activity of endogenous AOA on average by 15,6% (p≤0,05) relative to its control values, under the background of keeping the physiological levels of intensity of lipid and protein oxidation in the blood of experimental rats.
On the other hand, considering that the NcMe dose of 0,3 mg/kg body weight is biotic, in subsequent studies we consider it is necessar nutraceutical of adaptogenic orientation, to take into account these facts when creating nanocomposiite of adaptogenic orientation.
Key words: antioxidant sysyem, metal nanocomposite, oxidative modification of proteins, lipid peroxidation, metal salts, plasma, chronic toxicity, rats.
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