编号 3 (2015)

For the first time an investigation was conducted into the influence of sarin (GB), soman (GD) and Russian substance Vx (RVX) with and without application of antidotal preparations ( carboxin and carboxin mixed with atropine) on the qualitative and quantitative composition of free and etherified fatty acids at the level of ½LD₅₀ (FFA and EFA correspondingly) in the blood plasma. Administration of GB and GD doses at the level of ½LD₅₀ to rats causes a decrease of FFA in blood plasma after 3 hours. 24 hours later the FFA returns to the normal level. Administration of 2x0.4 LD50 RVX conditions an elevated level of FFA and EFA in the blood plasma throughout a week including enrichment of the FFA fraction with polyunsaturated acids. Antidotal therapy normalizes the FFA and EFA dynamics but does not prevent changes in their levels over first hours. Unlike organophosphorous pesticides, RVX at the level of ½LD₅₀ inhibits acetyl cholinesterase but does not affect lipid exchange over first 24 hours.

The therapeutic action of atropine (0.4, 2, 20 mg/kg) was assessed on models of rats intramuscular and intragastric poisoning with malathion in a dose of 1 LD50. It was demonstrated that the drug prevented animals death after the intramuscular administration of malathion and promoted the reduction of intensity of a cholinopositive symptomatology. It also promoted the recovery of the acetyl cholinesterase activity in rats blood up to 80% 8 hours after the therapy, and 24 hours after the injection of malathion, this index reached levels in the control group. The preparation had no protective effect on the modelled intragastric poisoning by malathion independently of its dose. In animals to which atropine (2mg/kg) was administrated an hour after intoxication, the enzyme activity in blood was 40% while in the control group it was 80%. It is practicable to take these findings into consideration while searching and selecting efficient medications for emergency treatment of organophosphorous intoxications.

The paper summarizes main results of the authors’ in vivo toxicological experiments on rats exposed to either a single intratracheal instillation or to repeated intraperitoneal injections of nanoparticles (NP) of silver, gold, iron oxide, copper oxide, nickel oxide and manganese oxide in stable water suspensions without any chemical additives.

It was found out that these NPs were much more noxious on both cellular and organ- systemic levels as compared to their own micrometric or even submicron counterparts. However, the dependence of organ-systemic toxicity on particle sizes within the nanometer range is intricate and non-unique due to complex and often contra-directional relationships between the intrinsic biological aggressiveness of specific nanoparticles, on the one hand, and complex mechanisms governing their toxicokinetics, on the other.

Our data testify to a high activity of the pulmonary phagocytosis of nanoparticles deposited in airways. This fact suggests that safe levels of exposure to airborne nanoparticles are possible in principle. An approach is considered to establish provisional standards for such an exposure based on about 10-15-fold decreased exposure as compared to limits which are officially set for respective micro-scale industrial aerosols.

It was shown that against the background of adequately composed combinations of some bioactive agents (comprising pectin, multivitamin-multimineral preparations, some amino acids, and omega-3 PUFA) , the systemic toxicity and genotoxicity of metallic NPs could be markedly attenuated.