On the Mechanisms of the Cardiotoxic Effect of Lead Oxide Nanoparticles.

Lead compounds are one of the most common pollutants of the workplace air and the environment. In the occupational setting, the sources of their emission, including in nanoscale form, are various technological processes associated with lead smelting and handling of non-ferrous metals and their alloys, the production of copper and batteries. Both lead poisoning and lead exposure without obvious signs of poisoning have a detrimental effect on the cardiovascular system. The purpose of this research was to investigate the mechanisms of the cardiotoxic effect of lead oxide nanoparticles (PbO NPs). The toxicological experiment involved male albino rats subchronically exposed to PbO NPs (49.6 ± 16.0 nm in size) instilled intraperitoneally in a suspension. We then assessed post-exposure hematological and biochemical parameters of blood and urine, histological and ultrastructural changes in cardiomyocytes, and non-invasively recorded electrocardiograms and blood pressure parameters in the rodents. Myocardial contractility was studied on isolated preparations of cardiac muscles. We established that PbO NPs induced oxidative stress and damage to the ultrastructure of cardiomyocytes, and decreased efficiency of the contractile function of the myocardium and blood pressure parameters. We also revealed such specific changes in the organism of the exposed rats as anemia, hypoxia, and hypocalcemia.

Some data on the comparative and combined toxic activity of nanoparticles containing lead and cadmium with special attention to their vasotoxicity.

Moderate subchronic intoxication was induced in rats by repeated intraperitoneal injections of PbO (49.6 ± 16.0 nm) and/or CdO (57.0 ± 13.0 nm) nanoparticles (NP) three times a week during 6 weeks. In particular, there was a reduction in arterial blood pressure and in blood concentrations of a number of factors controlling vasoconstriction and vasodilation, particularly of endothelin 1 (ET-1). This toxic effect was attenuated with a bioprotective complex administered in the background. The study confirmed as well that the combined binary action typology varies depending on which effect it is estimated by.

Some outcomes and a hypothetical mechanism of combined lead and benzo(a)pyrene intoxication, and its alleviation with a complex of bioprotectors.

Rats were exposed 3 times a week during 6 weeks to repeated intraperitoneal injections of lead acetate solution in water (Pb) and/or benzo(а)pyrene solution in petrolatum oil (B(а)P) in various dose ratios. Towards the end of the period, the animals developed a moderate subchronic intoxication having some features characteristic of lead effects. The type of combined toxicity estimated with the help of isoboles constructed by the Response Surface Methodology was found to be varied depending on a particular effect, its level, and dose ratio. However, Pb and B(a)P in combination often displayed an additive or even superadditive action. In the group exposed to this combination compared with the group of rats exposed to B(a)P alone, its concentration in the organism was increased while the concentration of some B(a)P oxidative metabolism products was reduced. Such inhibition of B(a)P biotransformation, assumingly associated with impaired heme and, thus, cytochrome P450 synthesis induced by lead intoxication, can serve as an explanation for certain enhancement of the genotoxic effect of B(a)P. This effect was not present in the same combined intoxication if a complex of antitoxic bioprotectors was being administered in the background.

Further verification of some postulates of the combined toxicity theory: New animal experimental data on separate and joint adverse effects of lead and cadmium.

Outbred male rats were repeatedly injected intraperitoneally two-level sub-lethal doses of lead acetate and/or cadmium chloride solutions 3 times a week during 6 weeks. The animals developed explicit, even if moderate, subchronic intoxication characterized by a large number of indices, both common to both metals (including increased DNA fragmentation coefficient) and lead-specific. Special attention was paid to hemodynamic and electrocardiographic effects. The combined action of lead and cadmium was modeled with the help of the Response Surface Methodology to obtain additional support for the previously substantiated postulates of combined toxicity's typological ambiguity. This is dependent on which particular effect comes under consideration, on its level, and on the acting dose ratio. For one and the same toxic combination, the type of combined toxic action can vary from synergistic to contra-directional. In particular, the actions of lead and cadmium on blood pressure were found to be opposite in direction. Furthermore, it is shown once again that the systemic toxic effects of a metal combination, its in vivo genotoxicity included, can be more or less attenuated by background administration of a theoretically justified composition of biologically active agents.