Some Peculiarities in the Dose Dependence of Separate and Combined In Vitro Cardiotoxicity Effects Induced by CdS and PbS Nanoparticles With Special Attention to Hormesis Manifestations

Abstract

Spherical nanoparticles (NPs) of cadmium and lead sulfides (diameter 37 ± 5 and 24 ± 4 nm, respectively) have been found to be cytotoxic for HL-1 cardiomyocytes as evidenced by decrease in adenosine triphosphate–dependent luminescence. Cadmium sulfide (CdS)-NPs were discovered to produce a much greater cytotoxic impact than lead sulphide (PbS)-NP. Given the same dose range, CdS-NP reduced the number of calcium spikes. A similar effect was observed for small doses of PbS-NP. In addition to cell hypertrophy under the impact of certain doses of CdS-NP and PbS-NP, doses causing cardiomyocyte size reduction were identified. For these 3 outcomes, we obtained both monotonic “dose–response” functions (well approximated by the hyperbolic function) and different variants of non-monotonic ones for which we found adequate mathematical expressions by modifying certain models of hormesis available in the literature. Data analysis using a response surface linear model with a cross-term provided new support to the previously established postulate that a diversity of types of joint action characteristic of one and the same pair of damaging agents is one of the important assertions of the general theory of combined toxicity.

Comparative and Combined In Vitro Vasotoxicity of Nanoparticles Containing Lead and Cadmium

“…Moreover, within the dose ranges used, this dependence is bi- or tri-phasic for some of the indices. This required approximating it by more complex expressions than the usual models of hormesis (see (Panov et al 2020 9 and articles cited therein). Since polyphase functions describe a complex and multifactorial biological phenomenon, it would be unlikely to expect that such a dose-response dependence could be adequately expressed by simple functions.…”

“…Since polyphase functions describe a complex and multifactorial biological phenomenon, it would be unlikely to expect that such a dose-response dependence could be adequately expressed by simple functions. For instance, in 9 this dependence is represented by power functions depending on 8 parameters.…”

“…That is why, the effects of various NP combinations were the focus of a range of comparative experimental and mathematical modeling studies carried out by our research team, including the nanotoxicology of Ni and Mn 5 , 6 ; Cu, Zn, Pb 7 ; Al, Ti and Si, 8 and Pb and Cd 9 combined in various proportions. Pikula et al, 2020 10 experimented with CdS and ZnS combination.…”

“…In the foregoing, the occupational and environmental hazards of metal-containing nanoparticles for humans were mentioned as important in practical terms, and so the toxic properties of lead and, to a lesser extent, cadmium have been considered in a number of experimental studies, particularly by our team. 7 , 9 , 20 , 21 However, little attention (if any) has been given just to the vaso-cardiotoxicity of such nanoparticles.…”

“…As far as we know, the in vitro cardiotoxicity of lead and cadmium has been studied only by our team in experiments on HL-1 cardiomyocytes. 9 Judging by decreased adenosine triphosphate–dependent luminescence, cadmium sulfide nanoparticles (CdS-NP) produced a considerably greater cytotoxic effect than lead sulfide ones (PbS-NP). However, in the same dose range, CdS-NP caused fewer calcium spikes whereas PbS-NP produced a similar effect at lower doses.…”