The various dose-dependent effect of selenium oxide and copper oxide nanoparticles in vitro and application of the hormesis paradigm

Introduction. In vitro studies on a culture of cardiomyocytes have shown that dose-response relationships could be monotonic for some effects and non-monotonic for others. In this work, we wanted to demonstrate that these features of the dose-response relationship are a general pattern. Materials and methods. In vitro experiments were conducted on the culture of human fibroblast-like cells FLECH-104. The cytotoxicity of spherical nanoparticles of selenium oxide (SeO-NP) and copper oxide (CuO-NP) was studied with an average diameter of 51 ± 14 nm and 21 ± 4 nm, respectively. Results. SeO-NP and CuO-NP were cytotoxic for human fibroblast-like cells, as judged by a decrease in ATP-dependent luminescence. In this case, the cytotoxicity of CuO-NP was somewhat more substantial than the SeO-NP one. Our experiment revealed doses that cause both cell hypertrophy and a decrease in the size of cells and nuclei. Discussion. We observed both monotonic and different variants of the non-monotonic dose-response relationship. For the latter, it was possible to construct adequate mathematical expressions based on the generalized hormesis paradigm that we had considered earlier concerning the CdS-NP and PbS-NP cytotoxicity for cardiomyocytes. Conclusion. The general rule is the variability of the dose-response dependence types manifested in different cytotoxic effects of nanoparticles.

A Geant4-DNA Evaluation of Radiation-Induced DNA Damage on a Human Fibroblast

Accurately modeling the radiobiological mechanisms responsible for the induction of DNA damage remains a major scientific challenge, particularly for understanding the effects of low doses of ionizing radiation on living beings, such as the induction of carcinogenesis. A computational approach based on the Monte Carlo technique to simulate track structures in a biological medium is currently the most reliable method for calculating the early effects induced by ionizing radiation on DNA, the primary cellular target of such effects. The Geant4-DNA Monte Carlo toolkit can simulate not only the physical, but also the physico-chemical and chemical stages of water radiolysis. These stages can be combined with simplified geometric models of biological targets, such as DNA, to assess direct and indirect early DNA damage. In this study, DNA damage induced in a human fibroblast cell was evaluated using Geant4-DNA as a function of incident particle type (gammas, protons, and alphas) and energy. The resulting double-strand break yields as a function of linear energy transfer closely reproduced recent experimental data. Other quantities, such as fragment length distribution, scavengeable damage fraction, and time evolution of damage within an analytical repair model also supported the plausibility of predicting DNA damage using Geant4-DNA.The complete simulation chain application “molecularDNA”, an example for users of Geant4-DNA, will soon be distributed through Geant4.

Cell-Penetrating Delivery of Nitric Oxide by Biocompatible Dinitrosyl Iron Complex and Its Dermato-Physiological Implications

After the discovery of endogenous dinitrosyl iron complexes (DNICs) as a potential biological equivalent of nitric oxide (NO), bioinorganic engineering of [Fe(NO)2] unit has emerged to develop biomimetic DNICs [(NO)2Fe(L)2] as a chemical biology tool for controlled delivery of NO. For example, water-soluble DNIC [Fe2(μ-SCH2CH2OH)2(NO)4] (DNIC-1) was explored for oral delivery of NO to the brain and for the activation of hippocampal neurogenesis. However, the kinetics and mechanism for cellular uptake and intracellular release of NO, as well as the biocompatibility of synthetic DNICs, remain elusive. Prompted by the potential application of NO to dermato-physiological regulations, in this study, cellular uptake and intracellular delivery of DNIC [Fe2(μ-SCH2CH2COOH)2(NO)4] (DNIC-2) and its regulatory effect/biocompatibility toward epidermal cells were investigated. Upon the treatment of DNIC-2 to human fibroblast cells, cellular uptake of DNIC-2 followed by transformation into protein-bound DNICs occur to trigger the intracellular release of NO with a half-life of 1.8 ± 0.2 h. As opposed to the burst release of extracellular NO from diethylamine NONOate (DEANO), the cell-penetrating nature of DNIC-2 rationalizes its overwhelming efficacy for intracellular delivery of NO. Moreover, NO-delivery DNIC-2 can regulate cell proliferation, accelerate wound healing, and enhance the deposition of collagen in human fibroblast cells. Based on the in vitro and in vivo biocompatibility evaluation, biocompatible DNIC-2 holds the potential to be a novel active ingredient for skincare products.