Home FOR AUTHORS General Physiology and Biophysics 2024 General Physiology and Biophysics Vol.43, No.5, p, 469–484, 2024

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General Physiology and Biophysics Vol.43, No.5, p, 469–484, 2024

Title: Cytotoxic and pro-oxidant profile of a photosensitive ruthenium nitrosyl candidate for NO delivery in healthy human fibroblasts
Author: Hande Özbaşak, Hani M. Elbeheiry, Martin Schulz, Lucia Račková
Abstract: Ruthenium nitrosyl (Ru-NO) complexes are of interest as photoactive nitric oxide (NO) donor candidates for local therapeutic applications. NO plays a crucial regulatory role in skin homeostasis, concentration-dependently affecting processes like the proliferation, apoptosis, autophagy and redox balance. In this context, we investigated HE-10, a ruthenium-based photoinducible NO donor, for its pro-oxidant and cytotoxic effects under light and dark conditions in VH10 human foreskin fibroblast cells. We also tested its intracellular and extracellular NO-releasing function. Our study reveals a significant dose-dependent cytotoxic effect of HE-10, an increase in intracellular reactive oxygen and nitrogen species, and the occurrence of apoptosis in skin fibroblast cells. Furthermore, exposure to both increasing doses of HE-10 and white LED light led to substantial cellular events, including a significant induction of autophagy and G2/M phase cell cycle arrest. Paradoxically, these effects were not solely attributable to NO release based on DAF2-DA NO probe results, suggesting that intracellular photochemical reactions additional to NO photolysis contribute to HE-10’s biological activity. This study shows that HE-10 exhibits both cytotoxic and potential therapeutic effects, depending on concentration and light exposure. These findings are crucial for developing targeted Ru-NO complex treatments for skin diseases and potentially certain types of skin cancer, where controlled NO release could be beneficial.
Keywords: Photosensitive nitric oxide donor — Ruthenium nitrosyl complex — Cytotoxicity — Oxidative stress — Skin fibroblasts
Published online: 16-Aug-2024
Year: 2024, Volume: 43, Issue: 5 Page From: 469, Page To: 484
doi:10.4149/gpb_2024031


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