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Front. Pharmacol. | doi: 10.3389/fphar.2019.01277

Cytoprotective Effects of Dinitrosyl Iron Complexes on Viability of Human Fibroblasts and Cardiomyocytes.

 Natalia P. Akentieva1*, Natalia A. Sanina1, 2, Artur R. Gizatullin1, Natalia I. Shkondina1, Tatyana R. Prikhodchenko1, Stanislav I. Shram3,  Nikolai Zhelev4 and Sergei M. Aldoshin1
  • 1Institute of Problems of Chemical Physics (RAS), Russia
  • 2Lomonosov Moscow State University, Russia
  • 3Institute of Molecular Genetics (RAS), Russia
  • 4University of Dundee, United Kingdom

Nitric oxide (NO) is a significant signalling molecule, which plays a pivotal role in maintaining vascular homeostasis. Dinitrosyl iron complexes (DNICs, donors NO) are widely used in the treatment of cardiovascular disease. However, the role of DNICs in metabolic processes of cell, their protective properties in doxorubicin-induced toxicity remain to be clarified. Here, we found that novel class of mononuclear DNICs with functional sulfur-containing ligands enhanced the cell viability of human lung fibroblasts and cardiomyocytes. Moreover, DNICS demonstrated remarkable protection against doxorubicin-induced toxicity in fibroblasts and in H9c2 cells. Data revealed that the DNICs compounds modulate the mitochondria function by decreasing the mitochondrial membrane potential (ΔΨm). Results of flow cytometry showed that DNICs were not affected the proliferation, growth of fibroblasts. Moreover, this study revealed that DNICs were not affected on the level of glutathione and reactive oxygen species in cells. In addition the results indicated that DNICs maintained the ATP equilibrium in cells. Taken together, these findings show that DNICs have protective properties in vitro. It was further suggested that DNICs may be uncouplers of oxidative phosphorylation in mitochondria and protective mechanism is mainly provided by the leakage of excess charge through the mitochondrial membrane. It is assumed that the DNICs have the therapeutic potential for treating cardiovascular diseases and for decreasing of chemotherapy-induced cardiotoxicity in cancer survivors.

Keywords: DNICs, Donors NO, Heart disease, Cell viability, membrane potential

Received: 11 Jul 2019; Accepted: 07 Oct 2019.

Copyright: © 2019 Akentieva, Sanina, Gizatullin, Shkondina, Prikhodchenko, Shram, Zhelev and Aldoshin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Natalia P. Akentieva, Institute of Problems of Chemical Physics (RAS), Chernogolovka, Russia, na_aken@icp.ac.ru