| Autor: |
Varlamova EG; Institute of Cell Biophysics, the Russian Academy of Sciences, Federal Research Center 'Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences', 142290 Pushchino, Russia., Goltyaev MV; Institute of Cell Biophysics, the Russian Academy of Sciences, Federal Research Center 'Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences', 142290 Pushchino, Russia., Rogachev VV; Institute of Cell Biophysics, the Russian Academy of Sciences, Federal Research Center 'Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences', 142290 Pushchino, Russia., Gudkov SV; Prokhorov General Physics Institute, the Russian Academy of Sciences, 119991 Moscow, Russia.; Department of Biophysics, Lobachevsky State University of Nizhny Novgorod, 603022 Nizhny Novgorod, Russia., Karaduleva EV; Institute of Cell Biophysics, the Russian Academy of Sciences, Federal Research Center 'Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences', 142290 Pushchino, Russia., Turovsky EA; Institute of Cell Biophysics, the Russian Academy of Sciences, Federal Research Center 'Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences', 142290 Pushchino, Russia. |
| Abstrakt: |
For the first time, based on the expression analysis of a wide range of pro- and anti-fibrotic, pro- and anti-inflammatory, and pro- and anti-apoptotic genes, key markers of endoplasmic reticulum stress (ER-stress), molecular mechanisms for the regulation of fibrosis, and accompanying negative processes caused by thioacetamide (TAA) injections and subsequent injections of selenium-containing nanoparticles and sorafenib have been proposed. We found that selenium nanoparticles of two types (doped with and without sorafenib) led to a significant decrease in almost all pro-fibrotic and pro-inflammatory genes. Sorafenib injections also reduced mRNA expression of pro-fibrotic and pro-inflammatory genes but less effectively than both types of nanoparticles. In addition, it was shown for the first time that TAA can be an inducer of ER-stress, most likely activating the IRE1α and PERK signaling pathways of the UPR, an inducer of apoptosis and pyroptosis. Sorafenib, despite a pronounced anti-apoptotic effect, still did not reduce the expression of caspase-3 and 12 or mitogen-activated kinase JNK1 to control values, which increases the risk of persistent apoptosis in liver cells. After injections of selenium-containing nanoparticles, the negative effects caused by TAA were leveled, causing an adaptive UPR signaling response through activation of the PERK signaling pathway. The advantages of selenium-containing nanoparticles over sorafenib, established in this work, once again emphasize the unique properties of this microelement and serve as an important factor for the further introduction of drugs based on it into clinical practice. |
