Antifibrotic Effect of Selenium-Containing Nanoparticles on a Model of TAA-Induced Liver Fibrosis

• Published in: Cells (Basel, Switzerland) Switzerland), 2023-11, Vol.12 (23), p.2723
• Main Authors: Varlamova, Elena G, Goltyaev, Michail Victorovich, Rogachev, Vladimir Vladimirovich, Gudkov, Sergey V, Karaduleva, Elena V, Turovsky, Egor A
• Format: Article
• Language: English
• Subjects: Acids; Anti-inflammatory drugs; Antibodies; Apoptosis; Care and treatment; Caspase-3; Diagnosis; Dosage and administration; Endoplasmic reticulum; Endoribonucleases - metabolism; Fibrosis; Gene expression; Health aspects; Hepatocytes; Humans; Inflammation; Laboratory animals; Lasers; Liver; Liver cancer; Liver Cirrhosis - chemically induced; Liver Cirrhosis - drug therapy; liver fibrosis; Molecular modelling; Nanoparticles; Properties; Protein Serine-Threonine Kinases - metabolism; Pyroptosis; Radiation; Selenium; Selenium - pharmacology; Selenium - therapeutic use; selenium nanoparticles; Signal transduction; sorafenib; Sorafenib - pharmacology; Sorafenib - therapeutic use; Thioacetamide; Thioacetamide - adverse effects
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells12232723

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.