Inhaled Argon Impedes Hepatic Regeneration after Ischemia/Reperfusion Injury in Rats

• Published in: International journal of molecular sciences Vol. 21; no. 15; p. 5457
• Main Authors: Schmitz, Sophia M., Dohmeier, Henriette, Stoppe, Christian, Alizai, Patrick H., Schipper, Sandra, Neumann, Ulf P., Coburn, Mark, Ulmer, Tom F.
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30.07.2020; MDPI
• Subjects: Animals; Antibodies; Apoptosis - drug effects; Argon - pharmacology; Cell cycle; Gases; Gene Expression Regulation, Developmental - drug effects; Hepatocyte Growth Factor - genetics; Hepatocytes - drug effects; Histology; Humans; Interleukin-1beta - genetics; Interleukin-6 - genetics; Ischemia; Laboratory animals; Liver; Liver - drug effects; Liver - growth & development; Liver Regeneration - drug effects; Liver Regeneration - genetics; Rats; Reperfusion Injury - complications; Reperfusion Injury - pathology; Reperfusion Injury - therapy; Surgery; Tumor Necrosis Factor-alpha - genetics; Denmark; Germany; ischemia/reperfusion; interleukin 6; transplantation; argon; liver surgery; injury; liver regeneration
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21155457

Organoprotective effects of noble gases are subject of current research. One important field of interest is the effect of noble gases on hepatic regenerative capacity. For the noble gas argon, promising studies demonstrated remarkable experimental effects in neuronal and renal cells. The aim of this study was to investigate the effects of argon on the regenerative capacity of the liver after ischemia/reperfusion injury (IRI). Male, Sprague-Dawley rats underwent hepatic IRI by clamping of the hepatic artery. Expression of hepatoproliferative genes (HGF, IL-1β, IL-6, TNF), cell cycle markers (BrdU, TUNEL, Ki-67), and liver enzymes (ALT, AST, Bilirubin, LDH) were assessed 3, 36, and 96 h after IRI. Expression of IL-1β and IL-6 was significantly higher after argon inhalation after 36 h (IL-1β 5.0 vs. 8.7 fold, p = 0.001; IL-6 9.6 vs. 19.1 fold, p = 0.05). Ki-67 was higher in the control group compared to the argon group after 36 h (214.0 vs. 38.7 positive cells/1000 hepatocytes, p = 0.045). Serum levels of AST and ALT did not differ significantly between groups. Our data indicate that argon inhalation has detrimental effects on liver regeneration after IRI as measured by elevated levels of the proinflammatory cytokines IL-1β and IL-6 after 36 h. In line with these results, Ki-67 is decreased in the argon group, indicating a negative effect on liver regeneration in argon inhalation.