Argon Attenuates Multiorgan Failure in Relation with HMGB1 Inhibition

Int J Mol Sci. 2021 Mar 23;22(6):3257. doi: 10.3390/ijms22063257.


Argon inhalation attenuates multiorgan failure (MOF) after experimental ischemic injury. We hypothesized that this protection could involve decreased High Mobility Group Box 1 (HMGB1) systemic release. We investigated this issue in an animal model of MOF induced by aortic cross-clamping. Anesthetized rabbits were submitted to supra-coeliac aortic cross-clamping for 30 min, followed by 300 min of reperfusion. They were randomly divided into three groups (n = 7/group). The Control group inhaled nitrogen (70%) and oxygen (30%). The Argon group was exposed to a mixture of argon (70%) and oxygen (30%). The last group inhaled nitrogen/oxygen (70/30%) with an administration of the HMGB1 inhibitor glycyrrhizin (4 mg/kg i.v.) 5 min before aortic unclamping. At the end of follow-up, cardiac output was significantly higher in Argon and Glycyrrhizin vs. Control (60 ± 4 and 49 ± 4 vs. 33 ± 8 mL/kg/min, respectively). Metabolic acidosis was attenuated in Argon and Glycyrrhizin vs. Control, along with reduced amount of norepinephrine to reverse arterial hypotension. This was associated with reduced interleukin-6 and HMGB1 plasma concentration in Argon and Glycyrrhizin vs. Control. End-organ damages were also attenuated in the liver and kidney in Argon and Glycyrrhizin vs. Control, respectively. Argon inhalation reduced HMGB1 blood level after experimental aortic cross-clamping and provided similar benefits to direct HMGB1 inhibition.

Keywords: High Mobility Group Box 1 (HMGB1); argon; inflammation; ischemia-reperfusion; multiorgan failure.

MeSH terms

  • Animals
  • Argon / pharmacology*
  • Biopsy
  • Blood Pressure / drug effects
  • Cardiac Output / drug effects
  • Cytokines / blood
  • Disease Models, Animal
  • HMGB1 Protein / antagonists & inhibitors*
  • Heart Function Tests
  • Hemodynamics / drug effects
  • Immunohistochemistry
  • Male
  • Multiple Organ Failure / diagnosis
  • Multiple Organ Failure / drug therapy*
  • Multiple Organ Failure / etiology
  • Multiple Organ Failure / metabolism*
  • Rabbits


  • Cytokines
  • HMGB1 Protein
  • Argon