Glycyrrhizin ameliorating sterile inflammation induced by low-dose radiation exposure

Abstract

Glycyrrhizin (GL) is a direct inhibitor of HMGB1 which acts as an alarmin when excreted into the extracellular space. High-dose radiation in radiotherapy induces collateral damage to the normal tissue, which can be mitigated by GL inhibiting HMGB1. The purpose of this study was to assess changes in HMGB1 and pro-inflammatory cytokines and to evaluate the protective effect of GL after low-dose radiation exposure. BALB/c mice were irradiated with 0.1 Gy (n = 10) and 1 Gy (n = 10) with GL being administered to half of the mice (n = 5, respectively) before irradiation. Blood and spleen samples were harvested and assessed for oxidative stress, HMGB1, pro-inflammatory cytokines, and cell viability. HMGB1 and pro-inflammatory cytokines increased and cell viability decreased after irradiation in a dose-dependent manner. Oxidative stress also increased after irradiation, but did not differ between 0.1 Gy and 1 Gy. With the pretreatment of GL, oxidative stress, HMGB1, and all of the pro-inflammatory cytokines decreased while cell viability was preserved. Our findings indicate that even low-dose radiation can induce sterile inflammation by increasing serum HMGB1 and pro-inflammatory cytokines and that GL can ameliorate the sterile inflammatory process by inhibiting HMGB1 to preserve cell viability.

DAMPs and radiation injury

“…In acute lung injury and hepatic ischemia-reperfusion injury models, administration of anti-HMGB1 antibody reduces lung neutrophil influx and pulmonary edema and mitigates liver damage ( 67 , 68 ). Exposure to ionizing radiation increases in both cellular mRNA expression and serum protein levels of HMGB1 in a dose-dependent manner in experimental mice model ( 69 ). Glycyrrhizin, one of the inhibitors of HMGB1, reduced the release of serum inflammatory cytokines in abdominal irradiated mice (6.5 Gy) through the downregulation of the HMGB1/TLR4 signaling pathway and significantly attenuated intestinal injury ( 50 ).…”

Protective role of ethyl pyruvate in spinal cord injury by inhibiting the high mobility group box-1/toll-like receptor4/nuclear factor-kappa B signaling pathway

“…The high mobility group box-1/toll-like receptor4/nuclear factor-kappa B signaling pathway HMGB1, as a protein of the 215 amino acids, is located in a stable environment of the nucleus. In healthy cells, HMGB1 plays a non-histone role in the nucleus that is key to maintain the nucleosome stability and DNA transcription (Kim et al, 2021). HMGB1 can be secreted via two ways: One is actively secreted by the immune system as a warning signal during cell stress; the other is aggressively secreted by the necrotic cells (Manivannan et al, 2020).…”

Natural Products of Licorice for Uranium Decorporation with Low Toxicity and High Efficiency

“…37 Kim et al have reported that pretreatment with glycyrrhizic acid can effectively alleviate radiation damage and oxidative stress and improve cell survival rates in mice exposed to low-dose radiation. 38 Therefore, licorice and GL can reduce radiation damage by regulating immunity, relieving inflammation, and eliminating oxidants.…”

“…Chen et al demonstrated that glycyrrhizic acid can effectively alleviate the multiorgan inflammatory response caused by radiation injury of mice skin, and achieve the effect of radiation therapy and protection . Kim et al have reported that pretreatment with glycyrrhizic acid can effectively alleviate radiation damage and oxidative stress and improve cell survival rates in mice exposed to low-dose radiation . Therefore, licorice and GL can reduce radiation damage by regulating immunity, relieving inflammation, and eliminating oxidants.…”