Abstract
Lidocaine, a common local anesthetic drug, has anti-inflammatory effects. It has demonstrated a protective effect in mice from septic peritonitis. However, it is unknown whether lidocaine has effects on high mobility group box 1 (HMGB1), a key mediator of inflammation. In this study, we investigated the effect of lidocaine treatment on serum HMGB1 level and HMGB1 expression in liver, lungs, kidneys, and ileum in septic rats induced by cecal ligation and puncture (CLP). We found that acute organ injury induced by CLP was mitigated by lidocaine treatment and organ function was significantly improved. The data also demonstrated that lidocaine treatment raised the survival of septic rats. Furthermore, lidocaine suppressed the level of serum HMGB1, the expression of HMGB1, and the activation of NF-κB p65 in liver, kidneys, lungs, and ileum. Taken together, these results suggest that lidocaine treatment exerts its protective effection on CLP-induced septic rats. The mechanism was relative to the inhibitory effect of lidocaine on the mRNA expression level of HMGB1 in multiple organs, release of HMGB1 to plasma, and activation of NF-κB.
Highlights
Sepsis, a systemic inflammatory response syndrome that complicates infection and injury, results in the excessive stimulation on the host immune system and the production of various proinflammatory cytokines
The activity of ileum diamine oxidase (DAO) significantly decreased in all groups subjected to cecal ligation and puncture (CLP) compared to the sham-operated group (P < 0.05)
The above results demonstrated that lidocaine inhibited High mobility group box 1 (HMGB1) mRNA expression in multiple organs of septic rats, so we investigate whether lidocaine affect the upstream signal transduction pathway of nuclear factor (NF)-κB as well
Summary
A systemic inflammatory response syndrome that complicates infection and injury, results in the excessive stimulation on the host immune system and the production of various proinflammatory cytokines. In addition to its nuclear expression, HMGB1 can be released from inflammatory cells and necrotic tissues during endotoxemia and sepsis [4]. The treatment with the delayed administration of antiHMGB1 antibodies [2, 3], a box of HMGB1 [3], and ethyl pyruvate [5] (an inhibitor of HMGB1) beginning as late as the disappearance of plasma TNF-α and IL-1β significantly increases survival. HMGB1 binds to cell surface receptors once released from the nucleus, and the nuclear factor (NF)-κB signaling pathway may be activated [6]. The therapeutic window for anti-HMGB1 therapies is significantly wider than that of TNF-α targeted interventions, and it may be possible to develop inhibitors of HMGB1 for the treatment of sepsis [1]
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