Lidocaine protects against renal and hepatic dysfunction in septic rats via downregulation of Toll-like receptor 4

Abstract

The present study was designed to determine the renoprotective and hepatoprotective effect of lidocaine in septic rats through the Toll‑like receptor 4 (TLR4) signaling pathway. Adult male Sprague‑Dawley rats were randomly divided into the following three groups: control, sepsis model and 10% lidocaine. A model of sepsis was established by injection of lipopolysaccharide (LPS; 5 mg/kg) into the intraperitoneal cavity of rats. The same volume of saline was injected intraperitoneally into rats of the control group instead of LPS. Light microscopy was used to observe structural changes of the hepatic and nephridial tissues. qPCR was used to measure TLR4 mRNA expression levels and the protein expression was detected by flow cytometry. Western blotting was used to measure myocardial nuclear factor κB (NF‑κB) protein levels and ELISA was used to measure the levels of interleukin‑6 (IL‑6) in hepatic and nephridial tissues. The results demonstrated that 10% lidocaine treatment markedly decreased hepatic and nephridial injury in septic rats and inhibited the expression levels of TLR4, NF‑κB and IL‑6, which were upregulated in the sepsis model. In addition, the results indicated that lidocaine protects against renal and hepatic dysfunction in septic rats, which may be mediated by the downregulation of TLR4 and associated signaling molecules and inhibition of the inflammatory response.

Hyaluronan suppresses lidocaine-induced apoptosis of human chondrocytes in vitro by inhibiting the p53-dependent mitochondrial apoptotic pathway

“…www.nature.com/aps Lee YJ et al Acta Pharmacologica Sinica npg inducing activity of lidocaine was not the focus of this study, other signaling pathway(s), including Akt [26] , NF-κB [27] , and the activation of both extrinsic and intrinsic apoptosis pathways [28] may also contribute to the lidocaine-induced chondrotoxicity. We cannot rule out whether lidocaine regulates these signaling pathways in the experimental conditions of this study; nevertheless, it can be postulated that lidocaine induces apoptosis by causing an increased ratio of Bax to Bcl-2.…”

Profile of HMGB1 mRNA Expression and TLR4 Protein in BALB/c Mice Model Sterile Injury after Systemic Lidocaine Administration

“…18 In a separate study, Liu J et al have shows that systemic lidocaine therapy protects dysfunction of kidney and liver in septic mice model with inhibiting expression of TLR4, NF-κβ and interleukin-6. 19 While the expression of HMGB1 mRNA and TLR4 protein levels in the control group increased steadily when compared from before the injury, 4 h after injury, and 2 h after administration of distilled water, p < 0.00. The results of this study show that administration of distilled water does not provide a therapeutic efficacy to inhibit inflammatory process.…”

Small-Volume Adenosine, Lidocaine, and Mg 2+ 4-Hour Infusion Leads to 88% Survival after 6 Days of Experimental Sepsis in the Rat without Antibiotics

“…Similarly, Wang and colleagues showed that lidocaine was protective against sepsis in rats and is linked to inhibition of serum high-mobility-group box 1 (HMGB1) expression and NF-B in liver, kidneys, lungs, and ileum (47). Liu and colleagues also showed that lidocaine protected against renal and hepatic dysfunction in septic rats from the downregulation of Toll-like receptor 4 (48). It is noteworthy that in all of our previous work, from myocardial ischemia to hemorrhagic shock, the ALM combination is key for whole-body protection, as the individual adenosine or lidocaine groups provided suboptimal outcomes (16).…”