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

• Published in: Molecular medicine reports Vol. 9; no. 1; pp. 118 - 124
• Main Authors: LIU, JINBO, ZHANG, HAOHUA, QI, ZONGCAI, ZHENG, XIUYING
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.01.2014; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Animals; Cytokines; Disease Models, Animal; Dosage and administration; Down-Regulation; Enzyme-linked immunosorbent assay; Flow cytometry; Gene expression; Health aspects; Inflammation; Interleukin 6; Interleukin-6 - metabolism; Kidney - drug effects; Kidney - metabolism; Kidney - physiopathology; Kidney diseases; Kidneys; Laboratory animals; Lidocaine; Lidocaine - pharmacology; lipopolysaccharide; Lipopolysaccharides; Lipopolysaccharides - toxicity; Liver; Liver - drug effects; Liver - metabolism; Liver - physiopathology; Liver diseases; Male; Mortality; Neutrophils; NF-kappa B - metabolism; Prevention; Protective Agents - pharmacology; Rats; Rats, Sprague-Dawley; Renal function; RNA, Messenger - metabolism; Rodents; Sepsis; Sepsis - etiology; Sepsis - pathology; Signal transduction; Studies; systemic inflammatory response syndrome; TLR4; TLR4 protein; Toll like receptor 4; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Tumor necrosis factor-TNF; Western blotting
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2013.1799

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.