Lidocaine attenuates lipopolysaccharide-induced acute lung injury through inhibiting NF-kappaB activation.
OBJECTIVE
Lidocaine has been reported to attenuate the inflammatory response in addition to its anesthetic activity, but the mechanisms are poorly understood. The objective of this study is to determine if lidocaine prior to endotoxemia diminishes pulmonary dysfunction by blocking the NF-kappaB activation.


METHODS
Rats were assigned to: (1) control (0.9% sodium chloride); (2) lipopolysaccharides (LPS); (3) LPS + lidocaine 1 mg/kg; (4) LPS + lidocaine 2 mg/kg, and (5) LPS + lidocaine 4 mg/kg. The LPS and LPS + lidocaine 4 mg/kg groups were subjected to 1-, 3-, 6- and 12-hour time points. To investigate the activation of NF-kappaB, the expression of NF-kappaB in the nuclear and I kappaB alpha in the cytosol extracts were analyzed by Western blot. The concentration of TNF-alpha and IL-6 in serum was detected by ELISA. The pathologic changes of the lung were observed using HE staining.


RESULTS
After i.p. injection of LPS, the expression of NF-kappaB in the nuclear extracts was significantly increased and I kappaB alpha in the cytosol extracts was markedly decreased. The concentration of TNF-alpha and IL-6 in serum was increased. Pathological examination showed that the normal structure of the lung was destroyed badly. However, lidocaine reversed the above results.


CONCLUSIONS
Lidocaine attenuates LPS-induced lung injury via mechanisms involving inhibiting NF-kappaB activation and cytokine release, which implies that lidocaine may be a potential anti-inflammatory agent in endotoxemia.
Feng
Guang
G
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, PR China.
Liu
Su
S
Wang
Guang-Lei
GL
Liu
Gong-Jian
GJ
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015153:Blotting, Western; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*