Glibenclamide Pretreatment Attenuates Acute Lung Injury by Inhibiting the Inflammatory Responses and Oxidative Stress in a Polymicrobial Sepsis Animal Model

Abstract

Background: Emerging evidence suggests that the NLRP3 inflammasome pathway and its downstream cytokines play key roles in the pathophysiology of inflammatory diseases. Glibenclamide is a widely used sulfonylurea drug for the treatment of type 2 diabetes, which has been reported to inhibit the activation of NLRP3 inflammasome. However, the role of glibenclamide on acute lung injury (ALI) is not known in a mouse model induced by cecal ligation and perforation (CLP). Methods: Thirty mice were equally assigned to the Sham group, CLP group, and CLP+glibenclamide groups (N=10). One hour before CLP or sham operation, mice received an intraperitoneal injection of 50 mg/kg glibenclamide or the same volume of normal saline. Interleukin (IL)-1β, IL-6, IL-18, tumor necrosis factor (TNF)-α, Toll-like receptor 4, inducible nitric oxide synthase, caspase-1, nitric oxide, wet-to-dry weight ratio, malondialdehyde, and superoxide dismutase in the lung were assessed at 24 hours after the operation. The 7-day survival rate was also recorded.Results: Glibenclamide pretreatment alleviated ALI, as indicated by decreased neutrophil infiltration and wet-to-dry weight ratio, which was accompanied by the decreased levels of interleukin (IL)-1β, IL-6, Toll-like receptor 4, inducible nitric oxide synthase, caspase-1, nitric oxide, and malondialdehyde in the lung. Furthermore, glibenclamide pretreatment prevented the sepsis-induced hyperglycemia at 6 hours after CLP. However, no significant difference was detected in pulmonary levels of nuclear factor (NF)-κB p65, TNF-α, IL-18, and superoxide dismutase or the 7-day survival rate between the CLP group and the CLP + glibenclamide group. Conclusions: Glibenclamide pretreatment attenuates the ALI by inhibiting the inflammatory responses and oxidative stress in a polymicrobial sepsis animal model. Citation: Mu- Huo Ji, Jiao- Jiao Yang, Lin- Sha Ju, Si- Hai Zhu, Jian- Jun Yang. Glibenclamide pretreatment attenuates acute lung injury by inhibiting the inflammatory responses and oxidative stress in a polymicrobial sepsis animal model. J Anesth Perioper Med 2014; 1: 36-43. doi: 10.24015/JAPM.2014.0006This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.