The anti-inflammatory and antioxidant effects of Montelukast on lung sepsis in adult mice

Abstract

One of the most complex clinical challenges facing medical practice is sepsis-induced lung dysfunction resulting from polymicrobial sepsis. Although many therapeutic approaches have been used in such clinical challenges, there is still further need for a new effective therapeutic approach. The objective of this study was to investigate if Montelukast could protect the lungs during polymicrobial sepsis by regulating inflammatory markers and the oxidative stress path-ways. Twenty-four mature male Swiss-albino mice aged 8–12 weeks, with a weight of 20–30 g, were randomized into 4 equal groups (n=6), sham (laparotomy without cecal ligation and puncture (CLP)), CLP (laparotomy with CLP), vehicle 1 (equivalent volume of DMSO 1 hour prior to CLP), Montelukast (10 mg/kg IP 1 hour prior to CLP). Lung tissue pro-inflammatory mediators IL-6, IL-1β, IL-17, LTB-4 12(S) HETE, and oxidative stress were assessed using ELISA. The levels of F2 isoprostane were considerably greater in the sepsis group (p<0.05) as compared to the sham group, while Montelukast was significantly lower (p<0.05) in these inflammatory mediators and oxidative stress as compared to the sepsis group. Histologically, the lung tissue damage was significant (p<0.05) in all mice in the sepsis group, while Montelukast significantly reduced lung tissue injury (p<0.05). The current findings indicated that Montelukast could attenuate lung dysfunction during CLP-induced polymicrobial sepsis in male mice through their modulating effects on pro-inflammatory and oxidative stress downstream signalling pathways and subsequently decrease lung tissue cytokine concentrations (IL-1β, IL-6, IL-17, LTB-4, and 12(S)HETE).