LUNG PROTECTIVE POTENTIAL EFFECT OF ZILEUTON DURING ENDOTOXAEMIA MODEL IN MALE MICE.

OBJECTIVE: The aim: This study was undertaken to investigatethe possible lung protective potential effect of zileuton during polymicrobial sepsis, through modulation of inflammatory and oxidative stress pathway. PATIENTS AND METHODS: Materials and methods: 24 adult male Swiss-albino mice aged 8-12 weeks, with a weight of 25-35g, were randomized into 4 equal groups n=6, sham (laparotomy without CLP), CLP (laparotomy with CLP), vehicle (equivalent volume of DMSO 1 hour prior to CLP), and Zileuton (5 mg/kg 1 hour prior to CLP) group. After 24 hrs. of sepsis, the lung tissue harvested and used to assess IL-6, IL-1B, IL-17, LTB-4,12(S) HETE and F2-isoprostane as well as histological examination. RESULTS: Results: Lung tissue inflammatory mediators IL-6, IL-1B, IL-17, LTB, 12 (S) HETE) and oxidative stress were carried out via ELISA. Lung tissue levels of IL-6, IL-1B, IL-17, LTB4, 12(S) HETE and oxidative stress (F2 isoprostan)level were significantly higher in sepsis group (p<0.05) as compared with sham group, while zileuton combination showed significant (p<0.05) lower level in these inflammatory mediators and oxidative stress as comparedto sepsis group. Histologically, All mice in sepsis group showed a significant (p<0.05) lung tissue injury, while in zileuton pretreated group showed significantly (p<0.05) reduced lung tissue injury. CONCLUSION: Conclusions: The results of the present study revealed that zileuton has the ability to attenuate lung dysfunction during CLP induced polymicrobial sepsis in male mice through their modulating effects on LTB4,12(S) HETE and oxidative stress downstream signaling pathways and subsequently decreased lungtissue levelsof proinflammatory cytokines (IL-1ß, and IL-6,IL-17).

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

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 pathways. 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-1ß, 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-1ß, IL-6, IL-17, LTB-4, and 12(S)HETE).