Cysteinyl-leukotriene Receptor Antagonist Montelukast Ameliorates Acute Lung Injury following Hemorrhagic Shock in Rats

FACP,; FRCS,; Doc, Post; FACS,; R. Hadi, Najah; Ghaly Yousif, Fadhil; Ph.D,; Mohsin Hashim, Ali; MSc,; FRCP,

	Cysteinyl-leukotriene Receptor Antagonist Montelukast Ameliorates Acute Lung Injury following Hemorrhagic Shock in Rats
KUFA MEDICAL JOURNAL
Article 1, Volume 14, Issue 1, 2011, Pages 135-145
Authors
; ; Post Doc; ; Najah R. Hadi; Fadhil Ghaly Yousif; ; Ali Mohsin Hashim; ;
Abstract
Acute lung injury following hemorrhagic shock/resuscitation is an important contributor to late morbidity and mortality in trauma patients. Hemorrhagic shock followed by resuscitation is considered as an insult frequently induces a systemic inflammatory response syndrome and oxidative stress that results in multiple-organ dysfunction syndrome including acute lung injury. Montelukast is a cysteinyl leukotriene receptor antagonist exerts an anti inflammatory and antioxidant activity. Objectives The objective of present study was to assess the possible protective effect of montelukast against hemorrhagic shock-induced acute lung injury via interfering with inflammatory and oxidative pathways. Materials and Methods Eighteen adult Albino rats were assigned to three groups each containing six rats: group I, sham group, rats underwent all surgical instrumentation but neither hemorrhagic shock nor resuscitation was done; group II, Rats underwent hemorrhagic shock (HS) for 1hr then resuscitated with Ringer’s lactate (1hr) (induced untreated group, HS); group III, HS + montelukast (7 mg/kg i.p. injection 30 min before the induction of HS, and the same dose was repeated just before reperfusion period). At the end of experiment (2 hr after completion of resuscitation), blood samples were collected for measurement of serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The lungs were harvested, excised and the left lung was homogenized for measurement of malondialdehyde (MDA) and reduced glutathione (GSH) and the right lung was fixed in 10% formalin for histological examination. Results Montelukast treatment significantly reduced the total lung injury score compared with the HS group (P < 0.05). Montelukast also significantly decreased serum TNF-α & IL-6; and lung MDA as compared with the HS group (P < 0.05). Montelukast treatment significantly prevented the decrease in the lung GSH levels compared with the HS group (P < 0.05). Conclusions The results of the present study reveal that montelukast may ameliorate lung injury in shocked rats via interfering with inflammatory and oxidative pathways implicating their role in the pathogenesis of hemorrhagic shock-induced lung inflammation.
Keywords
montelukast; hemorrhagic shock; acute lung injury; Oxidative stress; inflammatory markers

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