Cysteinyl leukotriene receptor antagonist montelukast ameliorates acute lung injury following haemorrhagic shock in rats

Abstract

Objectives: The aim of this study was to assess the possible protective effect of montelukast against haemorrhagic shock-induced acute lung injury by interfering with inflammatory and oxidative pathways. Acute lung injury following haemorrhagic shock/resuscitation is an important contributor to late morbidity and mortality in trauma patients. Haemorrhagic shock (HS), followed by resuscitation, is considered to be an insult that frequently induces systemic inflammatory response syndrome and oxidative stress, resulting in multiple-organ dysfunction syndrome, including microvascular changes and microscopic damage termed acute lung paraynchymal injury. Montelukast is a cysteinyl leukotriene receptor antagonist that exerts an anti-inflammatory and antioxidant influence.

Methods: Eighteen adult albino rats were assigned to three groups of six. In Group I, the 'sham' group, rats underwent all the surgical procedures but neither haemorrhagic shock nor resuscitation was carried out. Group II--the 'HS' induced, untreated group--was the control and underwent HS for one hour before being resuscitated with Ringer's lactate for one hour. Group III--the 'montelukast' group--underwent HS and treatment with montelukast (7 mg/kg i.p. injection) 30 min before the induction of HS, with the same dose repeated just before the reperfusion period. At the end of the experiment, two hours after completion of resuscitation, blood samples were collected for measurement of serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The trachea was then isolated and bronchoalveolar lavage was carried out for measurement of leukotriene B(4) (LTB(4)), leukotriene C(4) (LTC(4)) and total protein. The lungs were harvested 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 (Group III) significantly reduced the total lung injury score, compared with the HS group (Group II) (P < 0.05). Montelukast also significantly decreased serum TNF-α and IL-6; lung MDA; bronchoalveolar lavage fluid (BALF) LTB(4), LTC(4) & total protein compared with the HS group (P < 0.05). Montelukast treatment significantly inhibited 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 by interfering with inflammatory and oxidative pathways, implicating the role of leukotrienes in the pathogenesis of haemorrhagic shock-induced lung inflammation.