Abstract
BackgroundHemorrhagic shock followed by resuscitation is conceived as an insult frequently induces a systemic inflammatory response syndrome and oxidative stress that results in multiple-organ dysfunction syndrome including acute lung injury. MK-886 is a leukotriene biosynthesis inhibitor exerts an anti inflammatory and antioxidant activity.ObjectivesThe objective of present study was to assess the possible protective effect of MK-886 against hemorrhagic shock-induced acute lung injury via interfering with inflammatory and oxidative pathways.Materials and methodsEighteen 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 1 hr then resuscitated with Ringer's lactate (1 hr) (induced untreated group, HS); group III, HS + MK-886 (0.6 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 trachea was then isolated and bronchoalveolar lavage fluid (BALF) was carried out for measurement of leukotriene B4 (LTB4), leukotriene C4 (LTC4) and total protein. 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.ResultsMK-886 treatment significantly reduced the total lung injury score compared with the HS group (P < 0.05). MK-886 also significantly decreased serum TNF-α & IL-6; lung MDA; BALF LTB4, LTC4 & total protein compared with the HS group (P < 0.05). MK-886 treatment significantly prevented the decrease in the lung GSH levels compared with the HS group (P < 0.05).ConclusionsThe results of the present study reveal that MK-886 may ameliorate lung injury in shocked rats via interfering with inflammatory and oxidative pathways implicating the role of leukotrienes in the pathogenesis of hemorrhagic shock-induced lung inflammation.
Highlights
Hemorrhagic shock (HS) is a commonly encountered complication within a blunt traumatic or surgical injury
MK-886 significantly decreased serum tumor necrosis factor-a (TNF-a) & IL-6; lung MDA; bronchoalveolar lavage fluid (BALF) leukotriene B4 (LTB4), leukotriene C4 (LTC4) & total protein compared with the HS group (P < 0.05)
The results of the present study reveal that MK-886 may ameliorate lung injury in shocked rats via interfering with inflammatory and oxidative pathways implicating the role of leukotrienes in the pathogenesis of hemorrhagic shock-induced lung inflammation
Summary
Hemorrhagic shock (HS) is a commonly encountered complication within a blunt traumatic or surgical injury. Hemorrhagic shock followed by resuscitation (HSR) is conceived as an insult frequently induces a systemic inflammatory response syndrome (SIRS) that results in multiple-organ dysfunction syndrome (MODS) [1,2] including acute lung injury (ALI), which is a major clinical problem, leading to significant mortality and morbidity [1,3]. The activated neutrophils appear to infiltrate the injured lung in parallel with increased expression of adhesion molecules on endothelial cells and elevated local chemokines/cytokines levels following HS [7]. Hemorrhagic shock followed by resuscitation is conceived as an insult frequently induces a systemic inflammatory response syndrome and oxidative stress that results in multiple-organ dysfunction syndrome including acute lung injury. MK-886 is a leukotriene biosynthesis inhibitor exerts an anti inflammatory and antioxidant activity
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