Meconium-induced release of nitric oxide in rabbit alveolar cells

Abstract

Previous studies have shown meconium-induced lung injury occurs throughout release of inflammatory cytokines. The exact mechanism of cytokine-induced apoptosis is not known. In this study we hypothesized that meconium-induced apoptosis in the lungs is mediated through the production of inducible nitric oxide (NO). We studied two groups of newborn rabbit pups: one group was instilled with meconium and other with normal saline. We measured precursors of NO in lung lavage from both groups of rabbits and NO levels were calculated accordingly. The levels of NO and NO-derivatives increased significantly in both groups. However NO expression in meconium group 2 h after meconium instillation was significantly higher than in saline-instilled group suggesting NO production plays a role in meconium-induced inflammation.

Approach to the Connection between Meconium Consistency and Adverse Neonatal Outcomes: A Retrospective Clinical Review and Prospective In Vitro Study

“…Therefore, the association between elevated nitrite levels and reduced lung cell viability following meconium stimulation suggests that NO may play an important role in the pathogenesis of meconium-associated lung injury. The involvement of NO in meconium-associated lung injury has previously been studied [ 41 , 95 , 96 , 97 , 98 , 99 ]. Although the idea that elevated levels of NO might contribute to tissue damage is not new, our results showed HEL299 cells generated higher nitrite levels than A549 cells ( Figure 3 ); therefore, previous experiments using A549 cells may not accurately represent the extent of lung injuries caused by meconium exposure.…”

“…Various studies of animals and cell lines examining the effects of meconium exposure have indicated the involvement of inflammatory mediators, such as NO and COX [ 41 , 95 , 96 , 97 , 98 ]. NO is required for vasodilation in PPHN and may cause other pathological changes in the body associated with the activation of inflammatory cells and cytokines, especially during lung injury [ 100 , 101 ].…”

Stabilization and Resuscitation of Newborns

“…Therefore, the association between elevated nitrite levels and reduced lung cell viability following meconium stimulation suggests that NO may play an important role in the pathogenesis of meconium-associated lung injury. The involvement of NO in meconium-associated lung injury has previously been studied [41,[95][96][97][98][99]. Although the idea that elevated levels of NO might contribute to tissue damage is not new, our results showed HEL299 cells generated higher nitrite levels than A549 cells (Figure 3); therefore, previous experiments using A549 cells may not accurately represent the extent of lung injuries caused by meconium exposure.…”

“…Various studies of animals and cell lines examining the effects of meconium exposure have indicated the involvement of inflammatory mediators, such as NO and COX [41,[95][96][97][98]. NO is required for vasodilation in PPHN and may cause other pathological changes in the body associated with the activation of inflammatory cells and cytokines, especially during lung injury [100,101].…”

Experimental Models of Acute Lung Injury in the Newborns

“…Meconium is a potent activator of a complement which is likely associated with systemic inflammatory response and oxidative burst ). Furthermore, exposure to meconium enhances production of NO and its derivatives (Fontanilla et al 2008), and triggers a significant oxidative stress leading to peroxidation of lipids (demonstrated by TBARS) and proteins (expressed by 3-nitrotyrosine, dityrosine, lysinelipid peroxidation products etc.) in the lung (Mokra et al 2007) and increases the oxidation markers also in the plasma (Kopincova et al 2014.…”