Role of nitric oxide in hepatic ischemia-reperfusion injury

Arunotai Siriussawakul, Ahmed Zaky, John D Lang, Arunotai Siriussawakul, Ahmed Zaky, John D Lang

Abstract

Hepatic ischemia-reperfusion injury (IRI) occurs upon restoration of hepatic blood flow after a period of ischemia. Decreased endogenous nitric oxide (NO) production resulting in capillary luminal narrowing is central in the pathogenesis of IRI. Exogenous NO has emerged as a potential therapy for IRI based on its role in decreasing oxidative stress, cytokine release, leukocyte endothelial-adhesion and hepatic apoptosis. This review will highlight the influence of endogenous NO on hepatic IRI, role of inhaled NO in ameliorating IRI, modes of delivery, donor drugs and potential side effects of exogenous NO.

Figures

Figure 1
Figure 1
Multifaceted hepatic ischemia-reperfusion injury. Kupffer and endothelial cells produce cytokines and chemokines, recruiting neutrophils that further accentuate injury. EC: Endothelial cell; KC: Kupffer cell; ATP: Adenosine triphosphate; TNF: Tumor necrosis factor; IL: Interleukin; ICAM: Intercellular adhesion molecule; VCAM: Vascular adhesion molecule; PAF: Platelet activation factor; LTB4: Leukotriene B4; GMS-CSF: Granulocyte macrophage colony stimulating factor; INF: Interferon; ROS: Reactive oxygen species (Courtesy of Dr. Joan Rosello-Catafau, Barcelona, Spain).
Figure 2
Figure 2
Increased liver injury as assessed by serum alanine aminotransferase in endothelium-derived nitric oxide synthase knockout mice compared with their wild type controls. aP < 0.05 vs sham-operated controls. cP < 0.05 vs time-matched wild type control. ALT: Alanine aminotransferase; eNOS: Endothelium-derived nitric oxide synthase (Courtesy of Dr. Ianes N. Hines, Chapel Hill, NC).
Figure 3
Figure 3
Decreased apoptosis indicated by TUNEL staining in patients treated with inducible nitric oxide compared to controls (Courtesy of John D. Lang, MD, Seattle, WA). aP < 0.05. iNO: Inducible nitric oxide.

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