Beneficial Effects of Inducible Nitric Oxide Synthase Inhibitor on Reperfusion Injury in the Pig Liver

Abstract

These results indicate that hepatic I/R injury is triggered by centrilobular iNOS expression; and attenuated by inhibition of iNOS.

In vivo regulation of inducible NO synthase in immune-mediated liver injury in mice

“…20 In the case of ischemia/reperfusion injury, both hepatoprotective as well as hepatotoxic effects of NO have been described. 17,26,27 Because TNF, IFN-␥, and iNOS are crucial mediators of liver injury after administration of con A 4,6,20 and both cytokines have been shown to induce iNOS, 12 we investigated the relationship between TNF, its receptors, IFN-␥, and iNOS induction in the liver following injection of con A. Here we show that a combination of both cytokines is required to induce iNOS in vivo.…”

“…Under normal conditions, only the constitutive endothelial NOS is present in the liver and low levels of NO regulate the hepatic perfusion. 14 Under certain conditions (e.g., endotoxemia, 15 hemorrhagic shock, 16 ischemia/reperfusion injury, 17 viral hepatitis, 18 and liver regeneration 19 ), iNOS is strongly up-regulated and large amounts of NO are generated in the liver. A rapid up-regulation of iNOS in vitro is found in hepatic resident macrophages (Kupffer cells) and in hepatocytes after a stimulus of lipopolysaccharide or proinflammatory cytokines such as TNF, IL-1␤, and IFN-␥ 10,12 as well as in vivo after administration of con A.…”

Nitric oxide in gingival crevicular fluid and nitric oxide synthase expression in the gingiva of patients with sickle cell disease

“…Immunohistochemical slides were examined for positive staining using light microscopy. Inflammation in each case was rated according to a modified scoring system [40][41] shown in Table 1, as follows: no inflammation (0), minimal inflammation (1), mild inflammation (2), moderate inflammation (3), and diffuse inflammation (4). In all, 5 high-power fields (40× magnification) per patient and control sample were examined, and the percentage of inflammatory cells expressing iNOS was scored as 0 (0%-1%), 1 (2%-20%), 2 (21%-50%), and 3 (≥51%).…”

“…Interactions between abnormal rigid erythrocytes and the vascular wall result in endothelial activation, which may lead to endothelial damage and tissue ischaemia in SCD. Chronic inflammation during both the steady state and vasoocclusive crisis occurs via the action of cytokines and other inflammatory factors [1][2][3][4]. The clinical manifestations of the disease, such as painful crises, anemia, bone necrosis, and leg ulceration, arise due to chronic hemolysis, vaso-occlusion, ischemia, and tissue damage.…”

“…Increased iNOS expression and a consequent increase in tissue nitrite and nitrate production have been observed in the kidneys and liver of SCD patients [8], mice [2,3,8,9], and pigs [4]. Additionally, it was shown that iNOS inhibition significantly limits tissue ischemia-reperfusion injury in the liver and kidneys [10,11]; however, inhibition of iNOS attenuated ischemia-reperfusion injury in the rat heart [12] and did not affect ischemia-reperfusion injury in the rat lung [13].…”