2007
DOI: 10.1152/ajpgi.00227.2006
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Liver I/R injury is improved by the arginase inhibitor, Nω-hydroxy-nor-l-arginine (nor-NOHA)

Abstract: Liver ischemia-reperfusion (I/R) injury is associated with profound arginine depletion due to arginase release from injured hepatocytes. The purpose of this study was to determine whether arginase inhibition with N -hydroxy-nor-L-arginine (nor-NOHA) would increase circulating arginine levels and decrease hepatic damage during liver I/R injury. The effects of nor-NOHA were initially tested in normal animals to determine in vivo toxicity. In the second series of experiments, orthotopic syngeneic liver transplant… Show more

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Cited by 51 publications
(42 citation statements)
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“…Measuring serum levels of nitrite and other more direct markers of nitric oxide production would be useful in determining whether the increased arginine following nor-NOHA protects via an NO-dependent mechanism. It is noteworthy that nor-NOHA treatment also restored the depleted levels of circulating arginine levels in a rodent model of liver transplantation, and improved liver graft injury [19]. Furthermore, some therapeutic interventions that may be beneficial in the cold I/R setting have not been proven to apply in warm hepatic I/R models.…”
Section: Discussionmentioning
confidence: 99%
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“…Measuring serum levels of nitrite and other more direct markers of nitric oxide production would be useful in determining whether the increased arginine following nor-NOHA protects via an NO-dependent mechanism. It is noteworthy that nor-NOHA treatment also restored the depleted levels of circulating arginine levels in a rodent model of liver transplantation, and improved liver graft injury [19]. Furthermore, some therapeutic interventions that may be beneficial in the cold I/R setting have not been proven to apply in warm hepatic I/R models.…”
Section: Discussionmentioning
confidence: 99%
“…Our selection of dosing regimen was based on previous testing of nor-NOHA in normal animals where doses up to 200 mg/kg IV × 2 resulted in no changes AST, ALT, or creatinine. Doses up to 400 mg/kg IV × 2 resulted in minimal increases in AST and ALT with no increase in creatinine [19]. Therefore the dose used in the current study (100 mg/kg I.V.…”
Section: Experimental Designmentioning
confidence: 93%
“…Hepatoprotection via the LG-NOS pathway has been previously established in animal models of IRI 18,19 . Given that the LG-NOS pathway has been reported to play critical roles during inflammation, our data support the hypothesis that the administration of LG during the ischemic phase is beneficial by attenuating liver injury in a model of warm hepatic IRI.…”
Section: Intravenousmentioning
confidence: 99%
“…Collectively, these observations suggest a balance between the local NO concentration and the time of NO exposure in determining the outcome of liver IRI 8 . Irrespective of the precise mechanisms involved, increased inflammation and cytotoxicity are key components in hepatocellular dysfunction during the pathogenesis of liver IRI [16][17][18][19][20] .…”
Section: Introductionmentioning
confidence: 99%
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