N-Acetylcysteine Ameliorates Reperfusion Injury After Warm Hepatic Ischemia

Fukuzawa, Kengo; Emre, Sukru; Şenyüz, Osman Faruk; Acarlı, Koray; Schwartz, Myron; Miller, Charles M.

doi:10.1097/00007890-199501150-00002

Cited by 85 publications

(67 citation statements)

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“…Pretreatment with NAC helped maintain hepatic glutathione levels during warm ischemia, whereas when administered after ischemia and before reperfusion, NAC was effective in replenishing depleted glutathione stores in pigs. 6 In these animals, NAC improved bile output and increased survival rates. This effect on glutathione stores may explain the clinical results reported by Harrison et al in the treatment of acetaminophen-induced liver failure in humans.…”

Section: Discussionmentioning

confidence: 92%

Does N-acetylcysteine improve hemodynamics and graft function in liver transplantation?

et al. 1998

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The release of toxic oxidative free radicals induced by ischemia and reperfusion may jeopardize liver graft function. N-acetylcysteine (NAC) has shown protective effects on hypothermic and warm ischemia reperfusion liver injury in animals. NAC improves hemodynamics and survival rates in patients with fulminant hepatic failure. The aim of this study was to investigate whether intraoperative treatment with NAC would improve hemodynamics and postoperative graft function in liver transplantation. Sixty patients with chronic endstage liver disease were included in a prospective randomized placebo-controlled study. NAC or the same volume of 5% glucose was started during the anhepatic phase. Hemodynamic data and calculated tissue oxygenation parameters were compared throughout the procedure. Postoperative graft function was assessed by measurements of aminotransferases, prothrombin time, and monoethylglycinexylidide test over the 3 first postoperative days. Patient demographics were similar before the infusion of NAC or glucose. Hemodynamic parameters, oxygen consumption, oxygen delivery, oxygen extraction ratio, and lactates were not different throughout the procedure. One hour after the revascularization of the hepatic artery, the oxygen extraction ratio by the liver was similar (17% ؎ 7.6% v 17% ؎ 6.2%) in both groups. Postoperative graft function was comparable within the 3 first postoperative days. This study failed to show any beneficial effect of the intraoperative administration of NAC on hemodynamics and graft function in liver transplantation in patients with chronic liver disease.

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Section: Discussionmentioning

confidence: 92%

Does N-acetylcysteine improve hemodynamics and graft function in liver transplantation?

et al. 1998

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“…14 A previous study on ischemia-reperfusion injury in NZW rabbits found that an ischemia time of 20 min did not produce significant liver injury whereas an ischemia time of 30 min caused severe liver injury. 15 Although the primary objective to administer N-acetylcysteine in the current study was the prevention of reperfusion injury after warm hepatic ischemia, 16 N-acetylcysteine may have positive effects on the diameter of fenestrae by increasing the bioavailability of NO. 17 Large species variations of the diameter of sinusoidal fenestrae between cow, pig, guinea pig, sheep and dog were demonstrated by Higashi et al 18 The average diameter obtained by scanning electron microscopy was 45 nm in cows, 52 nm in sheep, 66 nm in guineapig, 82 nm in pig and 131 nm in dog but the confidence intervals for each species were large.…”

Section: Discussionmentioning

confidence: 98%

Species differences in transgene DNA uptake in hepatocytes after adenoviral transfer correlate with the size of endothelial fenestrae

et al. 2007

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“…The mechanism of this phenomenon has been explained as follows. ATP depletion [12,191 and the increase in intracellular calcium activate various enzymes and affect the cellular structure and the permeability of cell membrane [13, 15,211. In addition, metabolites in the arachidonic acid cascade are also associated with the deterioration in sinusoidal endothelial cells and coagulopathy of sinusoid.…”

Section: Discussionmentioning

confidence: 99%

Kupffer cells play an important role in the cytokine production and activation of nuclear factors of liver grafts from non-heart-beating donors

et al. 2002

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In the non-heart-beating donor (NHBD) deterioration of microcirculation of the liver graft is strongly associated with secretion of cytokines and eicosanoids. In this study we investigated the excretion of cytokines, eicosanoids, and DNA binding activity of transcription factors in the grafts from NHBD and evaluated the effects of the elimination of Kupffer cells on them. The purpose of this study was to clarify the impact of Kupffer cells on transcription factor activity and the that of cytokine and eicosanoid production on reperfusion injury of liver grafts from NHBD. Wistar rats were allocated to four groups: (a) control group: livers were extracted under heart-beating conditions and perfused without cold storage, (b) heart beating (HB) group: livers extracted under heart-beating conditions were perfused after 6 h of cold storage, (c) non-heart-beating (NHB) group: livers extracted after cardiac arrest were perfused after cold storage, (d) Kupffer cell eliminated (KE) group: liposome-encapsulated dichloromethylene diphosphonate was intravenously administered to eliminate Kupffer cells before extraction, and the liver was perfused after cold storage. Cytokines and eicosanoids in perfusate were measured. DNA binding activity of nuclear factor KB, activating protein 1, and nuclear factor-interleukin 6 of tissue were investigated. Concentrations of interleukin lfi and thromboxane B2 in the perfusate were significantly higher in NHB group, but they were completely suppressed in the KE group. A rise in binding activity of nuclear factor KB and activating protein 1 was not observed during cold storage in any groups, but these activities did increase remarkably after reperfusion. Significant buildup of those activities were recognized in the NHB group, and this phenomenon was inhibited in the KE group. The histological structures of the sinusoid in the KE group were well maintained, as with those of the control group. These results indicate that cytokines, eicosanoids, and the DNA binding activity of the transcripton factor are strongly associated with reperfusion injury, and Kupffer cells play an important role in this mechanism in grafts from NHBDs.

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N-Acetylcysteine Ameliorates Reperfusion Injury After Warm Hepatic Ischemia

Cited by 85 publications

References 0 publications

Does N-acetylcysteine improve hemodynamics and graft function in liver transplantation?

Does N-acetylcysteine improve hemodynamics and graft function in liver transplantation?

Species differences in transgene DNA uptake in hepatocytes after adenoviral transfer correlate with the size of endothelial fenestrae

Kupffer cells play an important role in the cytokine production and activation of nuclear factors of liver grafts from non-heart-beating donors

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