Antithrombin Reduces Ischemia/Reperfusion Injury of Rat Liver by Increasing the Hepatic Level of Prostacyclin

Harada, Naoaki; Okajima, Kenji; Kushimoto, Shigeki

doi:10.1097/00003246-199901001-00067

Cited by 61 publications

(109 citation statements)

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“…Animals in the sham group were treated with vehicle for 7 d, and then laparotomized for 5 min without blocking liver inflow. [15][16][17] Four hours later, animals were sacrificed and blood samples were collected from the inferior venacava for serum biochemical markers determination. The liver was retrieved and washed in phosphate-buffered saline (PBS).…”

Section: Methodsmentioning

confidence: 99%

Cryptotanshinone Ameliorates Hepatic Normothermic Ischemia and Reperfusion Injury in Rats by Anti-mitochondrial Apoptosis

Sun

Yuan

et al. 2014

Biological & Pharmaceutical Bulletin

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Cryptotanshinone (CT), isolated from the dried roots of Salvia militorrhiza, has been reported to have protective effects on myocardial and cerebral ischemia/reperfusion (I/R) injury both in vitro and in vivo. However, its effects and underlying mechanism on hepatic I/R injury remain unclear. To investigate its effects on hepatic I/R injury, thirty male Sprague-Dawley rats were randomized into 3 groups: a sham group, a vehicle-treated hepatic I/R group and a CT-treated (50 mg/kg) group. The hepatic I/R and CT-treated groups were subjected to 60 min of normothermic ischemia of the left lateral lobe of the liver, followed by 4 h of reperfusion. The animals were then sacrificed to collect the serum and the left liver lobe for assay. Hepatic function was protected, as evidenced by significantly reduced alanine aminotransferase (ALT), aspartate aminotransferase (AST) and malondialdehyde (MDA) levels in the CT-treated group as compared with I/R group. The terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) demonstrated significantly decreased apoptosis in the CT-administration animals. Western blotting demonstrated upregulation of the proapoptotic protein Bcl-2, as well as decreased levels of the activated form of caspase-3 and the cleaved form of its substrate, poly(ADP-ribose) polymerase (PARP) in the CT-treated group compared with those of the I/R group. In addition, the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (MAPKs) was inhibited by CT. Our data suggest that CT attenuates hepatic I/R injury by inhibiting the intrinsic pathway of apoptosis, mediated partly through the inhibition of JNK and p38 MAPK phosporylation.

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Section: Methodsmentioning

confidence: 99%

Cryptotanshinone Ameliorates Hepatic Normothermic Ischemia and Reperfusion Injury in Rats by Anti-mitochondrial Apoptosis

Sun

Yuan

et al. 2014

Biological & Pharmaceutical Bulletin

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“…immediately after surgery. CR2-Crry was administered at a dose of 0.25 mg, based on effective protection in previous studies of intestinal and cerebral IRI (47,48), and at one-third the dose, 0.08 mg. CR2-Crry was prepared as previously described (47). Based on a previous study done in rats (49), IL-6 blockade was accomplished using goat antimouse IL-6 antibody (R&D Systems) injected i.p.…”

Section: Methodsmentioning

confidence: 99%

A complement-dependent balance between hepatic ischemia/reperfusion injury and liver regeneration in mice

He¹,

Atkinson²,

Qiao³

et al. 2009

J. Clin. Invest.

125

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Massive liver resection and small-for-size liver transplantation pose a therapeutic challenge, due to increased susceptibility of the remnant/graft to ischemia reperfusion injury (IRI) and impaired regeneration. We investigated the dual role of complement in IRI versus regeneration in mice. Complement component 3 (C3) deficiency and complement inhibition with complement receptor 2-complement receptor 1-related protein y (CR2-Crry, an inhibitor of C3 activation) provided protection from hepatic IRI, and while C3 deficiency also impaired liver regeneration following partial hepatectomy (PHx), the effect of CR2-Crry in this context was dose dependent. In a combined model of IRI and PHx, either C3 deficiency or high-dose CR2-Crry resulted in steatosis, severe hepatic injury, and high mortality, whereas low-dose CR2-Crry was protective and actually increased hepatic proliferative responses relative to control mice. Reconstitution experiments revealed an important role for the C3a degradation product acylation-stimulating protein (ASP) in the balance between inflammation/injury versus regeneration. Furthermore, liver regeneration was dependent on the putative ASP receptor, C5L2. Several potential mechanisms of hepatoprotection and recovery were identified in mice treated with low-dose CR2-Crry, including enhanced IL-6 expression and STAT3 activation, reduced hepatic ATP depletion, and attenuated oxidative stress. These data indicate that a threshold of complement activation, involving ASP and C5L2, promotes liver regeneration and suggest a balance between complement-dependent injury and regeneration.

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“…Hepatic tissue blood flow was measured by laser-Doppler flowmeter (ALF21N; Advance, Tokyo, Japan) during 3 h after reperfusion, as described previously (Harada et al, 1999b). After anesthesia with 100 mg/kg i.p.…”

Section: In Vivo Studymentioning

confidence: 99%

“…CINC is produced by both leukocytes and endothelial cells (Watanabe et al, 1989). Hepatic levels of CINC were determined as described previously (Harada et al, 1999b).…”

Section: In Vivo Studymentioning

confidence: 99%

Ranitidine Reduces Ischemia/Reperfusion-Induced Liver Injury in Rats by Inhibiting Neutrophil Activation

Okajima¹,

Harada²,

Uchiba³

2002

J Pharmacol Exp Ther

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We previously reported that ranitidine, an H 2 receptor antagonist, inhibited neutrophil activation in vitro and in vivo, contributing to reduce stress-induced gastric mucosal injury in rats. In this study, we examined whether ranitidine would reduce ischemia/reperfusion-induced liver injury, in which activated neutrophils are critically involved, in rats. We also examined the effect of famotidine, another H 2 receptor antagonist, on leukocyte activation in vitro and after ischemia/reperfusion-induced liver injury in rats to know whether inhibition of neutrophil activation by ranitidine might be dependent on its blockade of H 2 receptors. Ranitidine inhibited the activation of neutrophils in vitro as reported previously, whereas famotidine significantly enhanced it. Ranitidine inhibited the production of tumor necrosis factor-␣ (TNF-␣) in monocytes stimulated with lipopolysaccharide in vitro, whereas famotidine did not. Although hepatic ischemia/reperfusion-induced increases in hepatic tissue levels of TNF-␣, cytokine-induced neutrophil chemoattractant, and hepatic accumulation of neutrophils were inhibited by intravenously administered 30 mg/kg ranitidine, these increases were significantly enhanced by 5 mg/kg i.v. famotidine. The decreases in both hepatic tissue blood flow and bile secretion and the increases in serum levels of transaminases seen after reperfusion were significantly inhibited by ranitidine, whereas these changes were more marked in animals given famotidine than in controls. These observations strongly suggested that ranitidine could reduce ischemia/reperfusion-induced liver injury by inhibiting neutrophil activation directly, or indirectly by inhibiting the production of TNF-␣, which is a potent activator of neutrophils. Furthermore, the therapeutic efficacy of ranitidine might not be explained solely by its blockade of H 2 receptor.

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Antithrombin Reduces Ischemia/Reperfusion Injury of Rat Liver by Increasing the Hepatic Level of Prostacyclin

Cited by 61 publications

References 0 publications

Cryptotanshinone Ameliorates Hepatic Normothermic Ischemia and Reperfusion Injury in Rats by Anti-mitochondrial Apoptosis

Cryptotanshinone Ameliorates Hepatic Normothermic Ischemia and Reperfusion Injury in Rats by Anti-mitochondrial Apoptosis

A complement-dependent balance between hepatic ischemia/reperfusion injury and liver regeneration in mice

Ranitidine Reduces Ischemia/Reperfusion-Induced Liver Injury in Rats by Inhibiting Neutrophil Activation

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