Role of inducible nitric oxide synthase in pig liver transplantation

Kimura, Hitoshi; Kimura, Tadashi; Isobe, Masato; Nagayama, Masatoshi; Meguro, Makoto; Kukita, Kazuma; Nui, Akihiro; Hirata, Koichi

doi:10.1016/s0022-4804(03)00036-2

Cited by 44 publications

(37 citation statements)

References 42 publications

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“…Peroxynitrite itself has dual effects, with possible hepatoprotection through decreased leukocyte adhesion and infiltration (55). Results from a porcine liver transplant model suggest that IRI may be triggered by iNOS in Kupffer cell and PMNs (56). Similarly, steatotic rat livers subjected to IR show upregulation of iNOS and endothelin (ET-1), suggesting an important role in regulation of sinusoidal perfusion (57).…”

Section: Nitric Oxide (No)mentioning

confidence: 99%

Molecular Mediators of Liver Ischemia and Reperfusion Injury: A Brief Review

Vardanian¹,

Busuttil²,

Kupiec‐Weglinski³

2008

Mol Med

141

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Ischemia and reperfusion injury is a dynamic process that involves multiple organ systems in various clinical states including transplantation, trauma, and surgery. Research into this field has identified key molecular and signaling players that mediate, modulate, or augment cellular, tissue, and organ injury during this disease process. Further elucidation of the molecular mechanisms should provide the rationale to identify much-needed novel therapeutic options to prevent or ameliorate organ damage due to ischemia and reperfusion in clinics.

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Section: Nitric Oxide (No)mentioning

confidence: 99%

Molecular Mediators of Liver Ischemia and Reperfusion Injury: A Brief Review

Vardanian¹,

Busuttil²,

Kupiec‐Weglinski³

2008

Mol Med

141

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“…This process leads to the production of peroxynitrite, which is a potent oxidant and induces cell death 10 . Peroxynitrite has dual effects; it can be harmful 8 , or it can promote hepatoprotection via a decrease in leukocyte adhesion and infiltration 13 . Our results suggest that the delivery of NO is protective, depending on the phase during which it enters the cascade of events in liver IRI.…”

Section: Discussionmentioning

confidence: 99%

“…In animal models of IRI, inhibitors of NOS promote tissue injury 11 . However, high tissue levels of NO may also have harmful effects [12][13][14][15][16] . 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 .…”

Section: Introductionmentioning

confidence: 99%

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L-arginine in the ischemic phase protects against liver ischemia-reperfusion injury

et al. 2012

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PURPOSE:To investigate the effects of intravenous L-arginine (LG) infusion on liver morphology, function and proinflammatory response of cytokines during the early phase of ischemia-reperfusion injury (IRI). METHODS: Thirty rabbits were subjected to 60 minutes of hepatic ischemia and 120 minutes of reperfusion. An intravenous injection of saline or L-arginine was administered five minutes before the ischemia and five minutes before initiating the reperfusion and at the 55 th and 115 th minutes after the ischemia. Samples were collected for histological analysis of the liver and measurements of the serum AST, ALT and LDH and the cytokines IL-6 and TNF-alpha. RESULTS: It was observed a significant reduction of sinusoidal congestion, cytoplasmic vacuolization, infiltration of polymorphonuclear leukocyte, nuclear pyknosis, necrosis and steatosis in liver tissue, as well as AST, ALT and LDH after injection of LG in the ischemia (p <0.001). Lower levels of IL-6 and TNF-alpha were associated with LG infusion during ischemia. Higher levels these proteins were observed in animals receiving LG during reperfusion. CONCLUSION: L-arginine protects the liver against ischemia/reperfusion injury, mainly when is administered during the ischemic phase. Key words: Nitric Oxide. Arginine. Warm Ischemia. Cytokines. Antioxidants. Interleukin-6. Liver. Rabitts. RESUMO OBJETIVO:Investigar os efeitos da infusão endovenosa da L-arginina (LG) na morfologia, função e resposta de citocinas pró-inflamatórias do fígado durante a fase precoce da lesão de isquemia e reperfusão (IRI). MÉTODOS: Trinta coelhos foram submetidos a 60 minutos de isquemia hepática e 120 minutos de reperfusão. Foi administrada injecção intravenosa de solução salina ou L-arginina aos cinco minutos antes de iniciar a isquemia e cinco minutos antes de iniciar a reperfusão e aos 55 e 115 minutos após o início da isquemia. Realizou-se análise histológica do fígado e dosagens séricas de AST, ALT, LDH, citocinas IL-6 e TNF-alfa. RESULTADOS: Ocorreu redução significante da congestão sinusoidal, vacuolização citoplasmática, infiltração de leucócitos polimorfonucleares, picnose nuclear, necrose e esteatose no tecido hepático, assim como nos níveis de AST, ALT e LDH após a injeção da LG na isquemia (p<0,001). Níveis mais baixos de IL-6 e TNF-alfa foram associados com a infusão LG durante a isquemia. Níveis mais elevados dessas proteínas foram observados nos animais que receberam LG durante a reperfusão. CONCLUSÃO: A L-arginina protegeu o fígado contra a lesão de isquemia e reperfusão principalmente quando administrada durante a fase de isquemia. Descritores: Óxido Nítrico. Arginina. Isquemia Quente. Citocinas. Antioxidantes. Interleucina-6. Fígado. Coelhos. L-arginine in the ischemic phase protects against liver ischemia-reperfusion injuryActa

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“…The longer the ischemia time, the worse the cognitive function was. When hepatic I/R occurs, plenty of hazardous substances produced by the liver including free radicals and inflammatory cytokines flow to the brain via the blood (Kimura et al, 2003). On the one hand, vascular endothelial cells in brain tissue are directly affected and brain cells suffer immediate damage (including mechanisms involving energy metabolism and blood-brain barrier).…”

mentioning

confidence: 99%

Influence of hepatic ischemia-reperfusion on postoperative spatial cognitive function in mice

Wang¹,

Wu²,

Wang³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. The aim of this study was to investigate the effects of partial hepatic ischemia/reperfusion (I/R) on postoperative cognitive function in mice. One hundred Kunming mice were randomized into control group (N = 20), sham group (N = 20) and I/R group (N = 60), which was equally divided into 3 subgroups according to the ischemia time (20, 30 and 40 min). Half of the mice in each group underwent a passive avoidance test on the 4th day, and the other underwent the test on the 18th day, which lasted for 6 days before euthanasia for analysis of brain pathology and immunohistochemistry for ChAT. The passive avoidance test showed that there was no significance in the incubation period and number of errors between the control and sham group, but there was a longer incubation period and more errors in the I/R group than control group; at G2, there was no significance between all groups. Hematoxylin-eosin staining of the hippocampus showed that at G1, there was no obvious change in hippocampal neurons in structure and arrangement except for IR/40 min; at G2, there was no significance between all groups. Immunohistochemistry of hippocampus for ChAT showed the following: at G1, there was no significance in average optical density of CA3 area between control and sham group, but optical density was significantly lower in I/R groups with I/R 40 min showing the lowest; at G2, there was no significance between all groups. Pentobarbital has no effect on cognitive function, but hepatic partial ischemia and reperfusion injury does and could become worse over time.

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Role of inducible nitric oxide synthase in pig liver transplantation

Cited by 44 publications

References 42 publications

Molecular Mediators of Liver Ischemia and Reperfusion Injury: A Brief Review

Molecular Mediators of Liver Ischemia and Reperfusion Injury: A Brief Review

L-arginine in the ischemic phase protects against liver ischemia-reperfusion injury

Influence of hepatic ischemia-reperfusion on postoperative spatial cognitive function in mice

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