Apoptosis and necrosis after warm ischemia-reperfusion injury of the pig liver and their inhibition by ONO-1714

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

doi:10.1097/01.tp.0000053400.42842.5c

Cited by 34 publications

(30 citation statements)

References 23 publications

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“…Isolated studies, however, did not show apoptosis 2 or found necrosis as the dominant finding 20 . In those papers, however, ischemic time seemed to be excessive.…”

Section: Discussionmentioning

confidence: 99%

“…Tissue dysfunction is secondary to all these events. Duration of ischemia influences the degree of injury, although many of the injuries appear in the reperfusion phase 5,7,18,20,29 .…”

Section: Discussionmentioning

confidence: 99%

“…The I/R injury results in microcirculatory failure, followed by cell death, thus protecting the hepatocytes of this event is important for liver surgery. Several mechanisms have been proposed to explain the I/R injury, but its pathophysiology is still not entirely clear 7,20,27,29,30 . Apoptosis is a special type of cell death, where the cell is stimulated to trigger mechanisms that will culminate with his own death.…”

Section: Introductionmentioning

confidence: 99%

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Lesão de isquemia e reperfusão após clampagem contínua ou intermitente do pedículo hepático em coelhos

Seabra

Savassi-Rocha

Vasconcelos

et al. 2012

ABCD, arq. bras. cir. dig.

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-Background -The control of bleeding in hepatectomy is a challenge for surgeons. The hepatic pedicle clamping is a surgical maneuver that can provide reduction in bleeding, but it provokes a hepatocellular suffering. This, along with reperfusion after the clamping finishes, leads to an injury known as ischemia/reperfusion injury. Aim -To examine the effects of the ischemia/reperfusion injury on the liver after continuous and intermittent hepatic pedicle clamping in an animal model, using the quantification of apoptosis for evaluation. Method -Twenty New Zealand rabbits were assigned to groups 1 (control), 2 (60 minutes of continuous ischemia) and 3 (60 minutes of intermittent ischemia alternating 12 minutes of ischemia and three minutes of reperfusion). Liver biopsies were collected before ischemia, at its end and after six hours of reperfusion, when the animals were killed. The liver fragments were subjected to histological analysis (paraffinization and hematoxilin-eosin staining) and histochemical (Tunel reaction). Microscope fields of view were scanned for characterization and quantification of apoptosis. Results -Ischemia led to an increased apoptotic index in both experimental groups in comparison to controls, but similarly between them. After the reperfusion, the indexes returned to baseline values. Conclusion -Clamping of the hepatic pedicle, either continuous or intermittent, induces apoptosis in liver cells in a similar way. ABCDDV/852RESUMO -Racional -O controle do sangramento na hepatectomia é um desafio para os cirurgiões. A clampagem do pedículo hepático é manobra cirúrgica que pode promover redução do sangramento, mas provoca isquemia hepatocelular. Isso, junto com a reperfusão depois que a clampagem termina, leva à lesão de isquemia e reperfusão. Objetivo -Examinar os efeitos da lesão de isquemia e reperfusão no fígado após clampagem contínua e intermitente do pedículo hepático, usando a quantificação de apoptose como ferramenta. Método -Vinte coelhos New Zealand foram divididos em grupos 1 (controle), 2 (60 minutos de isquemia contínua) e 3 (60 minutos de isquemia intermitente alternando 12 minutos de isquemia e três minutos de reperfusão). Biópsias hepáticas foram colhidas antes e ao fim da isquemia e após seis horas de reperfusão, quando os animais eram sacrificados. Os fragmentos obtidos foram submetidos à análise histológica e histoquímica (reação de Tunel). Campos microscópicos foram analisados para caracterização e quantificação de apoptose. Resultados -A isquemia levou à elevação do índice apoptótico em ambos os grupos experimentais em relação aos controles, mas similar entre eles. Depois da reperfusão os índices voltaram aos valores iniciais. Conclusão -A clampagem do pedículo hepático, tanto contínua quanto intermitente, induz a apoptose em células hepáticas de modo igual.

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“…Isolated studies, however, did not show apoptosis 2 or found necrosis as the dominant finding 20 . In those papers, however, ischemic time seemed to be excessive.…”

Section: Discussionmentioning

confidence: 99%

“…Tissue dysfunction is secondary to all these events. Duration of ischemia influences the degree of injury, although many of the injuries appear in the reperfusion phase 5,7,18,20,29 .…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Lesão de isquemia e reperfusão após clampagem contínua ou intermitente do pedículo hepático em coelhos

Seabra

Savassi-Rocha

Vasconcelos

et al. 2012

ABCD, arq. bras. cir. dig.

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“…In a pig model of liver ischemia-reperfusion, sinusoidal cell and hepatocyte apoptosis has been shown to increase over time and to almost return to background level after 24 h of reperfusion. 5 In addition, more than 35% of hepatocytes have been found to undergo necrosis. 5 As our samples were collected 15 days post reperfusion, it cannot be excluded that a massive apoptosis occurred shortly after transplantation and therefore may have been at the origin of the calcification process.…”

Section: Characterization Of Liver Injurymentioning

confidence: 99%

“…In addition to necrosis, liver cell apoptosis may also predispose to calcification as previously described. 4 Both necrosis and apoptosis have been shown to be massively triggered during experimental ischemia-reperfusion performed in pig liver, 5 thus suggesting a potential link between ischemiareperfusion and the observed calcifications. In spite of small patient number, calcification was found in 60% of liver disfunctions following human liver transplantation.…”

mentioning

confidence: 99%

Cellular and molecular mechanisms of abnormal calcification following ischemia–reperfusion injury in human liver transplantation

et al. 2007

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Recent studies suggest a possible link between calcification and ischemia-reperfusion injury following liver transplantation. Histological staining, immunolabeling, and biochemical and electron microscopy analyses were applied to assess the possible mechanism(s) of calcification in liver tissue. Although light microscopy studies did not reveal the presence of large necrotic or apoptotic areas, electron microscopy showed the presence of membrane-bound vacuolar structures in hepatocytes, indicative of cell damage. Myofibroblasts were abundant in regions surrounding and within calcification. In these precalcified and calcified areas, myofibroblasts expressed bone-specific matrix proteins, such as osteopontin, type 1 collagen and bone sialoprotein. In addition, transforming growth factor beta (TGFb)-1 and BMP2, two growth factors implicated in osteoblast differentiation, and Runx2 and Msx2, two transcription factors targets of TGFb-1 and BMP2, were also expressed in these myofibroblasts. These data suggest that liver calcification following transplantation may be a consequence of precipitation of hydroxylapatite emanating from necrotic or apoptotic hepatocytes associated with proliferation of myofibroblasts expressing bone-specific matrix proteins.

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Highest intraoperative lactate level could predict postoperative infectious complications after hepatectomy, reflecting the Pringle maneuver especially in chronic liver disease

Meguro

Mizuguchi

Kawamoto

et al. 2014

J Hepatobiliary Pancreat Sci

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Apoptosis and necrosis after warm ischemia-reperfusion injury of the pig liver and their inhibition by ONO-1714

Abstract: A major mode of cell death during hepatic warm I/R injury was necrosis, and apoptosis was not dominant. These necrotic changes were caused by the excess production of peroxynitrite, and ONO-1714 greatly attenuated I/R injuries as the result of inhibition of the peroxynitrite production.

Cited by 34 publications

References 23 publications

Lesão de isquemia e reperfusão após clampagem contínua ou intermitente do pedículo hepático em coelhos

Lesão de isquemia e reperfusão após clampagem contínua ou intermitente do pedículo hepático em coelhos

Cellular and molecular mechanisms of abnormal calcification following ischemia–reperfusion injury in human liver transplantation

Highest intraoperative lactate level could predict postoperative infectious complications after hepatectomy, reflecting the Pringle maneuver especially in chronic liver disease

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