Regulation of postischemic liver injury following different durations of ischemia

Ian N. Hines; Jason M. Hoffman; Heleen Scheerens; Brian J. Day; Hirohisa Harada; Kevin P. Pavlick; Sulaiman Bharwani; Robert Wolf; Bifeng Gao; Sonia Flores; Joe M. McCord; Matthew B. Grisham

doi:10.1152/ajpgi.00400.2002

Regulation of postischemic liver injury following different durations of ischemia

Ian N. Hines, Jason M. Hoffman, Heleen Scheerens, Brian J. Day, Hirohisa Harada, Kevin P. Pavlick, Sulaiman Bharwani, Robert Wolf, Bifeng Gao, Sonia Flores, Joe M. McCord, Matthew B. Grisham

Research output: Contribution to journal › Article › peer-review

52 Citations (Scopus)

Abstract

The objective of this study was to define the relationship among Kupffer cells, O₂^- production, and TNF-α expression in the pathophysiology of postischemic liver injury following short and long periods of ischemia. Using different forms of superoxide dismutase with varying circulating half-lives, a monoclonal antibody directed against mouse TNF-α, and NADPH oxidase-deficient mice, we found that 45 or 90 min of partial (70%) liver ischemia and 6 h of reperfusion (I/R) produced time-dependent increases in liver injury and TNF-α expression in the absence of neutrophil infiltration. Furthermore, we observed that hepatocellular injury induced by short periods of ischemia were not dependent on formation of TNF-α but were dependent on Kupffer cells and NADPH oxidase-independent production of O₂^-. However, liver injury induced by extended periods of ischemia appeared to require the presence of Kupffer cells, NADPH oxidase-derived O₂^-, and TNF-α expression. We conclude that the sources for O₂^- formation and the relative importance of TNF-α in the pathophysiology of I/R-induced hepatocellular injury differ depending on the duration of ischemia.

Original language	English
Pages (from-to)	G536-G545
Journal	American Journal of Physiology - Gastrointestinal and Liver Physiology
Volume	284
Issue number	3 47-3
DOIs	https://doi.org/10.1152/ajpgi.00400.2002
Publication status	Published - Mar 1 2003
Externally published	Yes

Keywords

Leukocytes
NADPH oxidase
Proinflammatory cytokines
Reactive oxygen species
Transplantation

ASJC Scopus subject areas

Physiology
Hepatology
Gastroenterology
Physiology (medical)

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10.1152/ajpgi.00400.2002

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Hines, I. N., Hoffman, J. M., Scheerens, H., Day, B. J., Harada, H., Pavlick, K. P., Bharwani, S., Wolf, R., Gao, B., Flores, S., McCord, J. M., & Grisham, M. B. (2003). Regulation of postischemic liver injury following different durations of ischemia. American Journal of Physiology - Gastrointestinal and Liver Physiology, 284(3 47-3), G536-G545. https://doi.org/10.1152/ajpgi.00400.2002

Hines, IN, Hoffman, JM, Scheerens, H, Day, BJ, Harada, H, Pavlick, KP, Bharwani, S, Wolf, R, Gao, B, Flores, S, McCord, JM & Grisham, MB 2003, 'Regulation of postischemic liver injury following different durations of ischemia', American Journal of Physiology - Gastrointestinal and Liver Physiology, vol. 284, no. 3 47-3, pp. G536-G545. https://doi.org/10.1152/ajpgi.00400.2002

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abstract = "The objective of this study was to define the relationship among Kupffer cells, O2- production, and TNF-α expression in the pathophysiology of postischemic liver injury following short and long periods of ischemia. Using different forms of superoxide dismutase with varying circulating half-lives, a monoclonal antibody directed against mouse TNF-α, and NADPH oxidase-deficient mice, we found that 45 or 90 min of partial (70%) liver ischemia and 6 h of reperfusion (I/R) produced time-dependent increases in liver injury and TNF-α expression in the absence of neutrophil infiltration. Furthermore, we observed that hepatocellular injury induced by short periods of ischemia were not dependent on formation of TNF-α but were dependent on Kupffer cells and NADPH oxidase-independent production of O2-. However, liver injury induced by extended periods of ischemia appeared to require the presence of Kupffer cells, NADPH oxidase-derived O2-, and TNF-α expression. We conclude that the sources for O2- formation and the relative importance of TNF-α in the pathophysiology of I/R-induced hepatocellular injury differ depending on the duration of ischemia.",

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AU - Hoffman, Jason M.

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AU - Pavlick, Kevin P.

AU - Bharwani, Sulaiman

AU - Wolf, Robert

AU - Gao, Bifeng

AU - Flores, Sonia

AU - McCord, Joe M.

AU - Grisham, Matthew B.

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N2 - The objective of this study was to define the relationship among Kupffer cells, O2- production, and TNF-α expression in the pathophysiology of postischemic liver injury following short and long periods of ischemia. Using different forms of superoxide dismutase with varying circulating half-lives, a monoclonal antibody directed against mouse TNF-α, and NADPH oxidase-deficient mice, we found that 45 or 90 min of partial (70%) liver ischemia and 6 h of reperfusion (I/R) produced time-dependent increases in liver injury and TNF-α expression in the absence of neutrophil infiltration. Furthermore, we observed that hepatocellular injury induced by short periods of ischemia were not dependent on formation of TNF-α but were dependent on Kupffer cells and NADPH oxidase-independent production of O2-. However, liver injury induced by extended periods of ischemia appeared to require the presence of Kupffer cells, NADPH oxidase-derived O2-, and TNF-α expression. We conclude that the sources for O2- formation and the relative importance of TNF-α in the pathophysiology of I/R-induced hepatocellular injury differ depending on the duration of ischemia.

AB - The objective of this study was to define the relationship among Kupffer cells, O2- production, and TNF-α expression in the pathophysiology of postischemic liver injury following short and long periods of ischemia. Using different forms of superoxide dismutase with varying circulating half-lives, a monoclonal antibody directed against mouse TNF-α, and NADPH oxidase-deficient mice, we found that 45 or 90 min of partial (70%) liver ischemia and 6 h of reperfusion (I/R) produced time-dependent increases in liver injury and TNF-α expression in the absence of neutrophil infiltration. Furthermore, we observed that hepatocellular injury induced by short periods of ischemia were not dependent on formation of TNF-α but were dependent on Kupffer cells and NADPH oxidase-independent production of O2-. However, liver injury induced by extended periods of ischemia appeared to require the presence of Kupffer cells, NADPH oxidase-derived O2-, and TNF-α expression. We conclude that the sources for O2- formation and the relative importance of TNF-α in the pathophysiology of I/R-induced hepatocellular injury differ depending on the duration of ischemia.

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KW - Reactive oxygen species

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Regulation of postischemic liver injury following different durations of ischemia

Abstract

Keywords

ASJC Scopus subject areas

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