2009
DOI: 10.1016/j.jss.2007.12.784
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Steatosis Reversibly Increases Hepatocyte Sensitivity to Hypoxia-Reoxygenation Injury

Abstract: BACKGROUND-Steatosis decreases survival of liver grafts after transplantation due to poorly understood mechanisms. We examined the effect of steatosis on the survival of liver grafts in a rat liver transplantation model and the viability of cultured rat hepatocytes after hypoxia and reoxygenation.

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Cited by 48 publications
(73 citation statements)
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“…Thus, it is conceivable to state that under the conditions of cold storage EPO might particularly protect the hepatic microvascular endothelium by its specific properties to enhance endothelial cell resistance. The exclusive responsiveness of steatotic livers to EPO may be attributed to their local environment, being characterized by increased hepatocyte sensitivity to hypoxia-reoxygenation injury compared with lean livers [56]. This proneness to hypoxia might in turn allow the steatotic liver to more efficiently respond to EPO as classic hypoxia-regulated growth factor.…”
Section: Discussionmentioning
confidence: 99%
“…Thus, it is conceivable to state that under the conditions of cold storage EPO might particularly protect the hepatic microvascular endothelium by its specific properties to enhance endothelial cell resistance. The exclusive responsiveness of steatotic livers to EPO may be attributed to their local environment, being characterized by increased hepatocyte sensitivity to hypoxia-reoxygenation injury compared with lean livers [56]. This proneness to hypoxia might in turn allow the steatotic liver to more efficiently respond to EPO as classic hypoxia-regulated growth factor.…”
Section: Discussionmentioning
confidence: 99%
“…Six studies measured levels of O 2 .-and steatotic livers were shown consistently to have increased levels of O 2 .-pre- [107] and post-IRI [23,63,66,69,75]. Interestingly, Nardo and colleagues [63] [32,47].…”
Section: Glutamate Dehydrogenase and Superoxidementioning
confidence: 97%
“…However, other enzymes such as xanthine oxidase (XOD), nicotinamide adenine dinucleotide phosphate-oxidase and monoamine oxidase [94,99] also [23,63,66,69,75,107]; c, [32,47]; d, [54,57]; e, [55,57]; f, [57]; g, [20,21,23 [87]. ONOO.-has been shown to irreversibly inhibit most components of the ETS including complex I-III [101] leading to impaired oxidative phosphorylation.…”
Section: Superoxide Production and Superoxide Dismutase Functionmentioning
confidence: 99%
“…61 On the other hand, the composition of hepatic lipids and particularly thromboxane A 2 levels are considered the principal modulators of I/R injury in the steatotic livers, while the size and morphology of lipid droplets are insignificant. 70 Other potential mechanisms that have been proposed include Kupffer cell dysfunction, 71 more lipid peroxidation, 72,73 more exuberant pro-inflammatory responses, including increased release of pro-inflammatory mediators such as TNF-α, 74 and impaired leukocyte adhesion. 75 Therefore, it is likely that the increased vulnerability of the steatotic livers to more I/R injury are multifactorial, and further experimental studies are required to elucidate the underlying mechanisms.…”
Section: Impact Of Steatosis On Ltmentioning
confidence: 99%