Autophagy and liver ischemia-reperfusion injury.

Liver ischemia-reperfusion (I-R) injury occurs during liver resection, liver transplantation, and hemorrhagic shock. The main mode of liver cell death after warm and/or cold liver I-R is necrosis, but other modes of cell death, as apoptosis and autophagy, are also involved. Autophagy is an intracellular self-digesting pathway responsible for removal of long-lived proteins, damaged organelles, and malformed proteins during biosynthesis by lysosomes.

Ischemia-Reperfusion Injury and Ischemic-Type Biliary Lesions following Liver Transplantation.

Ischemia-reperfusion (I-R) injury after liver transplantation (LT) induces intra- and/or extrahepatic nonanastomotic ischemic-type biliary lesions (ITBLs). Subsequent bile duct stricture is a significant cause of morbidity and even mortality in patients who underwent LT. Although the pathogenesis of ITBLs is multifactorial, there are three main interconnected mechanisms responsible for their formation: cold and warm I-R injury, injury induced by cytotoxic bile salts, and immunological-mediated injury.

Tyrosine phosphorylation of insulin receptor substrates during ischemia/reperfusion-induced apoptosis in rat liver.

Background: Phosphoregulation of signal transduction pathways is a complex series of reactions that may modulate the cellular response to ischemia-reperfusion (I-R). The aim of this study was to evaluate the effect of normothermic liver I/R-induced apoptosis on phosphorylation and activation of signal proteins in tyrosine kinase pathways.

Materials And Methods: In rats, a segmental normothermic ischemia of the liver was induced for 120 min.

Pentoxifylline inhibits liver expression of tumor necrosis factor alpha mRNA following normothermic ischemia-reperfusion.

Background: Pentoxifylline (PTX) has been shown to reduce hepatic injury after normothermic ischemia and reperfusion (I-R) in rat liver.

Aim: The aim of this study was to evaluate the effects of PTX on liver expression of tumor necrosis factor alpha (TNFalpha) mRNA following normothermic liver I-R.

Materials And Methods: A segmental normothermic ischemia of the liver was induced in male Lewis rats by occluding the blood vessels including the bile duct to the median and left lateral lobes for 90 min.

Effect of caspase inhibition on thymic apoptosis in hemorrhagic shock.

In hemorrhagic shock (HS) an increased thymic apoptosis (TA) was described. The aim of this study was to evaluate the effect of administration of the caspase inhibitor N-benzyloxy-carbonil-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK) during the resuscitation phase on TA, organ dysfunctions, and tumor necrosis factor (TNF)-alpha release in HS. Forty rats were randomly assigned to four groups: no HS/resuscitation (sham); HS/resuscitation with shed blood and normal saline (control); HS/resuscitation with shed blood and phosphate-buffered solution (PBS) (vehicle); and HS/resuscitation with shed blood and Z-VAD-FMK (inhibitor).

Fas ligand expression following normothermic liver ischemia-reperfusion.

Background: The aim of this study was to evaluate the role of the pro-apoptotic molecule Fas Ligand (FasL) in 120 min normothermic ischemia-reperfusion (I-R) induced apoptosis in rat liver treated or not with Z-Asp-cmk caspase inhibitor.

Materials And Methods: Rats were divided into two groups: group 1, control, PBS administration; group 2, Z-Asp-cmk treatment. Z-Asp-cmk was injected intravenously, 2 min before induction of 120 min of normothermic liver ischemia.

Rat liver ischemia-reperfusion-induced apoptosis and necrosis are decreased by FK506 pretreatment.

The aim of this study was to demonstrate that tacrolimus (FK506) has a hepatoprotective effect by reducing ischemia-reperfusion-induced apoptosis and necrosis, both of which lead to post-surgical liver dysfunction. An ischemia-reperfusion model and primary cultured rat hepatocytes subjected to hypoxic and reoxygenation phases, mimicking the surgical process, were used. c-Jun N-terminal kinase 1/stress-activated protein kinase 1 (JNK1/SAPK1) activation leads to caspase 3 activation, a trigger of apoptosis.

Consequences of adrenalectomy on small intestine trophic parameters in aged and young rats: evidence of defective adaptation by aging and lack of corticoids.

Previous study pointed to an important role of adrenals and glucocorticoids in the trophic status of the adult small intestine mucosa, with possible implications during stress events. Small intestine morphological and biochemical consequences of 10-day bilateral adrenalectomy and also sham-related laparotomy were determined in 23-month-old Sprague-Dawley rats. As described in young rats, adrenalectomy in old rats leads to partial atrophy and disorganization of the proximal small intestine epithelium, with an increase in the number of Paneth cells and reduced crypt cell proliferation.

Diltiazem reduces apoptosis in rat hepatocytes subjected to warm hypoxia-reoxygenation.

Interruption of hepatic blood flow is necessary in surgery, but the liver is sensitive to ischemia and reperfusion. Hypoxia induces an increase in intracellular calcium concentration. In previous studies, we have shown that hypoxia-reoxygenation (H/R) increased calcium influx and induced JNK(1)/SAPK(1) activation which was involved in the triggering of apoptosis.

Rat liver injury after normothermic ischemia is prevented by a phosphinic matrix metalloproteinase inhibitor.

Hepatic ischemia occurs in liver transplantation, hemodynamic or cardiogenic shock, and liver resection associated with trauma or tumor. Ischemia/reperfusion (I/R) injury results in microcirculation failure followed by apoptosis and necrosis. Matrix metalloproteinases (MMPs) are involved in many physiological and pathological processes, but their expression and function during liver I/R remains poorly documented.