Ischemic Preconditioning Attenuates Morphological and Biochemical Changes in Hepatic Ischemia/Reperfusion in Rats

Abstract

Objective: Ischemic preconditioning (IPC) has been gradually introduced into clinical liver surgery and transplantation in recent years. However, the protective effects of IPC on hepatic warm ischemia/reperfusion (I/R) injury and the potential mechanisms involved are not fully understood. We aimed to evaluate whether the reduction of apoptotic sinusoidal endothelial cells (SECs), induced by IPC, contributes to its protective effect. Methods: Male Wistar rats were randomized into three experimental groups: the continuous clamping group underwent 60 min of 70% hepatic ischemia; the IPC group received 10 min ischemia followed by 10 min reperfusion prior to ischemia, and the sham control (sham) underwent a sham operation without ischemia. Hepatocyte and SEC apoptosis, liver necrotic areas and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid, tumor necrosis factor, myeloperoxidase (MPO) and malondialdehyde were determined. Expression of cysteine-aspartic acid protease-3 (caspase-3) in hepatocytes and SECs was also investigated. Furthermore, the hepatic leukocyte infiltration was assessed by intravital fluorescence microscopy. Results: IPC exhibited a significant alleviation of their postischemic liver function. Serum AST, ALT and tissue MPO were significantly decreased by IPC, and the degree of hepatocyte and SEC apoptosis was significantly inhibited, as shown by the decreased numbers of adherent leukocytes. Conclusions: IPC attenuates hepatic I/R injury by the reduction of leukocyte infiltration, the reduction hepatic enzymatic leakage and the depression of apoptotic cells. SECs are more sensitive to apoptosis induced by warm I/R injury compared to hepatocytes.

From Rapid to Delayed and Remote Postconditioning: The Evolving Concept of Ischemic Postconditioning in Brain Ischemia

“…In addition to myocardium, the phenomenon of ischemic preconditioning for acute ischemia–reperfusion injury has been reproduced in other organs including the liver[12], kidney [13]and brain[4]. Similar to cardiac preconditioning, the development of a tolerant brain appears to result from the activation of endogenous mechanisms of protection against brain injuries.…”

Assessment of effects of IR and IPC on activities of cytochrome P450 isozymes in rats by a five-drug cocktail approach

“…IR injury can result in significant liver injury 17 . IPC has been shown to protect organs against subsequent sustained ischemia.…”

Immediately transcripted genes in various hepatic ischemia models

“…Cleavage of genomic DNA during apoptosis results in DNA strand breaks that can be identified by labeling free 38-hydroxyl ends with modified nucleotides in an enzymatic reaction involving terminal deoxynucleotidyl transferase [14-16]. The prepared paraffin-embedded sections were stained using a commercially available kit (Apop Tag Peroxidase In Situ Apoptosis Detection Kit S7100; Chemicon International Inc., Billerica, MA, USA) according to the manufacturer's protocols.…”