Abstract
A major consequence of obstructive jaundice (OJ) in clinical practice is the development of severe liver injury, and at present, no effective treatments have been developed to protect against it. Preconditioning with damage-associated molecular pattern (DAMP) molecules has been demonstrated to protect multiple organs from injury, and histones have been recently identified as DAMP molecules. The aim of the present study was to investigate the protective effect of histone preconditioning against OJ-induced liver injury in rats and the involvement of Toll-like receptors. Rats were administered histone proteins (200 μg/kg; 1 ml) or physiological saline (1 ml) intraperitoneally 24 h prior to being subjected to bile duct ligation (BDL). The serum levels of liver enzymes and bilirubin, as well as the histopathology were analyzed. The mRNA expression of interleukin-6 (IL-6) in the liver tissue was analyzed using quantitative polymerase chain reaction. BDL in the control group caused severe OJ-induced liver injury, as indicated by the significantly elevated levels of liver enzymes and mRNA levels of IL-6, and confirmed by histopathological alterations. However, histone preconditioning significantly ameliorated the OJ-induced liver injury caused by BDL, as shown by an improvement in the levels of liver enzymes, a suppression of IL-6 production, as well as histopathological alterations. Therefore, these results suggested that histone preconditioning is able to protect against OJ-induced liver injury in rats.
Highlights
Obstructive jaundice (OJ) is a common pathophysiological process that occurs in numerous clinical conditions, including gallstones, stricture of the bile duct and pancreatic cancer.Key words: histone, precondition, obstructive jaundice, liver injurySurgical or interventional decompression is the main treatment strategy for OJ patients [1]
Biliary intervention has been demonstrated to augment inflammatory cell infiltration and aggravate OJ‐induced liver injury [22,23]
The present study demonstrated that liver injury in animals in the HPC group was significantly ameliorated by histone preconditioning compared with the control group, as indicated by significant differences in the degree of necroinflammation and a decrease in the number of neutrophils infiltrating into the liver tissue
Summary
Obstructive jaundice (OJ) is a common pathophysiological process that occurs in numerous clinical conditions, including gallstones, stricture of the bile duct and pancreatic cancer. Surgical or interventional decompression is the main treatment strategy for OJ patients [1]. In the treatment of OJ patients, severe complications may occur in surgical or interventional decompression. The procedure of decompression itself is not enough to prevent the complications. One of the major consequences of OJ is the development of severe liver injury [2]. The mechanisms responsible for the pathogenesis of OJ‐induced liver injury remain largely unknown, inflammatory cell infiltration, microvascular perfusion failure and Toll‐like receptor (TLR) activation are reported to be involved [3,4]. There are no effective treatments to protect against OJ‐induced liver injury, novel therapeutic strategies are urgently required
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