Investigation of the effects of etanercept on hepatic cells and apoptosis in rats with obstructive jaundice

At any level of the bile ducts, as a result of the partial or complete occlusion concluding of any disease, obstructive jaundice occurs by the inhibition of bile flow. One of the leading causes of morbidity and mortality in patients with cholestasis is the development of infectious complications such as sepsis(1). If there is no bile secretion to the intestine, substances that excreted from the bile may accumulate at blood. As a result of the cholestasis, pathologic conditions such as reticuloendothelial dysfunction, deterioration of structure and function of intestinal mucosa, immunosuppression, oxidative damage in the intestinal wall, bacteraemia and endotoxemia occur (2, 3). In cholestasis, stasis secondary liver damage occurs. At cholestatic jaundice, in addition to infectious pathogens, cellular stress and damage can trigger release of endogenous molecules known as alarming molecules. As a result, in the host, the immune system response is initiatedand the Tool like receptor molecules (TLR1,2,4,6,7,9) are released. HMGB1 (High mobility group box-1) protein was reported to be an important molecule in endotoxin-related deaths in mice for the first time in 1999. For this reason, it has been suggested that HMGB1 molecule may be important in the development of cholestatic liver disease. In their study, Huang et al. investigated HMGB1 expression and TLR activation of glucocorticoids in obstructive jaundice rats.They measured HMGB1 levels in plazma and found them to be high.When they administered glucocorticoid therapy to rats, they found that HMGB1 protein expression and serum levels were decreased in the liver. Again, they reported that TLR2 and TLR4 expressions are associated with the HMGB1 signal, and that glucocorticoid therapy is more effective at TLR4 levels compared to TLR2 levels. From these findings, they found that HMGB1, TLR4 axis plays an important role in hepatic damage in obstructive jaundice (9). In liver, inoculation of transplanted cells in cell therapy is very critical, after activation of neutrophils or Kupffer cells, most of the transplanted cells are rapidly cleared from the liver by the proinflammatory cytokines / chemokines / receptors by the liver sinusoids. In their study, Wiswanathan et al. investigated the etanerceptin, a TNF α antagonist effect on hepatocyte transplantation of rat, in cell-transplantation-induced hepatic inflammation. There was an increase in the quantities of many cytokines/chemokines/receptors after cell transplantation, whereas prior to cell transplantation, they reported that the use of etarnercept normalized this response. Furthermore, they reported that etanerceptine significantly reduced the release of intrahepatic secretory cytokines [such as High Mobility Group Box Protein 1 (HMGB1)] induced by cell transplantation. Etanerceptin has reported that this effect reduces neutrophil activation associated with cell transplantation, but does not affect Kupffer cells. It has been reported that the rejection of cells transplanted in animals treated with high doses of etanerceptin (7). In each group, which had 10 animals, 3 groups were formed for experiment, control and sham group. The Sham group was created to standardize the study of anaesthetics and the possible risks compared to other groups. Group I (n = 10): Sham Group, after the laparotomy, the main bile duct of animals was exposed and the bell was closed, followed by feeding the animal with standard feed and water for 7 days. Group II (n = 10): Control Group after laparotomy, the main bile ducts of animals were exposed and bonded with 4/0 silk, and the animals fed were given standard feed and water for 7 days. Group III (n = 10): Experimental Group after laparotomy, the main bile ducts of animals were exposed and bonded with 4/4 silk, and the animals fed were given standard feed and water for 7 days. The animals in this group were given intraperitoneal etanercept at a dose of 2 mg / kg for 7 days starting from the day when they were biliary duct. Afterwards, liver and blood samples were taken from the rats and the rats were sacrificed. We investigated the effects of etanerceptin for anti-inflammatory and antiapoptotic purposes in the treatment of obstructive jaundice. Biochemically and histopathologically, when we examine our study data; we think that there is no anti-inflammatory, antiapoptotic effect of etanerceptin on obstructive jaundice therapy, but it may have effects on DNA damage at cellular level. At the histopathological level, we also observed that this effect was not in the short term.