No abstract

Restoration of bile flow after 9-day cholestasis in rat liver normalized the content of lipid peroxidation products. The removal of the cholestatic factor after 12-day cholestasis was not followed by recovery of these parameters. We showed that measurement of serum concentration of lipid peroxidation products in patients with cholelithiasis during the preoperative period holds promise for selection of the optimum time for surgical treatment and prediction of the risk of postoperative complications.Cholestasis is often followed by liver damage. This clinical state is usually observed in cholelithiasis (CLT) or hepatoduodenal tumors due to mechanical obstruction of bile flow. Damage to the hepatic parenchyma during cholestasis is associated with toxic effects of bile components and mechanical pressure of dilated biliary ducts. However, removal of the cholestatic factor does not necessarily normalize liver function [11,12]. It is important to evaluate the period and type of surgical treatment and to develop new methods for the prediction and prevention of postoperative complications.Oxidative stress induces death of liver cells [6]. Cholestasis is accompanied by accumulation of lipid peroxidation (LPO) products in the liver. Hence, free radical oxidation of membrane lipids plays a major role in hepatocyte death [7,9]. However, little is known about the intensity and role of LPO in liver damage after restoration of bile flow.Here we studied LPO in rat liver after the removal of the cholestatic factor (ligation of the common bile duct). Besides this, we evaluated whether parameters of LPO in the blood of patients may be used to predict postoperative complications after surgical treatment for cholestasis. MATERIALS AND METHODSSubhepatic cholestasis in Wistar rats was induced by double ligation of the extrapancreatic segment in the common bile duct. The duct was dissected. A sealed polyethylene catheter was introduced into the proximal end of the common bile duct. Laparotomy was performed under brietal anesthesia (50 mg/kg intravenously). The duration of cholestasis was 9 and 12 days. Blood flow was restored by cutting off the end of an intraductal catheter. Liver samples were studied 3-18 days after bile flow restoration. The liver of intact and sham-operated animals (narcosis, laparotomy, and manipulations on the common bile duct without ligation and dissection) served as the control.

Changes in sphingomyelinase activity, tumor necrosis factor α expression, and level of lipid peroxidation products in the course of development of cholestatic liver injury have been studied. The same type phase shifts in the analyzed parameters were observed, which included a marked decrease at the early stages of cholestasis (days 3-6) and a pronounced increase at the later stages (days 12-16), i.e., under the conditions of developed pathology. There was a significant positive linear correlation between tumor necrosis factor α expression, sphingomyelinase activity, and lipid peroxidation intensity in cholestatic injury. We propose that detected changes may reflect the balance between the effects of the two major bile components-bilirubin, which is accumulated in the liver at the early stages of cholestasis, and bile acids, whose influence dominates at the later stages of pathologic process. Our results indicate that tumor necrosis factor α overexpression, sphingomyelin cycle activation, and lipid peroxidation intensification may cause apoptosis of hepatocytes at the late stages of cholestasis.