Influence Of Ezetimibe Research Articles

Influence of ezetimibe on ADMA-DDAH-NO pathway in rat liver subjected to partial ischemia followed by global reperfusion

BackgroundWe evaluated effect of ezetimibe on selected parameters determining NO level in rat liver subjected to ischemiareperfusion (IR). MethodsRats received ezetimibe (5mg/kg) (groups E0 and EIR) or saline solution (groups C0 and CIR) intragastrically for 21 days. Then, the livers of CIR and EIR underwent ischemia (60min) and reperfusion (4h). Blood samples were obtained before surgery to estimate activities of aminotransferases, and just before ischemia and during reperfusion to estimate asymmetric and symmetric dimethylarginine (ADMA, SDMA) and arginine (Arg) levels. After IR, dimethylarginine dimethylaminohydrolase (DDAH) activity and endothelial nitric oxide synthase (eNOS) protein concentration were measured in liver homogenates.DDAHand protein arginine methyltransferase (PRMT) mRNA were quantified by real-time PCR in liver tissue samples. ResultsIn CIR, the ADMA level was significantly higher compared to all other groups in 30min and to E0 group in 120min of reperfusion. In EIR, ADMAwas low, compared to non-ischemic groups. At 30 and 120min of reperfusion, in non-ischemic groups the level of Arg and Arg/ADMAratio were significantly higher than in ischemic groups and E0 was the group with the highest levels of those parameters of all. In CIR, eNOS protein concentration was significantly lower than in ezetimibe-treated groups. Activity of DDAH was significantly higher in E0 than in non-treated groups. In ischemic groups, DDAH mRNA expression was significantly higher than in non-ischemic ones and PRMT mRNA expression was significantly higher in C0 than in all other groups. ConclusionsInfluence of ezetimibe on ADMA/DDAH/NO pathway demonstrated in this work may suggest protective properties of this drug on rat livers injured by IR and, to a lower extent, on livers non-subjected to IR.

Ezetimibe ameliorates hepatic steatosis but potentiates hepatic oxidative stress

INTRODUCTION: The pandemic of diet-induced obesity has resulted in an increased incidence of nonalcoholic fatty liver disease (NAFLD). Increased lipid oxidation and consequentially oxidative stress catalyze the progression of NAFLD to nonalcoholic steatohepatitis (NASH) and potentially cirrhosis and cancer. Ezetimibe, which inhibits intestinal fat absorption, has been shown to decrease visceral fat accumulation. However, the influence of ezetimibe on hepatic lipids and oxidative stress on a high fat diet are unknown. Therefore, we tested the hypothesis that ezetimibe would ameliorate NAFLD by inhibiting lipid accumulation and oxidative stress in the liver.

Ezetimibe ameliorates cholecystosteatosis

Cholecystosteatosis is the accumulation of gallbladder wall fats leading to decreased gallbladder emptying. Ezetimibe inhibits intestinal fat absorption and prevents murine gallstone formation. However, the influence of ezetimibe on gallbladder emptying and cholecystosteatosis has not been studied. Therefore, we tested the hypothesis that ezetimibe would improve gallbladder motility by preventing the buildup of fats in the gallbladder wall. Forty lean female mice were fed either a control diet or a lithogenic diet for 6 weeks. Half of the mice on each diet received ezetimibe. At 11 weeks of age, all mice were fasted overnight and underwent gallbladder ultrasonography to determine ejection fraction. One week later, the mice were fasted and underwent cholecystectomy. Bile was examined for cholesterol crystals. The gallbladders were snap-frozen for lipid analysis. The lithogenic diet significantly (P < 0.05) increased serum cholesterol, biliary crystals, gallbladder wall cholesterol and cholesterol/phospholipid ratio, and decreased gallbladder ejection fraction. All of these abnormalities were reversed (P < 0.05) by the addition of ezetimibe to the diet. These data suggest that ezetimibe lowers serum cholesterol, prevents biliary crystals, and normalizes gallbladder wall fat and function. We conclude that ezetimibe ameliorates cholecystosteatosis and may be an effective agent for gallstone prevention.