l-744832 has been researched along with Hyperlipidemias* in 1 studies
1 other study(ies) available for l-744832 and Hyperlipidemias
Article | Year |
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Pravastatin improves renal ischemia-reperfusion injury by inhibiting the mevalonate pathway.
Statins are known to lessen the severity of renal ischemia-reperfusion injury. The present study was undertaken to define the mechanism of renoprotective actions of statins using a mouse kidney injury model. Treatment of mice with pravastatin, a widely used statin, improved renal function after renal ischemia-reperfusion without lowering the plasma cholesterol level. Administration of pravastatin with mevalonate, a product of HMG-CoA reductase, eliminated renal protection suggesting an effect of pravastatin on mevalonate or its metabolism. In hypercholestrolemic apolipoprotein E knockout mice with reduced HMG-CoA reductase activity; the degree of injury was less severe than in control mice, however, there was no protective action of pravastatin on renal injury in the knockout mice. Treatment with a farnesyltransferase inhibitor (L-744832) mimicked pravastatin's protective effect but co-administration with the statin provided no additional protection. Both pravastatin and L-744832 inhibited the injury-induced increase in plasma IL-6 concentration to a similar extent. Our results suggest the protective effect of pravastatin on renal ischemia-reperfusion injury is mediated by inhibition of the mevalonate-isoprenoid pathway independent of its lipid lowering action. Topics: Acute Kidney Injury; Animals; Apolipoproteins E; Cholesterol; Creatinine; Enzyme Inhibitors; Farnesyltranstransferase; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Kidney; Male; Methionine; Mevalonic Acid; Mice; Mice, Inbred C57BL; Mice, Knockout; Pravastatin; Reperfusion Injury; Terpenes | 2008 |