F₂-isoprostanes and the kidney

PGF₂-like compounds are formed in abundance in vivo by the free radical-induced peroxidation of arachidonic acid, independent of the cyclooxygenase enzyme. These compounds are collectively referred to as F₂- isoprostanes because of their structural similarity to cyclooxygenase- derived PGF(2α). Certain findings suggest a potential role for isoprostanes as mediators of some of the adverse sequelae of ischemia-reperfusion injury to kidney. Recent evidence also suggests a potentially important role for isoprostanes in the pathogenesis of hepatorenal syndrome. Cell culture studies suggest that cisplatin-induced LLC-PK1 cell injury may be attended by increased isoprostane production through a mechanism involving thiol depletion. Another area in which a role for free radical-induced lipid peroxidation and F₂-isoprostanes has been suggested is in the pathogenesis of ciclosporin (CSA)-induced renal toxicity. A recent study also suggests that enhanced formation renal F₂-isoprostanes may be relevant to the progressive reduction in renal blood flow demonstrable in aging kidneys. This emerging evidence suggests that further studies are warranted to determine the importance of F₂-isoprostanes in human renal diseases characterized by renal vasoconstriction, such as renal ischemia, hepatorenal syndrome, renal senescence and toxic nephropathies.