Involvement of renal cytochromes P450 and arachidonic acid metabolites in diabetic nephropathy

摘要: Diabetic nephropathy (DN) is one of the most serious complications type I and II diabetes. DN characterized by hyperfiltration, hypertrophy, extracellular matrix accumulation, proteinuria. This advances into renal fibrosis loss function. Reactive oxygen species (ROS) TGF-beta have been implicated in pathogenesis diabetic nephropathy. Early stages are also associated with alterations sodium handling as well hypertension; both processes linked involvement arachidonic acid (AA) metabolites, 20-hydroxyeicosatetraenoic (20-HETE, produced cytochrome P450-4a, (CYP4A) epoxyeicosatrienoic acids (EETs). Indeed, metabolism AA increased a rat model In this study, we demonstrate that rats streptozotocin-induced diabetes 1 month duration develop hypertrophy fibronectin TGF-beta1 expression/cortical levels concomitant an increase CYP4A expression 20 HETE production. These results were paralleled reactive production NADPH oxidase activity. Treatment HET0016, selective inhibitor CYP 4A, prevented all these changes. Our suggest diabetes-induced induction 20-HETE could be major pathophysiological mechanism leading to activation ROS through dependent pathway thus resulting pathology. Inhibitors important therapeutic potential treatment