New Mechanistic Insights in the Development of Diabetic Nephropathy: Role of Cytochromes P450 and Their Metabolites

Diabetic Nephropathy (DN), a major complication of diabetes, is characterized by hypertrophy, extracellular matrix accumulation, fibrosis and proteinuria leading to loss of renal function. However, the mechanisms leading to kidney injury is not well defined. Arachidonic acid is primarily metabolized by Cytochromep-450 (CYP) enzymes to 20-Hydroxyeicosatetraenoic acid (20-HETE) and Epoxyeicosatrienoic acids (EETs) and these compounds have a role in renal physiology and pathophysiology. Recent studies show that the production of EETs and 20-HETE is altered in diabetes. More interestingly, we and others have established a link between the alteration in the production of 20-HETE and EETs and the onset and development of diabetic-induced kidney injury, and that these cytochromes P450 metabolites of arachidonic acid contribute to the changes in renal structure and function seen in diabetic nephropathy. All the results described in this review suggest that the drugs that modify the formation and/or actions of EETs and 20-HETE may have therapeutic benefits for diabetic nephropathy treatment.