title: The protective effect of losartan in the nephropathy of the diabetic rat includes the control of monoamine oxidase type A activity.
abstract: Monoamine oxidase activity (MAO-A and B) levels, as intracellular source of reactive oxygen species, might increase in diabetic nephropathy (DN) contributing to reduce dopamine levels and to unbalance kidney redox state. We explored the hypothesis that beneficial effects of losartan, an angiotensin-II type 1 receptor (AT1) blocker, in DN included the control of MAO activity levels. In kidneys of normoglycemic and diabetic, streptozotocin-injected (55 mg/kg) rats, treated or untreated with losartan, an AT1 antagonist (20mg/kg/day in the drinking water), we investigated MAO activity radiochemically and antioxidant enzymes including catalase, aldehyde dehydrogenase and superoxide dysmuthase spectrophotometrically. In addition, we also evaluated malondialdehyde and carbonylated protein levels spectrophotometrically as indexes of oxidative attack to lipids and proteins. Diabetic rats showed signs of nephropathy, including renal hypertrophy, proteinuria, high acethylglucosaminidase and γ-glutamyltranspeptidase urinary levels. In diabetic kidneys, MAO-A and catalase activities as well as malondialdehyde levels, were found significantly higher than in normoglycemic ones. Interestingly, in diabetic kidneys, MAO-A activity correlated not only with catalase but also with γ-glutamyltranspeptidase urinary levels. Our results indicate that the control of MAO-A activity is to be included amongst the mechanisms of protection afforded by losartan in DN. In fact, the prevention of MAO-A raise might increase dopamine availability and, as suggested by the correlation with γ-GGT, reduce oxidative attack to tubular cells.
authors: Department of Pharmacology, University of Florence, Viale G Pieraccini 6, 50139 Florence, Italy.
authors: Maria Elena
authors: ME
authors: Manni
authors: Elisabetta
authors: E
authors: Bigagli
authors: Maura
authors: M
authors: Lodovici
authors: Marina
authors: M
authors: Zazzeri
authors: Laura
authors: L
authors: Raimondi
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002374:Catalase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use*; D008315:Malondialdehyde / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D020011:Protective Agents; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase; D000444:Aldehyde Dehydrogenase; D008995:Monoamine Oxidase; D019808:Losartan