title: The Protective Effect of Apocynin on Cyclosporine A-Induced Hypertension and Nephrotoxicity in Rats.
abstract: Cyclosporine A (CsA) is the prototype of immunosuppressant drugs that has provided new perspectives in human and veterinary medicine to prevent organ transplant rejection and to treat certain autoimmune diseases and dermatologic diseases. Unfortunately, the treatment with CSA is often limited by severe adverse effects such as hypertension and nephrotoxicity. Some data suggest that reactive oxygen species (ROS) and the oxidative stress play an important role in its pathogenesis, in particular the superoxide (O2 (-)) that is the most powerful free radical generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase present mainly in the kidney. The present study has been designed to investigate the role of Apocynin a selective inhibitor of NADPH oxidase activity on cyclosporine-induced adverse effect. In this study, we have evaluated the effect of CsA, used alone or in association with Apocynin on blood pressure (BP), on glomerular filtration rate (GFR), on absoluted fluid reabsorption (Jv) in proximal tubule (PT), on O2 (-) concentration, and on nitric oxide (NO) production. We have demonstrated that CsA administration increases superoxide concentration in the aorta, decreases the NO concentration, reduces GFR and the Jv in PT, and induces a significant increase in BP. Moreover, we have shown that Apocynin treatment restores these hemodynamic alterations, as well as NO and superoxide productions. In conclusion, the reported data indicate that CsA induced nephrotoxicity and hypertension are related to NADPH oxidase activity, in fact Apocynin protects the kidney function and BP from toxic effects induced by CsA through the inhibition of NADPH oxidase activity.
authors.affiliation: Department of Veterinary Medicine and Animal Productions, University of Naples "Federico II,", Naples, 80137, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ciarcia
authors.affiliation: Department of Veterinary Medicine and Animal Productions, University of Naples "Federico II,", Naples, 80137, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Damiano
authors.affiliation: Department of Veterinary Medicine and Animal Productions, University of Naples "Federico II,", Naples, 80137, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Florio
authors.affiliation: Department of Nephrology, Second University of Naples, Naples, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Spagnuolo
authors.affiliation: Department of Nephrology, Second University of Naples, Naples, Italy.
authors.forename: Enza
authors.initials: E
authors.lastname: Zacchia
authors.affiliation: Department of Veterinary Medicine and Animal Productions, University of Naples "Federico II,", Naples, 80137, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Squillacioti
authors.affiliation: Department of Veterinary Medicine and Animal Productions, University of Naples "Federico II,", Naples, 80137, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Mirabella
authors.affiliation: Department of Veterinary Medicine and Animal Productions, University of Naples "Federico II,", Naples, 80137, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Florio
authors.affiliation: Department of Veterinary Medicine and Animal Productions, University of Naples "Federico II,", Naples, 80137, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: Pagnini
authors.affiliation: AORN Dei Colli Monaldi UOC, Oncology, Naples, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Garofano
authors.affiliation: Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
authors.forename: Maria Sole
authors.initials: MS
authors.lastname: Polito
authors.affiliation: Department of Nephrology, Second University of Naples, Naples, Italy.
authors.forename: Giovambattista
authors.initials: G
authors.lastname: Capasso
authors.affiliation: Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.|Sbarro Institute for Cancer Research and Molecular Medicine, Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania.
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
mesh_terms: D000098:Acetophenones / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016572:Cyclosporine / Q000009:adverse effects*; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006973:Hypertension / Q000209:etiology / Q000517:prevention & control*; D007674:Kidney Diseases / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000098:Acetophenones; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D016572:Cyclosporine; C056165:acetovanillone; D019255:NADPH Oxidases
keywords: APOCYNIN; CYCLOSPORINE A; NITRIC OXIDE; REACTIVE OXYGEN SPECIES