title: Phosphodiesterase type 5 inhibition attenuates cyclosporine A induced nephrotoxicity in mice.
abstract: We investigated the renal protective effects of phophodiesterase type 5 (PDE5) inhibitors in mice with cyclosporine A (CyA; a calcineurin phosphatase inhibitor) induced nephrotoxicity. Fifty male mice were divided into five groups of 10. Group 1 received no treatment, group 2 received only saline orally, group 3 received 30 mg/kg/day CyA by subcutaneous injection, group 4 received only 30 mg/kg/day vardenafil orally, and group 5 received 30 mg/kg/day CyA by subcutaneous injection and 30 mg/kg/day vardenafil orally. At 28 days, platelet-derived growth factor A (PDGF-A) and C (PDGF-C), transforming growth factor-beta 1 (TGF-β1), cyclo-oxygenase 1 and 2 (COX-1 and COX-2), and P glycoprotein (Pgp) expression levels were measured in the renal tissues. In addition, expressions of COX-1 and COX-2 genes were determined using real-time PCR. PDE5 inhibitor administration ameliorated decreased PDGF-A and C, TGF-β1, COX-1 and -2, and Pgp expression levels by modulation of cyclic guanosine monophosphate (cGMP) activity in kidneys. The relative expressions of COX-1 and COX-2 genes to GAPDH revealed that the maximum increase was obtained in the group treated with CyA and vardenafil for both COX-1 and COX-2 genes. Our study revealed that long term oral treatment with vardenafil protects kidneys from CyA induced nephrotoxicity. We showed that long term oral treatment with PDE5 prevents pathological kidney changes caused by CyA induced nephrotoxicity.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Kirikkale University , 71450, Kirikkale.
authors.forename: D
authors.initials: D
authors.lastname: Essiz
authors.forename: M
authors.initials: M
authors.lastname: Sozmen
authors.forename: M
authors.initials: M
authors.lastname: Sudagidan
authors.forename: A K
authors.initials: AK
authors.lastname: Devrim
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016572:Cyclosporine / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D000069058:Vardenafil Dihydrochloride / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D058986:Phosphodiesterase 5 Inhibitors; D010982:Platelet-Derived Growth Factor; D053773:Transforming Growth Factor beta1; D000069058:Vardenafil Dihydrochloride; D016572:Cyclosporine; D011451:Prostaglandin-Endoperoxide Synthases; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases
keywords: cyclosporine A; immunohistochemistry; nephrotoxicity; phosphodiesterase type 5