title: Amelioration of cyclosporine induced nephrotoxicity by dipeptidyl peptidase inhibitor vildagliptin.
abstract: Cyclosporine A (CsA) is an immunosuppressive drug used in organ transplantation and autoimmune diseases but its clinical uses may be limited due to its dose-related nephrotoxicity. This study was carried out to evaluate the possible protective effects of vildagliptin (VLD) against CsA-induced nephrotoxicity in rats. Animals were divided into four groups treated as follows: control group (CsA & VLD vehicle); VLD group (10mg/kg/day, orally); CsA group (20mg/kg in sunflower oil, S.C.); and CsA-VLD group (CsA &VLD). Induced nephrotoxicity was evidenced by a significant elevation of serum creatinine, blood urea nitrogen (BUN), lactate dehydrogenase (LDH) and urinary micro total proteins (MTP), while serum albumin and urinary creatinine clearance were significantly decreased compared to the control group. Moreover, renal dysfunction was further confirmed by a significant increase in renal lipid peroxide that was measured as renal malondialdehyde (MDA). Renal reduced glutathione (GSH) and superoxide dismutase (SOD) were significantly decreased. Nephrotoxicity was further confirmed by renal tissue histopathology. Also, a high protein expression of Bax with decreased Bcl-2 was revealed in the renal tissue of the CsA treated group. Administration of VLD significantly ameliorated the nephrotoxic effects of CsA suggesting antioxidant, anti-inflammatory and anti-apoptotic benefits of VLD in CsA-induced nephrotoxicity.
authors.affiliation: Faculty of Medicine, Cairo University, Egypt; College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia. Electronic address: hayamatya@hotmail.com.
authors.forename: Hayam
authors.initials: H
authors.lastname: Ateyya
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000009:adverse effects*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000097:blood; D015227:Lipid Peroxidation; D008297:Male; D009570:Nitriles / Q000627:therapeutic use; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011759:Pyrrolidines / Q000627:therapeutic use; D017208:Rats, Wistar; D012709:Serum Albumin / Q000032:analysis; D013482:Superoxide Dismutase / Q000378:metabolism; D000077597:Vildagliptin; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007166:Immunosuppressive Agents; D009570:Nitriles; D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D011759:Pyrrolidines; D012709:Serum Albumin; D051028:bcl-2-Associated X Protein; D016572:Cyclosporine; D003404:Creatinine; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D005978:Glutathione; D000077597:Vildagliptin; D000218:Adamantane
keywords: Cyclosporine; Inflammation and apoptosis; Nephrotoxicity; Vildagliptin