title: Cilostazol attenuates gentamicin-induced nephrotoxicity in rats.
abstract: BACKGROUND
  Gentamycin is a widely used antibiotic. The nephrotoxic adverse effects of the drug may limit its use. Cilostazol, a phosphodiesterase III inhibitor, was reported to protect from renal oxidative stress. This work aimed to investigate the possible protective effect of cilostazol on gentamicin-induced nephrotoxicity and the possible underlying mechanisms.
  
  
  METHODS
  40 male albino rats were divided into 4 equal groups: (1) Control; (2) Cilostazol, 10mg/kg, p.o.; (3) Gentamicin, 80 mg/kg, i.p.; (4) Gentamicin 80 mg/kg, i.p. along with cilostazol 10mg/kg, p.o. All drugs were administered once daily for 8 days. On 9th day blood samples were collected for the estimation of creatinine, urea and uric acid in serum. Then the rats were sacrificed and kidneys were removed for light and electron microscope studies. Moreover, reduced glutathione (GSH) and malondialdehyde (MDA) levels as well as catalase (CAT) and superoxide dismutase (SOD) activities were determined in renal tissues.
  
  
  RESULTS
  Gentamicin elevated the serum levels of creatinine, urea and uric acid as well as the MDA level in the renal tissue, while it decreased CAT, SOD activities and GSH levels as well as produced degenerative changes in glomeruli and tubules associated with increased expression of apoptotic markers and decreased expression of anti-apoptotic markers. Administration of cilostazol decreased urea, creatinine, uric acid and MDA levels while increased CAT and SOD activities and GSH levels as well as ameliorated the histopathological changes in relation to gentamicin group.
  
  
  CONCLUSIONS
  Cilostazol protected rats from gentamicin-induced nephrotoxicity possibly, in part through its antioxidant and anti-apoptotic activity.
authors.affiliation: Clinical Pharmacology Department, Faculty of Medicine, Zagazig University, Egypt.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Abdelsameea
authors.affiliation: Clinical Pharmacology Department, Faculty of Medicine, Zagazig University, Egypt.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Mohamed
authors.affiliation: Histology & Cell Biology department, Faculty of Medicine, Zagazig University, Egypt. Electronic address: mona_amer@rocketmail.com.
authors.forename: Mona G
authors.initials: MG
authors.lastname: Amer
authors.affiliation: Medical Biochemistry, Faculty of Medicine, Zagazig University, Egypt.
authors.forename: Shahera M
authors.initials: SM
authors.lastname: Attia
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D002374:Catalase / Q000378:metabolism; D000077407:Cilostazol; D005839:Gentamicins / Q000633:toxicity*; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D007677:Kidney Function Tests; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008854:Microscopy, Electron; D018384:Oxidative Stress / Q000187:drug effects*; D058987:Phosphodiesterase 3 Inhibitors / Q000494:pharmacology*; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D058987:Phosphodiesterase 3 Inhibitors; D013777:Tetrazoles; D002374:Catalase; D013482:Superoxide Dismutase; D000077407:Cilostazol
keywords: Apoptosis; Cilostazol; Gentamicin; Nephrotoxicity; Ultrastructure