title: Melatonin can attenuate ciprofloxacin induced nephrotoxicity: Involvement of nitric oxide and TNF-α.
abstract: BACKGROUND
  Ciprofloxacin is a synthetic broad-spectrum antimicrobial agent of fluoroquinolone family. The aim of our investigation was to evaluate the role of oxidative damage and inflammation in nephrotoxic potential of Ciprofloxacin and protective effects of melatonin against its nephrotoxicity in male Wistar rats.
  
  
  METHODS
  The animals were divided into six groups: Control, ciprofloxacin (100mg/kg/day, i.p), ciprofloxacin with three doses (2.5, 5 and 10mg/kg/day) of melatonin and a group which received ciprofloxacin (100mg/kg/day) plus vitamin E (100mg/kg/day) for 8 consecutive days. 24h after last injection, the animals were euthanized and kidney tissues were separated. Finally reactive oxygen species, glutathione content, lipid peroxidation, protein carbonyl, nitric oxide and TNF-α were evaluated. Also, pathological examination and measuring of kidney biochemical markers (BUN and Cr) were done.
  
  
  RESULTS
  The administration of ciprofloxacin for 8days resulted in significant increase (P<0.01) in kidney biomarkers (BUN and Cr) and pathological changes. Also, Oxidative stress was evident in ciprofloxacin group by significantly (p<0.001) increased reactive oxygen species, lipid peroxidation and protein carbonyl level and decreased glutathione content (p<0.001). Increased in inflammation process was shown by increase in NO and TNF-α (P<0.001). Administration of melatonin was able to protect against deterioration in nephrotoxic markers and suppressed the increase in oxidative stress and inflammatory markers.
  
  
  CONCLUSIONS
  Our study showed the critical role of oxidative damage and inflammation in ciprofloxacin-induced nephrotoxicity that markedly inhibited by administration of melatonin. So, melatonin can be suggested for prevention of ciprofloxacin-induced nephrotoxicity.
authors: Department of Toxicology/Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
authors: Fatemeh
authors: F
authors: Shaki
authors: Students Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
authors: Sorour
authors: S
authors: Ashari
authors: Pharmaceutical Sciences Research Center and Department of Toxicology/Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address: n.ahangar@mazums.ac.ir.
authors: Nematollah
authors: N
authors: Ahangar
mesh_terms: D000818:Animals; D002939:Ciprofloxacin / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D007677:Kidney Function Tests; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism*; D050050:Protein Carbonylation / Q000187:drug effects; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D002939:Ciprofloxacin; D003404:Creatinine; D005978:Glutathione; D008550:Melatonin
keywords: Ciprofloxacin; Melatonin; NO; Nephrotoxicity; Oxidative stress; TNF-α