title: Protective effect of ketamine against hemorrhagic cystitis in rats receiving ifosfamide.
abstract: OBJECTIVE
  To investigate the possible protective effect of a single dose of ketamine and the synergistic effect between ketamine and 2-mercaptoethane sulfonate (mesna) against ifosfamide-induced hemorrhagic cystitis.
  
  
  METHODS
  35 adult female wistar rats were divided into five groups and pretreated with ketamine at 10 mg/kg and/or mesna 400 mg/kg 30 minutes before intraperitoneal injection of IFS (400 mg/kg) or with saline (control group). Hemorrhagic cystitis was evaluated 24 hours after IFS injection according to bladder wet weight (BWW), and microscopic changes, i.e. edema, hemorrhage, cellular infiltration, and urothelial desquamation. The markers of oxidative damage including nitric oxide (NO) and malondialdehyde (MDA) levels and the expressions of tumor necrosis factor alpha (TNF-α), interleukin 1-beta (IL-1β), inducible nitric oxide synthase (i-NOS) and endothelial nitric oxide synthase (e-NOS) were also assayed in the bladder tissues.
  
  
  RESULTS
  Pretreatment with ketamine alone or ketamine in combination with mesna reduced the IFS-induced increase of BWW (58,47% and 63,33%, respectively, P < 0.05). IFS- induced microscopic alterations were also prevented by ketamine with or without mesna (P < 0.05). In addition, also statistically insignificant, the bladder tissue expressions of IL-1β were lower in ketamine and/or mesna-receiving groups (P > 0,05). The parameters of oxidative stress, the NO and the MDA contents of the bladder tissues of the study groups were not different.
  
  
  CONCLUSIONS
  The results of the present study suggest that a single dose of ketamine pretreatment attenuates experimental IFS-induced bladder damage. It is therefore necessary to investigate ketamine locally and systematically with various dosing schedules in order to reduce the bladder damage secondary to oxazaphosphorine-alkylating agents and these results may widen the spectrum of ketamine.
authors.affiliation: Department of Pediatric Oncology, Celal Bayar University, School of Medicine, Manisa, Turkey.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Ozguven
authors.affiliation: Department of Pediatric Surgery, Celal Bayar University, School of Medicine, Manisa, Turkey.
authors.forename: Omer
authors.initials: O
authors.lastname: Yılmaz
authors.affiliation: Department of Biochemistry, Celal Bayar University, School of Medicine, Manisa, Turkey.
authors.forename: Fatma
authors.initials: F
authors.lastname: Taneli
authors.affiliation: Department of Biochemistry, Celal Bayar University, School of Medicine, Manisa, Turkey.
authors.forename: Cevval
authors.initials: C
authors.lastname: Ulman
authors.affiliation: Department of Histology and Embriology, Celal Bayar University, School of Medicine, Manisa, Turkey.
authors.forename: Seda
authors.initials: S
authors.lastname: Vatansever
authors.affiliation: Department of Pediatrics, Celal Bayar University, School of Medicine, Manisa, Turkey.
authors.forename: Ali
authors.initials: A
authors.lastname: Onag
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D015415:Biomarkers / Q000032:analysis; D003556:Cystitis / Q000139:chemically induced / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000517:prevention & control*; D007069:Ifosfamide / Q000633:toxicity*; D007150:Immunohistochemistry; D007649:Ketamine / Q000008:administration & dosage / Q000627:therapeutic use*; D015080:Mesna / Q000008:administration & dosage / Q000627:therapeutic use*; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D018906:Antineoplastic Agents, Alkylating; D015415:Biomarkers; D007649:Ketamine; D015080:Mesna; D007069:Ifosfamide
keywords: Hemorrhagic cystitis; Ifosfamide; ketamine; mesna; protective
references.citation: Int J Urol. 2003 Nov;10(11):595-602
references.pmid: 14633084
references.citation: Br J Anaesth. 2005 Dec;95(6):803-10
references.pmid: 16227338
references.citation: Int Braz J Urol. 2007 Sep-Oct;33(5):704-10
references.pmid: 17980069
references.citation: Oxid Med Cell Longev. 2009 Sep-Oct;2(4):207-13
references.pmid: 20716906
references.citation: Cancer Chemother Pharmacol. 2007 Jan;59(1):71-7
references.pmid: 16708234
references.citation: J Pineal Res. 2005 May;38(4):272-7
references.pmid: 15813904
references.citation: Free Radic Biol Med. 1995 Dec;19(6):893-6
references.pmid: 8582665
references.citation: Anesth Analg. 1998 Aug;87(2):266-71
references.pmid: 9706914
references.citation: J Urol. 1986 Aug;136(2):497-500
references.pmid: 3090278
references.citation: J Inflamm (Lond). 2007 May 04;4:10
references.pmid: 17480224
references.citation: Eur J Anaesthesiol. 2005 Sep;22(9):712-6
references.pmid: 16163919
references.citation: Am J Pathol. 1997 Jan;150(1):247-56
references.pmid: 9006340
references.citation: Anesth Analg. 1999 Sep;89(3):665-9
references.pmid: 10475301
references.citation: Clin Chem. 1990 Aug;36(8 Pt 1):1440-3
references.pmid: 2387039
references.citation: J Urol. 1998 Mar;159(3):1044
references.pmid: 9474228
references.citation: Microsc Res Tech. 2011 Dec;74(12):1192-8
references.pmid: 21563274
references.citation: Cell Biol Toxicol. 2007 Sep;23(5):303-12
references.pmid: 17225077
references.citation: Br J Haematol. 1971 Jan;20(1):95-111
references.pmid: 5540044
references.citation: Resuscitation. 2004 Aug;62(2):237-42
references.pmid: 15294410
references.citation: Med Pediatr Oncol. 2003 Sep;41(3):190-7
references.pmid: 12868118
references.citation: Addiction. 2012 Jan;107(1):27-38
references.pmid: 21777321
references.citation: Arch Toxicol. 2005 Aug;79(8):461-5
references.pmid: 15800758
references.citation: Br J Anaesth. 2011 Aug;107(2):123-6
references.pmid: 21757548