title: Effect of infliximab on renal injury due to methotrexate in rat.
abstract: BACKGROUND
  Methotrexate, an antagonist of folic acid used in the treatment of many cancers and inflammatory diseases, is associated with side effects that limit its usage. Infliximab has been reported to have a protective effect against nephrotoxicity induced by some drugs and ischemic reperfusion. We aimed to investigate whether infliximab has a protective effect against methotrexate-induced nephrotoxicity.
  
  
  METHODS
  We administered methotrexate at a dose of 20 mg/kg as a single intraperitoneal injection in 10 rats (methotrexate group). Another group of 10 rats received a single dose of infliximab, 7 mg/kg, intraperitoneally (infliximab group). The methotrexate and infliximab group received a similar single injection of infliximab 72 hours prior to methotrexate injection. After 72 hours a single dose of methotrexate, 20 mg/kg, was administered intraperitoneally. Five days after methotrexate injection, blood samples were collected and the kidney tissues were removed for biochemical and histological examination.
  
  
  RESULTS
  The methotrexate group had significantly higher tissue levels of tumor necrosis factor-α (P = .008), interleukin-1β (P = .04), nitric oxide (P < .001), and adenosine deaminase (P < .001) than the methotrexate and infliximab group after the 5-day study. The methotrexate group also had significantly higher total histological scores (P < .001) and carbonic anhydrase-II activity (P < .001) when compared to the methotrexate and infliximab group.
  
  
  CONCLUSIONS
  Infliximab has a strong protective effect against methotrexate-induced nephrotoxicity by suppressing cytokines release. It may decrease methotrexate-induced nephrotoxicity by regulating carbonic anhydrase-II enzyme activities and slowing down purine metabolism.
authors.forename: Aynur
authors.initials: A
authors.lastname: Kirbas
authors.forename: Medine Cumhur
authors.initials: MC
authors.lastname: Cure
authors.forename: Yildiray
authors.initials: Y
authors.lastname: Kalkan
authors.affiliation: Department of Internal Medicine, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey. erkancure@yahoo.com.
authors.forename: Erkan
authors.initials: E
authors.lastname: Cure
authors.forename: Levent
authors.initials: L
authors.lastname: Tumkaya
authors.forename: Osman Zikrullah
authors.initials: OZ
authors.lastname: Sahin
authors.forename: Suleyman
authors.initials: S
authors.lastname: Yuce
authors.forename: Bayram
authors.initials: B
authors.lastname: Kizilkaya
authors.forename: Ahmet
authors.initials: A
authors.lastname: Pergel
mesh_terms: D000243:Adenosine Deaminase / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity; D024402:Carbonic Anhydrase II / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy; D000069285:Infliximab / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000276:immunology* / Q000293:injuries / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000633:toxicity*; D009569:Nitric Oxide / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000964:Antimetabolites, Antineoplastic; D016207:Cytokines; D053583:Interleukin-1beta; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D000069285:Infliximab; D000243:Adenosine Deaminase; D024402:Carbonic Anhydrase II; D008727:Methotrexate