title: Protective Effects of Infliximab on Lung Injury Induced by Methotrexate.
abstract: BACKGROUND
  Methotrexate (MTX) is used to treat cancers, several forms of arthritis and other rheumatic conditions, although MTX may cause pulmonary toxicity related to the production of free oxygen radicals, various cytokines. Infliximab (IB) with its potent effect on tumor necrosis factor-alpha (TNF-α) inhibition also inhibits the release of endothelin-1 (ET-1). We aimed to investigate whether IB reduces pulmonary damage induced by an overdose of MTX.
  
  
  METHODS
  The rats were divided into 3 groups of 8 animals. The control group was given only saline. One dose of 20mg/kg MTX intraperitoneal was administered in the MTX group. IB 7 mg/kg was given to the MTX+IB (MI) group. Three days after IB was administered, 20mg/kg MTX was given. Five days after MTX was administered, all rats were sacrificed.
  
  
  RESULTS
  The TNF-α, ET-1, malondialdehyde (MDA), myeloperoxidase (MPO) and caspase-3 levels in MTX group were significantly higher than in control groups of TNF-α (P=.001), ET-1 (P=.001), MDA (P=.001), MPO (P=.001) and caspase-3 levels (P=.001) and MI groups of TNF-α (P=.009), ET-1 (P=.001), MDA (P=.047), MPO (P=.007) and caspase-3 levels (P=.003). The MI group had less histopathological damage in lung tissue than the MTX group.
  
  
  CONCLUSIONS
  Overdose of MTX leads to cytokine release and the formation of reactive oxygen species in addition to increased ET-1 secretion release that causes lung damage. IB, as a potent proinflammatory agent, TNF-α blocker, can decrease ET-1 release and oxidative stress, it may show significant protective effects in lung tissue against damage caused by MTX overdose.
authors.affiliation: Department of Thoracic Surgery, School of Medicine, Recep Tayyip Erdogan University, Rize, Turquía. Electronic address: drayselkurt@yahoo.com.
authors.forename: Aysel
authors.initials: A
authors.lastname: Kurt
authors.affiliation: Department of Histology and Embryology, School of Medicine, Recep Tayyip Erdogan University, Rize, Turquía.
authors.forename: Levent
authors.initials: L
authors.lastname: Tumkaya
authors.affiliation: Department of Thoracic Surgery, School of Medicine, Recep Tayyip Erdogan University, Rize, Turquía.
authors.forename: Hasan
authors.initials: H
authors.lastname: Turut
authors.affiliation: Department of Biochemistry, School of Medicine, Recep Tayyip Erdogan University, Rize, Turquía.
authors.forename: Medine Cumhur
authors.initials: MC
authors.lastname: Cure
authors.affiliation: Department of Internal Medicine, School of Medicine, Recep Tayyip Erdogan University, Rize, Turquía.
authors.forename: Erkan
authors.initials: E
authors.lastname: Cure
authors.affiliation: Department of Histology and Embryology, School of Medicine, Recep Tayyip Erdogan University, Rize, Turquía.
authors.forename: Yildiray
authors.initials: Y
authors.lastname: Kalkan
authors.affiliation: Department of Pathology, School of Medicine, RecepTayyip Erdogan University, Rize, Turquía.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Sehitoglu
authors.affiliation: Department of Thoracic Surgery, School of Medicine, Recep Tayyip Erdogan University, Rize, Turquía.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Acipayam
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000032:analysis; D004353:Drug Evaluation, Preclinical; D019332:Endothelin-1 / Q000032:analysis; D000069285:Infliximab / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D008727:Methotrexate / Q000009:adverse effects*; D020556:Neutrophil Infiltration; D009195:Peroxidase / Q000032:analysis; D011650:Pulmonary Alveoli / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000037:antagonists & inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D019332:Endothelin-1; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D000069285:Infliximab; D009195:Peroxidase; C505410:Casp3 protein, rat; D053148:Caspase 3; D008727:Methotrexate
keywords: Endotelina-1; Endothelin-1; Factor de necrosis tumoral-alfa; Infliximab; Methotrexate; Metotrexato; Pulmonary toxicity; Toxicidad pulmonar; Tumor necrosis factor alpha