title: Aminoguanidine pretreatment prevents methotrexate-induced small intestinal injury in the rat by attenuating nitrosative stress and restoring the activities of vital mitochondrial enzymes.
abstract: BACKGROUND
  One of the major toxic side effects of methotrexate (MTX) is enterocolitis, for which there is no efficient standard treatment. Nitric oxide overproduction has been reported to play an important role in MTX-induced mucositis. This study was designed to investigate whether pretreatment with aminoguanidine (AG) - a selective iNOS inhibitor - prevents MTX-induced mucositis in rats.
  
  
  METHODS
  Rats were pretreated with AG (30 and 50 mg/kg body weight) i.p. daily 1 h before MTX (7 mg/kg body weight) administration for 3 consecutive days. After the final dose of MTX, the rats were killed, and the small intestines were used for analysis.
  
  
  RESULTS
  The small intestines of MTX-treated rats showed moderate to severe injury. Pretreatment with AG had a dose-dependent protective effect on MTX-induced mucositis. AG pretreatment reduced iNOS protein levels, mucosal nitric oxide levels, and protein tyrosine nitration. AG pretreatment also restored the activities of electron transport chain (ETC) complexes, vital tricarboxylic acid (TCA cycle) enzymes, and mitochondrial antioxidant enzymes.
  
  
  CONCLUSIONS
  These findings suggest that AG is beneficial in ameliorating MTX-induced enteritis in rats.
authors.affiliation: Department of Biochemistry, Christian Medical College, Bagayam, Vellore, Tamil Nadu.
authors.forename: Kasthuri
authors.initials: K
authors.lastname: Natarajan
authors.affiliation: Department of Biochemistry, Christian Medical College, Bagayam, Vellore 632002, Tamil Nadu.
authors.forename: Premila
authors.initials: P
authors.lastname: Abraham
authors.affiliation: Department of Pathology, Madha Medical College, Thandalam, Kovur, Chennai, Tamil Nadu.
authors.forename: Rekha
authors.initials: R
authors.lastname: Kota
authors.affiliation: Department of Biochemistry, Christian Medical College, Bagayam, Vellore, Tamil Nadu.
authors.forename: Dhayakani
authors.initials: D
authors.lastname: Selvakumar
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002952:Citric Acid Cycle / Q000187:drug effects; D004579:Electron Transport / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology*; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D000073039:Nitrosative Stress / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D006146:Guanidines; D009569:Nitric Oxide; C004479:pimagedine; D008727:Methotrexate
keywords: ETC activity; TCA cycle enzymes; aminoguanidine; antioxidant enzymes; methotrexate; nitrosative stress; small intestinal injury