title: Effects of quercetin on methotrexate-induced nephrotoxicity in rats.
abstract: OBJECTIVE
  This experimental study was conducted to elucidate the possible protective/therapeutic effects of quercetin against methotrexate (Mtx)-induced kidney toxicity with biochemical and histopathological studies.
  
  
  METHODS
  Twenty-four adult male rats were randomly divided into four groups, as follows: control group (saline intraperitoneally (i.p.), 9 days), Mtx group (20 mg/kg i.p., single dose), Mtx + quercetin group (50 mg/kg quercetin was orally administered 2 days before and 6 days after Mtx administration) and only quercetin group (50 mg/kg oral, 9 days). Structural changes were evaluated by hematoxylin-eosin and periodic acid-Schiff stainings. Apoptotic changes were investigated by terminal deoxynucleotidyl transferase dUTP nick end labeling assay and caspase-3 antibody. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured in tissue and plasma samples.
  
  
  RESULTS
  Mtx compared with the control group, there was significant increase in nephrotoxic tissue damage findings, in addition to apoptotic index (APOI) and caspase-3 expression ( p < 0.05). Mtx + quercetin group revealed significantly lower histopathological damage and APOI and caspase-3 expression decreased when compared to Mtx group. MDA levels were increased in Mtx group compared to others, and by the use of quercetin, this increase was significantly reduced. SOD levels were higher in Mtx group than others. This increase was evaluated as a relative increase arising from oxidative damage caused by Mtx.
  
  
  CONCLUSIONS
  As a result, Mtx administration may involve oxidative stress by causing structural and functional damage in kidney tissue in rats. Quercetin reduced the Mtx-induced oxidative stress through its antioxidant properties and so quercetin may be promising to alleviate Mtx-induced renal toxicity.
authors.affiliation: 1 Department of Reproductive Endocrinology and IVF, Laboratory of ART, Dr. Zekai Tahir Burak Women's Health Education and Research Hospital, Ankara, Turkey.
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Yuksel
authors.affiliation: 2 Department of Physiology, Faculty of Medicine, Yildirim Beyazit University, Ankara, Turkey.
authors.forename: Ramazan
authors.initials: R
authors.lastname: Yuksel
authors.affiliation: 3 Department of Histology and Embryology, Faculty of Medicine, Turgut Ozal University, Ankara, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Yagmurca
authors.affiliation: 4 Department of Pathology, Faculty of Medicine, Fatih University, Istanbul, Turkey.
authors.forename: Hacer
authors.initials: H
authors.lastname: Haltas
authors.affiliation: 5 Department of Biochemistry, Faculty of Medicine, Turgut Ozal University, Ankara, Turkey.
authors.forename: Husamettin
authors.initials: H
authors.lastname: Erdamar
authors.affiliation: 6 Department of Anatomy, Faculty of Medicine, Turgut Ozal University, Ankara, Turkey.
authors.forename: Muhsin
authors.initials: M
authors.lastname: Toktas
authors.affiliation: 3 Department of Histology and Embryology, Faculty of Medicine, Turgut Ozal University, Ankara, Turkey.
authors.forename: Osman
authors.initials: O
authors.lastname: Ozcan
keywords: Methotrexate; apoptosis/cell death; oxidative stress; quercetin; renal toxicology