title: Multi-drug resistance protein (Mrp) 3 may be involved in resveratrol protection against methotrexate-induced testicular damage.
abstract: OBJECTIVE
  To investigate the effect of resveratrol (RES) on methotrexate (MTX)-induced testicular damage.
  
  
  METHODS
  RES (10mg/kg/day) was given for 8 days orally and MTX (20mg/kg i.p.) was given at day 4 of the experiment, with or without RES in rat.
  
  
  RESULTS
  MTX decreased serum testosterone, induced histopathological testicular damage, and increased testicular tumor necrosis factor-α level and expression of nuclear factor-κB and cyclooxygenase-2. In MTX/RES group, significant reversal of these parameters was noticed, compared to MTX group. Testicular expression of multidrug resistance protein (Mrp) 3 was three- and five-folds higher in RES- and MTX/RES-treated groups, respectively. In vitro, using prostate cancer cells, each of MTX and RES alone induced cytotoxicity with IC50 0.18 ± 0.08 and 20.5 ± 3.6 μM, respectively. RES also significantly enhanced cytotoxicity of MTX.
  
  
  CONCLUSIONS
  Thus, RES has dual beneficial effects, as it promotes MTX tumor cytotoxicity, while protecting the testes, probably via up-regulation of testicular Mrp3 as a novel mechanism.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, Egypt.
authors.forename: Azza A K
authors.initials: AA
authors.lastname: El-Sheikh
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, Egypt; Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia. Electronic address: momorsy@kfu.edu.sa.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Morsy
authors.affiliation: Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, King Faisal University, Al-Ahsa, Saudi Arabia.
authors.forename: Abdulla Y
authors.initials: AY
authors.lastname: Al-Taher
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D000975:Antioxidants / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000032:analysis / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013737:Testis / Q000187:drug effects* / Q000473:pathology*; D013739:Testosterone / Q000097:blood
chemical_list: D000964:Antimetabolites, Antineoplastic; D000975:Antioxidants; D008727:Methotrexate; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D020011:Protective Agents; D000077185:Resveratrol; D013267:Stilbenes; D013739:Testosterone; C114462:multidrug resistance-associated protein 3
keywords: Cyclooxygenase-2; Methotrexate; Multidrug resistance protein 3; Nuclear factor-κB; Resveratrol; Tumor necrosis factor-α