title: Effect of selective and non-selective cyclooxygenase inhibitors on doxorubicin-induced cardiotoxicity and nephrotoxicity in rats.
abstract: BACKGROUND
  Doxorubicin (DX) is a highly effective chemotherapeutic agent used widely in the treatment of solid tumors; however, its optimal use was associated with cardiotoxicity and nephrotoxicity. The exact mechanism of DX-induced cardiotoxicity and nephrotoxicity is not fully explored. Induction of cyclooxygenase-2 (COX-2) activity in either cardiac or renal tissue by DX has been previously reported, indicating a possible role of COX-2 in DX-induced tissue injury. However, the nature of this role in either tissue injury is an issue of controversy.
  
  
  OBJECTIVE
  This study was the first that simultaneously evaluated the effects of a selective COX-2 inhibitor, nimesulide, and a non-selective COX-inhibitor, indomethacin, on DX-induced cardiotoxicity and nephrotoxicity in male Wistar rats.
  
  
  METHODS
  Rats were allocated into four groups. Control group, DX group (received 15 mg/kg, ip), DX + nimesulide (10 mg/kg/day, po) group, and DX + indomethacin (2 mg/kg/day, po) group. Nimesulide and indomethacin were started at the same day of DX injection and continued for 5 days.
  
  
  RESULTS
  The results of the present study showed that inhibition of COX-2 either by selective or non-selective COX-2 inhibitor ameliorated DX-induced cardiotoxicity but aggravated DX-induced nephrotoxicity in rats, as evidenced biochemically and histopathologically.
  
  
  CONCLUSIONS
  Our study indicates that production of COX-2 is organ specific; consequently, the differential effect of COX-inhibitors should be considered in DX-treated patients. However, a wide scale experiment is needed for further confirmation and testing other members of COX-inhibitors (e.g. celecoxib and diclofenac).
authors.affiliation: Department of Pharmacology, Faculty of Medicine, El-Minia University, El-Minia, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Ibrahim
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Morsy
authors.forename: Heba M
authors.initials: HM
authors.lastname: Hafez
authors.forename: Wafaey M
authors.initials: WM
authors.lastname: Gomaa
authors.forename: Aly M
authors.initials: AM
authors.lastname: Abdelrahman
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004317:Doxorubicin / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D007150:Immunohistochemistry; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D013449:Sulfonamides; D008315:Malondialdehyde; D004317:Doxorubicin; D005978:Glutathione; C012655:nimesulide; D007213:Indomethacin