Effect of selective and non-selective cyclooxygenase inhibitors on doxorubicin-induced cardiotoxicity and nephrotoxicity in rats

Mohamed A. Ibrahim, Mohamed A. Morsy, Heba M. Hafez, Wafaey M. Gomaa, Aly M. Abdelrahman

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Context: 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. Materials and 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. Discussion and conclusion: 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).

Original languageEnglish
Pages (from-to)424-431
Number of pages8
JournalToxicology Mechanisms and Methods
Volume22
Issue number6
DOIs
Publication statusPublished - Jul 2012

Fingerprint

Cyclooxygenase Inhibitors
Doxorubicin
Rats
nimesulide
Cyclooxygenase 2
Indomethacin
Cyclooxygenase 2 Inhibitors
Celecoxib
Tissue
Cardiotoxicity
Diclofenac
Wounds and Injuries
Wistar Rats
Tumors

Keywords

  • Indomethacin
  • malondialdehyde
  • nimesulide
  • reduced glutathione

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Effect of selective and non-selective cyclooxygenase inhibitors on doxorubicin-induced cardiotoxicity and nephrotoxicity in rats. / Ibrahim, Mohamed A.; Morsy, Mohamed A.; Hafez, Heba M.; Gomaa, Wafaey M.; Abdelrahman, Aly M.

In: Toxicology Mechanisms and Methods, Vol. 22, No. 6, 07.2012, p. 424-431.

Research output: Contribution to journalArticle

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AB - Context: 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. Materials and 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. Discussion and conclusion: 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).

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