TY - JOUR
T1 - Effect of selective and non-selective cyclooxygenase inhibitors on doxorubicin-induced cardiotoxicity and nephrotoxicity in rats
AU - Ibrahim, Mohamed A.
AU - Morsy, Mohamed A.
AU - Hafez, Heba M.
AU - Gomaa, Wafaey M.
AU - Abdelrahman, Aly M.
PY - 2012/7
Y1 - 2012/7
N2 - 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).
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).
KW - Indomethacin
KW - malondialdehyde
KW - nimesulide
KW - reduced glutathione
UR - http://www.scopus.com/inward/record.url?scp=84862258469&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862258469&partnerID=8YFLogxK
U2 - 10.3109/15376516.2012.666658
DO - 10.3109/15376516.2012.666658
M3 - Article
C2 - 22394338
AN - SCOPUS:84862258469
SN - 1537-6516
VL - 22
SP - 424
EP - 431
JO - Toxicology Mechanisms and Methods
JF - Toxicology Mechanisms and Methods
IS - 6
ER -