Inhibition of cyclooxygenase-2 aggravates doxorubicin-mediated cardiac injury in vivo

Q: What is the clinical evidence from this study?

Population: Doxorubicin-induced cardiac injury. Intervention: SC236 (COX-2 inhibitor) with Doxorubicin vs. Doxorubicin alone. Primary outcome: Plasma lactate dehydrogenase (LDH) level at 4 hours (p=0.02).

N. Dowd; Michael Scully; Sharon R. Adderley; Anthony J. Cunningham; Desmond J. Fitzgerald

doi:10.1172/jci200111334

August 15, 2001Journal of Clinical InvestigationOpen Access

Inhibition of cyclooxygenase-2 aggravates doxorubicin-mediated cardiac injury in vivo

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Why the study?

Does inhibition of COX-2 aggravate doxorubicin-mediated cardiac injury in vivo?

Structured PICO

Does inhibition of COX-2 aggravate doxorubicin-mediated cardiac injury in vivo?

P

Population

Male Sprague Dawley rats (6-8 weeks old) treated with doxorubicin to induce cardiac injury, evaluated over 4 to 24 hours.

I

Intervention

Doxorubicin (15 mg/kg intraperitoneal) coadministered with selective COX-2 inhibitor SC236 (3 mg/kg x2), selective COX-1 inhibitor SC560 (3-10 mg/kg x2), nonselective inhibitor indomethacin (2 mg/kg x2), or prostacyclin analogue iloprost (9 µg/kg in three divided doses)

C

Comparator

Vehicle (DMSO or saline) control, or doxorubicin alone

O

Outcome

Cardiac injury detected as a rise in plasma cardiac troponin T (CTnT), serum lactate dehydrogenase (LDH), and cardiomyocyte apoptosis (TUNEL assay) at 4 hourssurrogate

Main Result

Absolute Event Rate: 1552% vs 578%

p-value: p=0.02

Limitations

Animal model
Absence of dose-response data for iloprost
Additional mechanisms of cell death induced by DX may not be reversed by iloprost
Cannot exclude additional mechanisms of cell death induced by doxorubicin that are not reversed by iloprost
Cannot exclude the possibility that a vasodilator response to iloprost provided some degree of protection

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Implication

Inhibition of COX-2 aggravates doxorubicin-induced cardiotoxicity in vivo, suggesting that COX-2 induction is a compensatory protective mechanism mediated by prostacyclin.

Abstract

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Cite This Study

Dowd et al. (2001) studied Doxorubicin-induced cardiac injury. SC236 (COX-2 inhibitor) with Doxorubicin vs. Doxorubicin alone was evaluated on Plasma lactate dehydrogenase (LDH) level at 4 hours (p=0.02).

synapsesocial.com/papers/6a22b8489433475d0a11cc6c https://doi.org/10.1172/jci200111334

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Inhibition of cyclooxygenase-2 aggravates doxorubicin-mediated cardiac injury in vivo

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Inhibition of cyclooxygenase-2 aggravates doxorubicin-mediated cardiac injury in vivo

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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