Iloprost attenuates doxorubicin-induced cardiac injury in a murine model without compromising tumour suppression.
OBJECTIVE
The use of doxorubicin (DOX) as a chemotherapeutic agent is limited by cardiac injury. Iloprost, a stable synthetic analogue of prostacyclin, has previously been shown to protect against DOX-induced cardiomyocyte injury in vitro. Here, we addressed whether iloprost is cardioprotective in vivo and whether it compromises the anti-tumour efficacy of DOX.


RESULTS
Lewis Lung Carcinoma cells were implanted subcutaneously in the flank of C57BL/6 mice. DOX treatment was commenced from when tumours became visible. Iloprost was administered from prior to DOX treatment until sacrifice. Echocardiography and invasive haemodynamic measurements were performed immediately before sacrifice. As expected, DOX induced cardiac cell apoptosis and cardiac dysfunction, both of which were attenuated by iloprost. Also, iloprost alone had no effect on tumor growth and indeed, did not alter the DOX-induced suppression of this growth.


CONCLUSIONS
In a murine model, iloprost attenuated the acute cardiac injury and dysfunction induced by DOX therapy without compromising its chemotherapeutic effect.
Neilan
Tomas G
TG
Department of Clinical Pharmacology, Institute of Biopharmaceutical Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland. tneilan@partners.org
Jassal
Davinder S
DS
Scully
Michael F
MF
Chen
Gang
G
Deflandre
Catherine
C
McAllister
Hester
H
Kay
Elaine
E
Austin
Sandra C
SC
Halpern
Elkan F
EF
Harmey
Judy H
JH
Fitzgerald
Desmond J
DJ
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D017209:Apoptosis; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000473:pathology; D009202:Cardiomyopathies / Q000139:chemically induced / Q000517:prevention & control*; D002455:Cell Division; D004317:Doxorubicin / Q000009:adverse effects*; D004347:Drug Interactions; D016285:Iloprost / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000187:drug effects; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D016285:Iloprost