TY - JOUR
T1 - Carvedilol attenuates inflammatory-mediated cardiotoxicity in daunorubicin-induced rats
AU - Sari, Flori R.
AU - Arozal, Wawaimuli
AU - Watanabe, Kenichi
AU - Harima, Meilei
AU - Veeravedu, Punniyakoti T.
AU - Thandavarayan, Rajarajan A.
AU - Suzuki, Kenji
AU - Arumugam, Somasundaram
AU - Soetikno, Vivian
AU - Kodama, Makoto
PY - 2011
Y1 - 2011
N2 - Cardiotoxicity, which results from intense cardiac oxidative stress and inflammation, is the main limiting factor of the anthracyclines. Carvedilol, a beta blocker that is used as a multifunctional neurohormonal antagonist, has been shown to act not only as an anti-oxidant, but also as an anti-inflammatory drug. This study was designed to evaluate whether carvedilol exerts a protective role against inflammation-mediated cardiotoxicity in the daunorubicin (DNR)-induced rats. Carvedilol was administered orally to the rats every day for 6 weeks at a cumulative dose of 9 mg/kg body weight DNR. DNR significantly induced cardiac damage and worsened cardiac function as well as increased cardiac mast cell density, elevating the myocardial protein and mRNA expression levels of tumor necrosis factor-α, vascular cell adhesion molecule-1, inter-cellular adhesion molecule-1, nuclear factor kappa-B, cyclooxygenase-2, monocyte chemotactic protein -1 and interleukin -6 compared to that in the control group. Cotreatment with carvedilol significantly attenuated the myocardial protein and mRNA expression levels of these inflammatory markers, decreased cardiac mast cell density, improved histological cardiac damage and cardiac functions. In conclusion, inflammation plays a significant role in DNR-induced cardiotoxicity, and carvedilol contributes to cardioprotection against inflammation-mediated cardiotoxicity in DNR-induced rats through its anti-inflammatory mechanism.
AB - Cardiotoxicity, which results from intense cardiac oxidative stress and inflammation, is the main limiting factor of the anthracyclines. Carvedilol, a beta blocker that is used as a multifunctional neurohormonal antagonist, has been shown to act not only as an anti-oxidant, but also as an anti-inflammatory drug. This study was designed to evaluate whether carvedilol exerts a protective role against inflammation-mediated cardiotoxicity in the daunorubicin (DNR)-induced rats. Carvedilol was administered orally to the rats every day for 6 weeks at a cumulative dose of 9 mg/kg body weight DNR. DNR significantly induced cardiac damage and worsened cardiac function as well as increased cardiac mast cell density, elevating the myocardial protein and mRNA expression levels of tumor necrosis factor-α, vascular cell adhesion molecule-1, inter-cellular adhesion molecule-1, nuclear factor kappa-B, cyclooxygenase-2, monocyte chemotactic protein -1 and interleukin -6 compared to that in the control group. Cotreatment with carvedilol significantly attenuated the myocardial protein and mRNA expression levels of these inflammatory markers, decreased cardiac mast cell density, improved histological cardiac damage and cardiac functions. In conclusion, inflammation plays a significant role in DNR-induced cardiotoxicity, and carvedilol contributes to cardioprotection against inflammation-mediated cardiotoxicity in DNR-induced rats through its anti-inflammatory mechanism.
KW - Carvedilol
KW - Daunorubicin
KW - Fibrosis
KW - Inflammation
UR - http://www.scopus.com/inward/record.url?scp=79955586122&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79955586122&partnerID=8YFLogxK
U2 - 10.3390/ph4030551
DO - 10.3390/ph4030551
M3 - Article
AN - SCOPUS:79955586122
SN - 1424-8247
VL - 4
SP - 551
EP - 566
JO - Pharmaceuticals
JF - Pharmaceuticals
IS - 3
ER -