Inhibition of NFkappaB activation with curcumin attenuates plasma inflammatory cytokines surge and cardiomyocytic apoptosis following cardiac ischemia/reperfusion.
BACKGROUND
Following cardiopulmonary bypass (CPB) and cardiac global ischemia and reperfusion, pro-inflammatory cytokines are activated and cause cardiomyocytic injury. Nuclear factor (NF)-kappaB is involved in regulating inflammatory signal transduction. Curcumin inhibits NF-kappaB activation and blocks the inflammatory responses. We studied whether curcumin could decrease myocardial ischemia/reperfusion injury with cardioplegia during CPB and attenuate the appearance of apoptosis of cardiomyocytes.


METHODS
Rabbits received normal saline (group 1) or curcumin (70 mum/kg, group 2; 100 mum/kg, group 3) injection 2 h before CPB. Total CPB was initiated and cold (4 degrees C) antegrade intermittent crystalloid cardioplegia was delivered every 20 min for 60 min of cardiac arrest. Rabbits were weaned from CPB and reperfused for 4 h. Blood was sampled at various time points and then the reperfused hearts were harvested.


RESULTS
Postoperative elevation of plasma levels of interleukin (IL)-8 (14.5, 0.9, 2.9 times over baseline in groups 1-3, respectively, P < 0.05), IL-10 (201.1, 6.0, 14.9 times over baseline in groups 1-3, respectively, P < 0.05), TNF-alpha (9.4, 3.1, 3.9 times over baseline in groups 1-3, respectively, P < 0.05), and cardiac troponin I (141.2, 14.9, 15.0 times over baseline) significantly decreased in the curcumin groups. Appearance of apoptotic cardiomyocytes significantly decreased in the curcumin groups (5.69 +/- 1.64, 1.51 +/- 0.41, 2.43 +/- 0.49 per 1000 nuclei in groups 1-3, respectively, P < 0.01). The activation of neutrophil in the myocardium, which was measured using myocardial myloperoxidase activity assay, was significantly attenuated in the curcumin group. There was a significant increase in apoptosis-related cleavage fragments of caspase-3 and poly-ADP-ribose polymerase in group 1 compared to the other groups.


CONCLUSIONS
Curcumin, an inhibitor of NF-kappaB, ameliorated the surge of pro-inflammatory cytokines during CPB and decreased the occurrence of cardiomyocytic apoptosis after global cardiac ischemia/reperfusion injury.
Yeh
Chi-Hsiao
CH
Division of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Keelung, Taiwan. yehccl@cgmh.org.tw
Chen
Tzu-Ping
TP
Wu
Yi-Cheng
YC
Lin
Yu-Min
YM
Jing Lin
Pyng
P
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002315:Cardiopulmonary Bypass; D003474:Curcumin / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D021381:Protein Transport / Q000187:drug effects; D011817:Rabbits
D016207:Cytokines; D016328:NF-kappa B; D003474:Curcumin