Inhibition of NFκB activation with curcumin attenuates plasma inflammatory cytokines surge and cardiomyocytic apoptosis following cardiac ischemia/reperfusion

Chi Hsiao Yeh*, Tzu Ping Chen, Yi Cheng Wu, Yu Min Lin, Pyng Jing Lin

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

122 Scopus citations

Abstract

Background. Following cardiopulmonary bypass (CPB) and cardiac global ischemia and reperfusion, pro-inflammatory cytokines are activated and cause cardiomyocytic injury. Nuclear factor (NF)-κB is involved in regulating inflammatory signal transduction. Curcumin inhibits NF-κB 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. Materials and methods. Rabbits received normal saline (group 1) or curcumin (70 μm/kg, group 2; 100 μm/kg, group 3) injection 2 h before CPB. Total CPB was initiated and cold (4°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-α (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-κB, ameliorated the surge of pro-inflammatory cytokines during CPB and decreased the occurrence of cardiomyocytic apoptosis after global cardiac ischemia/reperfusion injury.

Original languageEnglish
Pages (from-to)109-116
Number of pages8
JournalJournal of Surgical Research
Volume125
Issue number1
DOIs
StatePublished - 01 05 2005
Externally publishedYes

Keywords

  • Apoptosis
  • Cardiopulmonary bypass
  • Curcumin
  • NFκB

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