The role of curcumin as an inhibitor of oxidative stress caused by ischaemia re-perfusion injury in tetralogy of Fallot patients undergoing corrective surgery.
BACKGROUND
Cardiopulmonary bypass during tetralogy of Fallot corrective surgery is associated with oxidative stress, and contributes to peri-operative problems. Curcumin has been known as a potent scavenger of reactive oxygen species, which enhances the activity of antioxidants and suppresses phosphorylation of transcription factors involved in inflamation and apoptosis.


OBJECTIVE
To evaluate the effects of curcumin as an antioxidant by evaluating the concentrations of malondialdehyde and glutathione, activity of nuclear factor-kappa B, c-Jun N-terminal kinase, caspase-3, and post-operative clinical outcomes.


METHODS
Tetralogy of Fallot patients for corrective surgery were randomised to receive curcumin (45 mg/day) or placebo orally for 14 days before surgery. Malondialdehyde and glutathione concentrations were evaluated during the pre-ischaemia, ischaemia, re-perfusion phases, and 6 hours after aortic clamping-off. Nuclear factor-kappa B, c-Jun N-terminal kinase, and caspase-3, taken from the infundibulum, were assessed during the pre-ischaemia, ischaemia, and re-perfusion phases. Haemodynamic parameters were monitored until day 5 after surgery.


RESULTS
In all the observation phases, malondialdehyde and glutathione concentrations were similar between groups. There was no significant difference in nuclear factor-kappa B activity between the groups for three observations; however, in the curcumin group, c-Jun N-terminal kinase significantly decreased from the pre-ischaemia to the re-perfusion phases, and caspase-3 expression was lower in the ischaemia phase. Patients in the curcumin group had lower temperature and better ventricular functions, but no significant differences were found in mechanical ventilation day or length of hospital stay in the two groups.


CONCLUSIONS
Cardioprotective effects of curcumin may include inhibition of the c-Jun N-terminal kinase pathway and caspase-3 in cardiomyocytes, particularly in the ischaemia phase.
1Integrated Cardiovascular Service,Dr Cipto Mangunkusumo General Hospital,Jakarta,Indonesia.
Rubiana
R
Sukardi
2Department of Child Health,Cardiology Division, Medical Faculty,University of Indonesia,Jakarta,Indonesia.
Sudigdo
S
Sastroasmoro
3Department of Pathology Anatomy, Medical Faculty,University of Indonesia,Jakarta,Indonesia.
Nurjati C
NC
Siregar
2Department of Child Health,Cardiology Division, Medical Faculty,University of Indonesia,Jakarta,Indonesia.
Mulyadi M
MM
Djer
4Department of Pharmacology, Medical Faculty,University of Indonesia,Jakarta,Indonesia.
Fransciscus D
FD
Suyatna
5Department of Biochemistry, Medical Faculty,University of Indonesia,Jakarta,Indonesia.
Mohammad
M
Sadikin
6Department of Physiology, Medical Faculty,University of Indonesia,Jakarta,Indonesia.
Nurhadi
N
Ibrahim
7Department of Child Health,Cardiology Division, Medical Faculty,University of Padjajaran,Bandung,Indonesia.
Sri E
SE
Rahayuningsih
8Research and Development Laboratory,Dharmais Hospital National Cancer Center,Jakarta,Indonesia.
Arief B
AB
Witarto
D000975:Antioxidants / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D053148:Caspase 3 / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003474:Curcumin / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics; D006801:Humans; D007214:Indonesia; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D032383:Myocytes, Cardiac / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D015427:Reperfusion Injury / Q000188:drug therapy*; D013771:Tetralogy of Fallot / Q000628:therapy*
D000975:Antioxidants; D048031:JNK Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D003474:Curcumin
Curcumin; apoptosis; ischaemia re-perfusion injury