Curcumin protects cardiac cells against ischemia-reperfusion injury: effects on oxidative stress, NF-kappaB, and JNK pathways.
In this study we explored the effects of curcumin in cardiac cells subjected to a protocol simulating ischemia-reperfusion (IR). Curcumin (10 microM) was administered before ischemia (pretreatment) or at the moment of reperfusion (posttreatment) and its effects were compared to those produced by a reference antioxidant (Trolox) with an equal antioxidant capacity. IR cardiac cells showed clear signs of oxidative stress, impaired mitochondrial activity, and a marked development of both necrotic and apoptotic processes; at the same time, increases in NF-kappaB nuclear translocation and JNK phosphorylation were observed. Curcumin pretreatment was revealed to be the most effective in attenuating all these modifications and, in particular, in reducing the death of IR cells. This confirms that the protective effect of curcumin is not related simply to its antioxidant properties but involves other mechanisms, notably interactions in the NF-kappaB and JNK pathways. These findings suggest that curcumin administration, in particular before the hypoxic challenge, represents a promising approach to protecting cardiac cells against IR injury. In this scenario our results point out the importance of the chronology for the outcome of the treatment and provide a differential valuation of the degree of protection that curcumin can exert by its antioxidant activity or by other mechanisms.
Fiorillo
Claudia
C
Department of Biochemical Sciences University of Florence, 50134 Florence, Italy. claudia.fiorillo@unifi.it
Becatti
Matteo
M
Pensalfini
Anna
A
Cecchi
Cristina
C
Lanzilao
Luisa
L
Donzelli
Gianpaolo
G
Nassi
Niccolò
N
Giannini
Lara
L
Borchi
Elisabetta
E
Nassi
Paolo
P
D000818:Animals; D015153:Blotting, Western; D016923:Cell Death; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation; D048670:MAP Kinase Kinase 4 / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D021381:Protein Transport; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control*
D016328:NF-kappa B; D017382:Reactive Oxygen Species; D007770:L-Lactate Dehydrogenase; D048670:MAP Kinase Kinase 4; D003474:Curcumin