Are the antioxidant properties of carvedilol important for the protection of cardiac mitochondria?
The cellular role of mitochondria includes ATP generation and the modulation of cytosolic calcium signals, besides being the "crossroads" for several cell death pathways. The maintenance of optimal mitochondrial functioning during the disease process increases the chances for survival. For example, ischaemia followed by reperfusion is known to negatively affect mitochondrial function, namely by inducing a deleterious condition called mitochondrial permeability transition (MPT). The MPT is responsible for mitochondrial dysfunction and can ultimately lead to cell death. Therefore, it seems important to protect mitochondrial function in cardiac disease. Carvedilol, a beta-adrenergic receptor antagonist with antioxidant properties, has a positive impact on cardiac mitochondria during in vitro, ex-vivo and in vivo models of cardiac dysfunction. Particularly, carvedilol was shown to inhibit MPT in isolated heart mitochondria and protect mitochondria against the oxidative damage induced by the xanthine oxidase/hypoxanthine pro-oxidant system. The observation that carvedilol acts as an inhibitor of mitochondrial complex-I is also of importance, since this mitochondrial system was proposed as cause of the cardiotoxicity associated with the anti-neoplasic drug doxorubicin. This review points out the major findings concerning the positive impact of carvedilol on mitochondrial function and its use in the treatment of myocardial diseases where oxidative stress is known to be involved.
Oliveira
Paulo J
PJ
Center for Neurosciences and Cellular Biology of Coimbra, University of Coimbra, P-3000-075 Coimbra, Portugal.
Gonçalves
Lino
L
Monteiro
Pedro
P
Providencia
Luis A
LA
Moreno
Antonio J
AJ
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology*; D009202:Cardiomyopathies / Q000139:chemically induced / Q000517:prevention & control; D000077261:Carvedilol; D006801:Humans; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control; D010539:Permeability; D011412:Propanolamines / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D000975:Antioxidants; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol