Ediz Demirpece1, Hakan Caner2, Murat Bavbek2
and Kamer Kilinc1
1Hacettepe University, Faculty of Medicine, Department of
Biochemistry, 06100, Ankara, Turkey
2BaSkent University, Faculty of Medicine, Department of Neurosurgery,
06520, Ankara, Turkey
Abstract: Mexiletine is a class Ib antiarrhythmic drug used in
the treatment of ventricular arrhythmias. The Na+ channel blocker
mexiletine inhibits calcium influx in cells via decreasing reverse operation
of the Na+-Ca2+ exchanger. Thus this drug is shown
to protect the CNS white matter against anoxic/ischemic injury. The aim
of our study was to investigate if this drug could act as an antioxidant
drug as well. The antioxidant action of this drug was studied under different
oxidant conditions in vitro, and thiobarbituric acid - reactive substances
were measured to follow lipid peroxidation. Mexiletine inhibited iron-ascorbate-H2O2
- induced lipid peroxidation in brain membranes, liver microsomes and phospholipid
liposomes, being most effective in brain membranes. The inhibition was dose-
and time-dependent. Mexiletine also inhibited copper-ascorbate-H2O2
- induced lipid peroxidation but to a lesser extent. It is concluded that
mexiletine has a dual effect toward oxidative injury in brain, both by inhibiting
Na+-Ca2+ exchanger-dependent Ca2+
influx and by acting as an inhibitor of lipid peroxidation. However, as
this drug is effective at millimolar concentrations, it should be considered
less active than natural antioxidants that are effective at micromolar concentrations.
Keywords: Mexiletine, Antioxidant, Oxidative injury, Lipid peroxidation,
Brain membrane