Cilostazol does not improve peripheral arterial disease-linked oxidative stress.
OBJECTIVE
Cilostazol is a drug widely used to treat peripheral arterial disease (PAD) in patients with advanced atherosclerosis. It is an inhibitor of platelet aggregation and causes arterial vasodilatation. It has been speculated that cilostazol might act to improve oxidative stress in these patients.


METHODS
We analyzed 25 patients with demonstrated lower limb peripheral arterial disease to determine whether lipid peroxidation (LPO) or total antioxidant capacity (TAC) were modified after 6 months of cilostazol treatment (postintervention phase) with respect to the basal phase.


RESULTS
Analysis of plasma samples determined that LPO levels decreased significantly over the postintervention phase (26±15 vs. 11±7 pM, P=0.0003). However, when TAC levels were analyzed, no significant differences were observed (0.80±0.21 vs. 0.85±0.17 mM, P=0.42). Under basal conditions, LPO showed a positive correlation to treatment as judged by the ankle-brachial index (r=0.800, P=0.002) as well as uric acid (r=0.508, P=0.03) and CRP (r=0.481, P=0.05) levels. In contrast, TAC negatively correlated with triglycerides (r=-0.879, P<0.0001) and microalbuminuria (r=-0.868, P<0.0001). In the postintervention phase, TAC negatively correlated with HbA1c (r=-0.570, P=0.02) and triglycerides (r=-0.864, P<0.0001).


CONCLUSIONS
Our data indicate that cilostazol treatment does not improve oxidative stress in PAD patients after 6 months of treatment. However, lipid peroxidation and total antioxidant capacity were affected by cilostrazol treatment, which could be related to altered reactive oxygen species production. Further research may be needed to determine the critical dose of cilostazol to clarify the protective role of this drug in PAD.
Biomedical Research Laboratory, Internal Medicine Department, Biomedical Institute of Malaga (IBIMA), University Hospitals, Regional and Clinical Virgen de la Victoria of Malaga, Malaga, Spain; Ciber Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.
M Rosa
MR
Bernal-Lopez
Daniel
D
Peña
Pilar
P
Gomez-Martin
Francisco J
FJ
Tinahones
Ricardo
R
Gomez-Huelgas
D000368:Aged; D000975:Antioxidants / Q000378:metabolism; D000077407:Cilostazol; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D058729:Peripheral Arterial Disease / Q000188:drug therapy / Q000503:physiopathology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use
D000975:Antioxidants; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D000077407:Cilostazol
Oxidative stress; Peripheral arterial disease; Platelet aggregation; Type 2 diabetes mellitus