title: Cilostazol exerts antiplatelet and anti-inflammatory effects through AMPK activation and NF-kB inhibition on hypercholesterolemic rats.
abstract: This work presents a model of rats fed a high-cholesterol diet, receiving a long-term oral administration of cilostazol, a PDE3-inhibitor. The aim of this study was to evaluate the molecular mechanisms by which cilostazol interferes with platelets signaling pathways to avoid atherosclerosis early development. Male Wistar rats were divided into 3 groups: Control group received standard rat chow (C), hypercholesterolemic group (HCD), and HCD+CIL (cilostazol group) received hypercholesterolemic diet for 45 days. HCD+CIL group received cilostazol (30 mg/kg/p.o.) once daily in the last 15 days. Platelet aggregation, lipid profile, lipid peroxidation, and cytokine serum levels were assessed. Expression of P-selectin, CD40L, PKC-α, IkB-α, and iNOS and activation of AMPK, NF-κB, and eNOS in the platelets were assessed using Western blot analysis. Cilostazol reduced the levels of total cholesterol (361.0 ± 12.8 vs. 111.5 ± 1.6 mg/dL), triglycerides (186.9 ± 17.7 vs. 55.4 ±3.1 mg/dL), cLDL (330.9 ± 9.7 vs. 61.5 ± 3.5 mg/dL), cVLDL (45.0 ± 4.6 vs. 11.1 ± 0.6 mg/dL), and malondialdehyde (9.4 ± 0.5 vs. 3.2 ± 0.3 nmol/mL) compared to the HCD group. Cilostazol presented antiplatelet properties and decreased inflammatory markers levels. These effects seem to be related to AMPK activation, NF-kB inhibition, and eNOS activation.
authors.affiliation: Departamento de Fisiologia e Farmacologia, Laboratório de Farmacologia Experimental (LAFE), Instituto Biomédico, Universidade Federal Fluminense (UFF), Sala 204-A, 24230-210, Niterói, Rio de Janeiro, Brazil.
authors.forename: Nadia Alice Vieira
authors.initials: NA
authors.lastname: da Motta
authors.affiliation: Departamento de Fisiologia e Farmacologia, Laboratório de Farmacologia Experimental (LAFE), Instituto Biomédico, Universidade Federal Fluminense (UFF), Sala 204-A, 24230-210, Niterói, Rio de Janeiro, Brazil.
authors.forename: Fernanda Carla Ferreira
authors.initials: FC
authors.lastname: de Brito
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000077407:Cilostazol; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D055372:AMP-Activated Protein Kinases; D000077407:Cilostazol
keywords: AMP-activatedprotein kinase; NF-kB; anti-inflammatory; antiplatelet; atherosclerosis; cilostazol