title: Effect of resveratrol on platelet activation in hypercholesterolemic rats: CD40-CD40L system as a potential target.
abstract: Our aim was to investigate whether trans-resveratrol (t-resveratrol), a red wine constituent known for its cardioprotective effects, was able to influence CD40 ligand (CD40L) and its receptor CD40 in platelets of hypercholesterolemic rats. Sixty Wistar rats were divided into 5 groups: control (C), ethanol (E), t-resveratrol (R), hypercholesterolemia (HC), and hypercholesterolemia plus t-resveratrol (HCR). Rats in the C, E, and R groups were fed a normal diet for 80 days. For 20 days before sacrifice, we intraperitoneally (i.p.) administered 0.1 mL ethanol (50% v/v) to the E group, and 0.1 mL t-resveratrol (20 mg·kg(-1)·day(-1)) to the R group. Rats in the HC and HCR groups were fed a 5% cholesterol diet for 80 days. Rats in the HCR group were administered i.p. 0.1 mL t-resveratrol (20 mg·kg(-1)·day(-1)) for 20 days before sacrifice. Serum levels of total cholesterol (TC), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), very low-density lipoprotein (VLDL-C), and total triglycerides (TG) were assayed with a commercial colorimetric kit. Platelet P-selectin, CD40, and CD40L expression was determined by flow cytometry. sCD40L and IL6 levels were measured by ELISA. In the HC group, we observed a significant increase in serum TC, LDL-C, VLDL-C, TG, sCD40, and IL-6 levels and platelet activation markers compared with levels in the control group. However, t-resveratrol administration to the HC group (HCR group) attenuated the increase in lipids, sCD40, and IL-6 and down-regulated platelet P-selectin, CD40, and CD40L expressions. A positive correlation was found for serum lipids and all the platelet activation markers. Our study showed that the CD40-CD40L dyad is up-regulated in the presence of hypercholesterolemia and that t-resveratrol administration down-regulated the increase.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Bozok University, 66200 Yozgat, Turkey.
authors.forename: Ayşe Yeşim
authors.initials: AY
authors.lastname: Göçmen
authors.forename: Durmus
authors.initials: D
authors.lastname: Burgucu
authors.forename: Saadet
authors.initials: S
authors.lastname: Gümüşlü
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism*; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D019013:CD40 Antigens; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D013267:Stilbenes; D023201:CD40 Ligand; D002784:Cholesterol; D000077185:Resveratrol