stilbenes and diphenyleneiodonium

NADPH oxidases (NOXs) are a group of enzymes for superoxide anion (O

Topics: Acetophenones; Animals; Humans; Hypertension, Pulmonary; NADPH Oxidases; Onium Compounds; Resveratrol; Stilbenes

Both resveratrol(Res) and diphenyleneiodonium(DPI) have been shown to have radioprotective effects on hematopoietic system injury. However, the cooperative effect of Res and DPI are unknown. In this study, we explored the radioprotective effect of the combination of Res and DPI both in vitro and in vivo. Our results showed that the combined treatment of Res and DPI was more effective in protecting irradiated BMMNCs in terms of cell viability, colony-forming ability, and reconstitution ability in vitro compared with Res or DPI treatment alone. However, in mice, the combination of Res and DPI had no enhanced protection on 4Gy total body irradiation (TBI)-induced hematopoietic system injury, including TBI-induced myelosuppression, induction of the splenic index, and increases in HSC/HPC numbers and the colony-forming ability of BMCs,compared to Res or DPI alone. An exception was the number of BMCs. These studies illustrated the inconsistency between experiments carried out in vitro and in vivo and suggest an interaction between Res or DPI in vivo.

Topics: Animals; Bone Marrow Cells; Cells, Cultured; Drug Interactions; Drug Therapy, Combination; Hematopoietic System; Humans; Male; Mice; Mice, Inbred C57BL; Onium Compounds; Radiation Injuries, Experimental; Resveratrol; Stilbenes; Whole-Body Irradiation

Resveratrol has shown benefits in reducing ventricular remodeling and arrhythmias.. This study aimed to assess the therapeutic efficacy of resveratrol in reducing atrial fibrillation (AF) in a heart failure (HF) model and to explore the underlying mechanisms.. HF rabbits were created 4 weeks after undergoing coronary ligation. Group 1 (n = 6) was divided into subgroups of (a) normal rabbits, (b) HF sham rabbits, and (c) HF rabbits treated for 1 week with intraperitoneal injections of resveratrol, (d) resveratrol plus wortmannin, or (e) resveratrol plus diphenyleneiodonium chloride (DPI). All rabbits underwent epicardial catheter stimulation. Collagen content, messenger RNA and protein expression in ion channels, and phosphoinositide 3-kinase (PI3K)/AKT/endothelial nitric oxide synthase (eNOS) signaling pathways were studied in left atrial appendage (LAA) preparations. To investigate acute drug effects on left atrial electrophysiology, groups 2 a through 2e (n = 6 per group) were subjected to Langendorff perfusion.. Higher AF inducibility was found in the HF group and groups that were given PI3K and eNOS inhibitors than in the normal and resveratrol-treated groups (P < .001). Histologic analysis of the LAA revealed a decrease in fibrosis in resveratrol-treated groups compared with the HF group (8.95% ± 1.53% vs 26.62% ± 2.19%, P < .001). In real-time polymerase chain reaction analysis, ion channels including Kv1.4, Kv1.5, KvLQT1, Kir2.1, Nav1.5, Cav1.2, NCX, SERCA2a, and phospholamban were upregulated by resveratrol. PI3K, AKT, and eNOS messenger RNA and protein expression were upregulated by resveratrol but were inhibited by the coadministration of wortmannin and DPI.. Resveratrol decreases left atrial fibrosis and regulates variation in ion channels to reduce AF through the PI3K/AKT/eNOS signaling pathway.

Topics: Androstadienes; Animals; Antioxidants; Atrial Fibrillation; Disease Models, Animal; Enzyme Activation; Enzyme Inhibitors; Nitric Oxide Synthase Type III; Onium Compounds; Phosphatidylinositol 3-Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt; Rabbits; Resveratrol; Signal Transduction; Stilbenes; Wine; Wortmannin

Glycated serum albumin (GSA) promotes vascular complications in diabetes. The aim of this study was to determine if GSA induces chemokine, particularly CXCL8 (IL-8), and to determine intracellular signaling pathways activated by GSA in vascular smooth muscle cells (VSMCs). GSA increased IL-8 transcription via promoter activation and enhanced CXCL8 release from VSMCs. GSA-induced promoter activation of the IL-8 gene was suppressed by dominant-negative mutants of TLR-4, MyD88, and TRIF, but not by a dominant-negative form of TLR-2. In addition, IL-8 up-regulation in response to GSA was inhibited by resveratrol, curcumin, diphenyleneiodium, U0126, and SB202190. Mutation at the NF-kappaB- or C/EBP-binding site, but not at the AP-1-binding site, in the IL-8 promoter region suppressed GSA-induced promoter activation. Moreover, gene delivery of IkappaB suppressed CXCL8 release. This study suggests that GSA induces expression of IL-8 in VSMCs and that TLR-4, mitogen-activated protein kinases, NF-kappaB, and NADPH oxidase are involved in that process.

Topics: Butadienes; Cells, Cultured; Curcumin; Glycated Serum Albumin; Glycation End Products, Advanced; Humans; Interleukin-8; Mitogen-Activated Protein Kinase Kinases; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; NADPH Oxidases; NF-kappa B; Nitriles; Onium Compounds; Promoter Regions, Genetic; Resveratrol; Serum Albumin; Stilbenes; Toll-Like Receptor 4; Transcriptional Activation; Up-Regulation