title: Tranilast alleviates endothelial dysfunctions and insulin resistance via preserving glutathione peroxidase 1 in rats fed a high-fat emulsion.
abstract: We investigated the effects of treatment with tranilast on vascular and metabolic dysfunction induced by a high-fat emulsion intragastric administration. Wistar rats were randomized to receive water or high-fat emulsion with or without tranilast treatment (400 mg/kg per day) for 4 weeks. Insulin sensitivity was determined with a hyperinsulinemic-euglycemic clamp experiment and short insulin tolerance test. Vascular reactivity was evaluated using aortic rings in organ chambers. Glutathione peroxidase 1 (GPX1) expressions, eNOS phosphorylation and activity, MCP-1, H2O2 formation, and NO production were determined in vascular or soleus tissues. Tranilast treatment was found to prevent alterations in vascular reactivity and insulin sensitivity and to prevent increases in plasma glucose and insulin noted in the high-fat emulsion-treated rats. These were associated with increased antioxidant enzyme GPX1 expression, eNOS phosphorylation and activity, and NO production, but reductions in H2O2 accumulation. Moreover, tranilast preserved GPX1 expression in palmitic acid (PA)-treated endothelial cells with a consequent decreased ROS formation and increased eNOS phosphorylation and NO production. Therefore, oxidative stress induced by a relatively short-term high-fat diet could cause the early development of vascular and metabolic abnormalities in rats, and tranilast has a beneficial effect in vascular dysfunctions and insulin resistance via preserving GPX1 and alleviating oxidative stress.
authors.affiliation: Department of Cardiology, Qingdao Municipal Hospital, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.forename: Changjiang
authors.initials: C
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018932:Chemokine CCL2 / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology*; D005979:Glutathione Peroxidase / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010545:Peroxides / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D062367:ortho-Aminobenzoates / Q000494:pharmacology*; D000094765:Glutathione Peroxidase GPX1
chemical_list: D018926:Anti-Allergic Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D010545:Peroxides; D017382:Reactive Oxygen Species; D062367:ortho-Aminobenzoates; D009569:Nitric Oxide; D005979:Glutathione Peroxidase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C012293:tranilast; D000094765:Glutathione Peroxidase GPX1; C000722069:Gpx1 protein, rat