title: Effect of treatment with the antioxidant alpha-lipoic (thioctic) acid on heart and kidney microvasculature in spontaneously hypertensive rats.
abstract: Endothelial cells represent an important vascular site of signaling and development of damage during ischemia, inflammation and other pathological conditions. Excessive reactive oxygen species production causes pathological activation of endothelium including exposure of cell to adhesion molecules. Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) are members of the immunoglobulin super-family which are present on the surface of endothelial cells. These molecules represent important markers of endothelial inflammation. The present study was designed to investigate, with immunochemical and immunohistochemical techniques, the effect of treatment with (+/-)-alpha lipoic (thioctic) acid and its enantiomers on heart and kidney endothelium in spontaneously hypertensive rats (SHR). Arterial hypertension is accompanied by an increased oxidative stress status in the heart characterized by thiobarbituric acid reactive substances (TBARS) and nucleic acid oxidation increase. The higher oxidative stress also modifies adhesion molecules expression. In the heart VCAM-1, which was higher than ICAM-1 and PECAM-1, was increased in SHR. ICAM-1, VCAM-1 and PECAM-1 expression was significantly greater in the renal endothelium of SHR. (+/-)-Alpha lipoic acid and (+)-alpha lipoic acid treatment significantly decreased TBARS levels, the nucleic acid oxidation and prevented adhesion molecules expression in cardiac and renal vascular endothelium. These data suggest that endothelial molecules may be used for studying the mechanisms of vascular injury on target organs of hypertension. The effects observed after treatment with (+)-alpha lipoic acid could open new perspectives for countering heart and kidney microvascular injury which represent a common feature in hypertensive end-organs damage.
authors.affiliation: a School of Pharmacy, University of Camerino , Camerino , Italy .
authors.forename: Seyed Khosrow
authors.initials: SK
authors.lastname: Tayebati
authors.affiliation: b School of Bioscience and Veterinary Medicine, University of Camerino , Camerino , Italy, and.
authors.forename: Daniele
authors.initials: D
authors.lastname: Tomassoni
authors.affiliation: c Department of Clinical and Preclinical Pharmacology , University of Florence , Florence , Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Di Cesare Mannelli
authors.affiliation: a School of Pharmacy, University of Camerino , Camerino , Italy .
authors.forename: Francesco
authors.initials: F
authors.lastname: Amenta
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1; D007668:Kidney / Q000098:blood supply / Q000378:metabolism; D008297:Male; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017382:Reactive Oxygen Species / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology*; D016896:Treatment Outcome; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D008063:Thioctic Acid
keywords: Alpha-lipoic acid; endothelial adhesion molecules; spontaneously hypertensive rats