Lead promotes hydroxyl radical generation and lipid peroxidation in cultured aortic endothelial cells.
Early studies by our group have shown that lead-induced hypertension (HTN) is closely related to enhanced activity of reactive oxygen species (ROS). In addition, we have found indirect evidence that hydroxyl radical may be the most likely culprit in lead-exposed animals. In the present study, rat aortic endothelial cells were incubated in the presence of 0, 0.01, 0.1, 0.5, and 1.0 ppm lead acetate for 1, 24, and 48 h. At the conclusion of the incubation period cells were harvested and the media were collected. Lipid peroxidation products were measured as malondialdehyde-thiobarbituric acid (MDA-TBA) in the medium and hydroxyl radical was measured as 2,3-dihydroxybenzoic acid (2,3 DHBA) in the cells. After exposure to lead for 48 h, MDA-TBA generation and 2,3 DHBA formation were significantly increased. These data clearly demonstrate that lead exposure promotes hydroxyl radical generation and induces oxidative stress in isolated endothelial cells, mimicking the effects observed in lead-exposed animals. Enhanced inactivation of endothelium-derived nitric oxide by locally produced oxygen free radicals could contribute to endothelial dysfunction and HTN in lead-exposed animals.
Ding
Y
Y
Department of Medicine, University of California, Irvine, USA.
Gonick
H C
HC
Vaziri
N D
ND
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007854:Lead / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013858:Thiobarbiturates / Q000378:metabolism
D003470:Culture Media; D062385:Hydroxybenzoates; D013858:Thiobarbiturates; D007854:Lead; D017665:Hydroxyl Radical; D008315:Malondialdehyde; C009135:2,3-dihydroxybenzoic acid; C029684:thiobarbituric acid