Oxidative stress and apoptotic changes in primary cultures of rat proximal tubular cells exposed to lead.
Lead is a known nephrotoxic element. In this study, primary cultures of rat proximal tubular (rPT) cells were treated with different concentrations of lead acetate (0.25, 0.5 and 1 microM) to investigate its cytotoxic mechanism. A progressive loss in cell viability together with a significant increase in the number of apoptotic and necrotic cells and lactate dehydrogenase release were seen in the experiment. Simultaneously, elevation of reactive oxygen species levels and intracellular [Ca(2+)]i, depletion of mitochondrial membrane potential and intracellular glutathione were revealed during the lead exposure. In addition, apoptotic morphological changes induced by lead exposure in rPT cells were demonstrated by Hoechst 33258 staining. The apoptosis was markedly prevented by N-acetyl-L-cysteine, while the necrosis was not affected. Moreover, catalase and superoxide dismutase activities in the living cells rose significantly. In conclusion, exposure of rPT cells to low-concentration lead led to cell death, mediated by an apoptotic and a necrotic mechanism. The apoptotic death induced by oxidative stress was the chief mechanism. Meanwhile, a group of cells survived lead action, mediated by their ability to activate antioxidant defense systems.
College of Veterinary Medicine, Yangzhou University, Yangzhou, People's Republic of China.
Lin
L
Wang
Heng
H
Wang
Maozhi
M
Hu
Jin
J
Cao
Dawei
D
Chen
Zongping
Z
Liu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D006690:Bisbenzimidazole / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007854:Lead / Q000378:metabolism* / Q000633:toxicity*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009336:Necrosis / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
D005456:Fluorescent Dyes; D017382:Reactive Oxygen Species; D007854:Lead; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D006690:Bisbenzimidazole; D002118:Calcium