Wang Lin, Wang Heng, Hu Maozhi, Cao Jin, Chen Dawei, Liu Zongping
College of Veterinary Medicine, Yangzhou University, Yangzhou, People's Republic of China.
Arch Toxicol. 2009 May;83(5):417-27. doi: 10.1007/s00204-009-0425-z. Epub 2009 Apr 4.
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.
铅是一种已知的肾毒性元素。在本研究中，用不同浓度的醋酸铅（0.25、0.5和1微摩尔）处理大鼠近端肾小管（rPT）细胞的原代培养物，以研究其细胞毒性机制。实验中观察到细胞活力逐渐丧失，同时凋亡和坏死细胞数量显著增加，乳酸脱氢酶释放也增加。同时，在铅暴露期间，活性氧水平和细胞内[Ca(2+)]i升高，线粒体膜电位和细胞内谷胱甘肽耗竭。此外，通过Hoechst 33258染色证实了铅暴露诱导的rPT细胞凋亡形态变化。N-乙酰-L-半胱氨酸可显著预防凋亡，而坏死不受影响。此外，活细胞中的过氧化氢酶和超氧化物歧化酶活性显著升高。总之，rPT细胞暴露于低浓度铅会导致细胞死亡，由凋亡和坏死机制介导。氧化应激诱导的凋亡死亡是主要机制。同时，一组细胞通过激活抗氧化防御系统的能力在铅作用下存活下来。
