College of Veterinary Medicine, Yangzhou University, 12 East Wenhui Road, Yangzhou 225009, People's Republic of China.
Arch Environ Contam Toxicol. 2011 Oct;61(3):500-11. doi: 10.1007/s00244-011-9644-4. Epub 2011 Feb 2.
The combined effects of lead (Pb) and cadmium (Cd) on primary cultures of rat proximal tubular (rPT) cells were studied. These cells were either treated with Pb acetate (0.5 and 1 μM) alone, Cd acetate (2.5 and 5 μM) alone, or a combination of Pb and Cd acetate, and then joint cytotoxicity was evaluated. The results showed that the combination of these two metals decreased cell viability and increased the number of apoptotic and necrotic cells and lactate dehydrogenase release synergistically. Simultaneously, increased intracellular reactive oxygen species, malondialdehyde, and calcium levels and decreased mitochondrial membrane potential, intracellular acidification, and inhibition of Na(+), K(+)-, and Ca(2+)-ATPase activities were shown during the exposure. In addition, apoptotic morphological changes induced by these treatments in rPT cells were demonstrated by Hoechst 33258 staining. The apoptosis was markedly prevented by N-acetyl-L-cysteine, whereas necrosis was not affected. In summary, there was a synergistic cytototic effect of Pb combined with Cd on rPT cells. Cell death induced by Pb-Cd mixture was mediated by an apoptotic and a necrotic mechanism. Apoptotic death was the chief mechanism. Changes of intracellular events were intimately correlated with both oxidative stress and mitochondrial dysfunction, which promoted the development of apoptosis.
研究了铅（Pb）和镉（Cd）对大鼠近端肾小管（rPT）细胞原代培养物的联合作用。这些细胞单独用醋酸铅（0.5 和 1 μM）、醋酸镉（2.5 和 5 μM）或醋酸铅和镉的混合物处理，然后评估联合细胞毒性。结果表明，这两种金属的组合协同降低细胞活力并增加凋亡和坏死细胞的数量以及乳酸脱氢酶释放。同时，暴露过程中显示细胞内活性氧、丙二醛和钙水平增加，线粒体膜电位、细胞内酸化和 Na(+)、K(+)-和 Ca(2+)-ATP 酶活性抑制降低。此外，这些处理在 rPT 细胞中诱导的凋亡形态变化通过 Hoechst 33258 染色显示。N-乙酰-L-半胱氨酸明显阻止了细胞凋亡，而坏死不受影响。总之，Pb 与 Cd 联合对 rPT 细胞有协同的细胞毒性作用。Pb-Cd 混合物诱导的细胞死亡是通过凋亡和坏死机制介导的。凋亡死亡是主要机制。细胞内事件的变化与氧化应激和线粒体功能障碍密切相关，这促进了凋亡的发展。
