The combination of ultrafine carbon black and lead provokes cytotoxicity and apoptosis in mice lung fibroblasts through oxidative stress-activated mitochondrial pathways

Abstract

Ultrafine particulates (UFPs) are considered one of the most hazardous of all air pollutants, which can be directly inhaled into the human body and cause direct damage to lung tissues. Lung fibroblasts (LF) play an important role in the structure and function of lung and there are few studies on primary cells at present. So, the article focuses on LF as the research objective and ultrafine carbon black (UFCB) and Pb-UFCB (loaded with lead) as a representative of UFPs to study the effect on LF. The results showed that UFCB and Pb-UFCB inhibited LF proliferation due to cell cycle arrested in the S phase, and induced apoptosis. Additionally, UFCB or Pb-UFCB could induce oxidative stress manifested as the increase of intracellular reactive oxygen species. The redox imbalance was further confirmed by measuring the changes of related enzymes, including the activity of superoxide dismutase and catalase and the level of reduced glutathione and malondialdehyde in cells. Moreover, the elevated lactate dehydrogenase in the culture medium indicated that cell membrane had been injured. And mitochondrial function was impaired by the imbalance of ATP synthesis and hydrolysis. In summary, both induced oxidative stress, which is the main driving force of LF early apoptosis, disruption of cell membrane integrity and mitochondrial function. Here, we provide a meaningful and challenging subject to explore the toxic effect and mechanism between UFPs and lung tissue at cellular levels, and theoretical basics for the possible changes of lung tissue function in vivo.

Keywords: Apoptotic; Cell cycle; Mice lung fibroblasts; Oxidative stress; Pb-UFCB; UFCB.