Laomettachit T, Puri I K, Liangruksa M
Bioinformatics and Systems Biology Program, School of Bioresources and Technology, King Mongkut's University of Technology Thonburi, Bangkok 10150, Thailand; Theoretical and Computational Physics (TCP) Group, King Mongkut's University of Technology Thonburi, Bangkok 10150, Thailand.
Department of Mechanical Engineering, McMaster University, Hamilton, ON L8S 4L7, Canada; School of Biomedical Engineering, McMaster University, Hamilton, ON L8S 4L7, Canada.
Toxicol Appl Pharmacol. 2017 Nov 1;334:47-54. doi: 10.1016/j.taap.2017.08.018. Epub 2017 Sep 1.
We examine the toxicity of titanium dioxide (TiO) nanoparticles on human liver through a two-step approach, including a physiologically-based pharmacokinetic (PBPK) model and a cell-response model. The PBPK model predicts the bio-distribution of nanoparticles that remain in the human body after exposure, with special attention to their accumulation in liver tissue. The cell-response model predicts liver cell death as a consequence of the accumulated TiO nanoparticles by considering cell fate dynamics through the interplay between cellular uptake of the nanoparticles and their dilution due to cell division. The results suggest that tissue damage from a low nanoparticle dose is negligible due to renewal cell division, but for higher doses larger fractions of cells must participate in the cell cycle to recover the original tissue mass. By combining the two models, it becomes possible to explain the liver cell viability and cell death after TiO nanoparticle exposure.
我们通过两步法研究二氧化钛（TiO）纳米颗粒对人体肝脏的毒性，该方法包括基于生理学的药代动力学（PBPK）模型和细胞反应模型。PBPK模型预测暴露后残留在人体中的纳米颗粒的生物分布，特别关注它们在肝组织中的积累。细胞反应模型通过考虑纳米颗粒的细胞摄取与其因细胞分裂而稀释之间的相互作用所导致的细胞命运动态，预测积累的TiO纳米颗粒导致的肝细胞死亡。结果表明，由于细胞更新分裂，低剂量纳米颗粒造成的组织损伤可忽略不计，但对于较高剂量，更大比例的细胞必须参与细胞周期以恢复原始组织质量。通过结合这两个模型，可以解释TiO纳米颗粒暴露后肝细胞的活力和细胞死亡情况。
