Carboxylate microsphere-induced cellular toxicity in human lung fibroblasts.
Carboxylate microspheres (CMs) are mainly used in industrial, biomedical and various household products. In this study, we assessed the cytotoxic effects of CMs on human MRC-5 lung fibroblasts by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Oxidative stress was determined by measurements of reactive oxygen species and antioxidant (superoxide dismutase and catalase) levels and proinflammatory cytokines quantified by enzyme-linked immunosorbent assay. Morphological changes were examined by light microscopy, confocal microscopy and transmission electron microscopy. The lung fibroblasts were exposed to increasing concentrations of CMs (0.1-1000 μmol/L) for 24 h. The results showed significant changes in cell morphology with induction of cytotoxicity and oxidative stress observed in 10-1000 μmol/L concentrations of CM-treated fibroblasts. Ultrastructural examination revealed the presence of CMs inside the cytoplasm of treated lung fibroblasts. CMs also induced elevated interleukin (IL)-1, IL-6, IL-8, IL-10 and tumor necrosis factor α levels at higher concentrations. We have demonstrated that CMs significantly reduce cell viability in a dose-dependant manner in lung fibroblasts at 0.1-1000 μmol/L doses. The findings suggest that high doses of CMs have the potential to induce cellular toxicity to the lung in vitro.
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore - 117597. rperumalsamy@yahoo.co.uk
Ramar Perumal
RP
Samy
Cheng-Teng
CT
Ng
Boon-Huat
BH
Bay
Frank
F
Watt
D017209:Apoptosis / Q000187:drug effects*; D002264:Carboxylic Acids / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008863:Microspheres; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D002264:Carboxylic Acids; D016207:Cytokines; D017382:Reactive Oxygen Species; D002374:Catalase; D013482:Superoxide Dismutase