Induction of apoptosis in rat lung epithelial cells by multiwalled carbon nanotubes.
Carbon nanotubes (CNTs), the most promising material with unique characteristics, find its application in different fields ranging from composite materials to medicine and from electronics to energy storage. However, little is known about the mechanism behind the interaction of these particles with cells and their toxicity. So, here we investigated the adverse effects of multiwalled CNTs (MWCNTs) in rat lung epithelial (LE) cells. The results showed that the incubation of LE cells with 0.5-10 microg/mL of MWCNTs caused a dose- and time-dependent increase in the formation of free radicals, the accumulation of peroxidative products, the loss of cell viability, and antioxidant depletion. The significant amount of incorporation of dUTPs in the nucleus after 24 h confirms the induction of apoptosis. It was also observed that there is an increase in the activity of both caspases-3 and caspase-8 in cells, with increases in time and the concentration of MWCNTs. No significant incorporation of dUTPs was observed in cells, incubated with z-VAD-fmk, which confirmed the role of caspases in DNA fragmentation. The present study reveals that MWCNTs induced oxidative stress and stimulated apoptosis signaling pathway through caspase activation in rat LE cell lines.
Ravichandran
Prabakaran
P
Molecular Toxicology Laboratory, Center for Biotechnology & Biomedical Sciences, Department of Biology, Norfolk State University, Norfolk, VA 23504, USA.
Periyakaruppan
Adaikkappan
A
Sadanandan
Bindu
B
Ramesh
Vani
V
Hall
Joseph C
JC
Jejelowo
Olufisayo
O
Ramesh
Govindarajan T
GT
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D005562:Formazans / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000166:cytology*; D037742:Nanotubes, Carbon / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013778:Tetrazolium Salts / Q000378:metabolism; D013997:Time Factors
D000975:Antioxidants; D005562:Formazans; D005609:Free Radicals; D037742:Nanotubes, Carbon; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; C079782:MTT formazan; D013482:Superoxide Dismutase; D053148:Caspase 3; D053181:Caspase 8; D005978:Glutathione