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Mechanisms of Zinc Oxide Nanoparticle (ZONP)‐Induced Alveolar Epithelial Cell (AEC) Injury
Author(s) -
KIM YONG HO,
FAZLOLLAHI FARNOOSH,
YACOBI NAZANIN R,
BOROK ZEA,
KIM KWANGJIN,
CRANDALL EDWARD D
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.612.17
Subject(s) - intracellular , lactate dehydrogenase , chemistry , reactive oxygen species , oxidative stress , mitochondrion , cell , zinc , cell injury , microbiology and biotechnology , biochemistry , apoptosis , biology , enzyme , organic chemistry
We investigated ZONP (20 nm diameter) induction of AEC injury utilizing primary rat alveolar epithelial cell monolayers (RAECM). We assessed injury by measuring transmonolayer resistance (R T ) and equivalent short‐circuit current (I EQ ), lactate dehydrogenase (LDH) release, intracellular reactive oxygen species (ROS) and mitochondrial activity. We also investigated effects of free Zn 2+ released from ZONP on R T and I EQ of RAECM. Results showed that apical exposure to 176 μg/mL ZONP decreased R T and I EQ of RAECM by 100% over 24h, whereas exposure to 11 μg/mL ZONP had little effect. Apical exposure of RAECM for 24h to 176 μg/mL ZONP caused irreversible injury. ZONP effects on R T yielded a half‐maximal concentration of 17 μg/mL. About 8 μg/mL of Zn 2+ was found to be released from 176 μg/mL ZONP suspension over 24h. When an equivalent concentration of Zn 2+ (as ZnCl 2 ) or supernatant from 24h ZONP suspensions was used to apically expose RAECM, R T was decreased by ~45% after 24h. Apical exposure for 24h to 176 μg/mL ZONP increased LDH release, disrupted cell plasma membrane integrity, decreased mitochondrial activity and increased intracellular ROS production. These data indicate that apical ZONP exposure of RAECM leads to severe cellular injury involving increased oxidative stress and disruption of cell membrane integrity, effects due in part to free Zn 2+ released from ZONP. (Funded by: NIH; Hastings & Whittier Foundations.)