alexa Neonatal Clara cell toxicity by 4-ipomeanol alters bronchiolar organization in adult rabbits.
Toxicology

Toxicology

Journal of Environmental & Analytical Toxicology

Author(s): SmileyJewell SM, Nishio SJ, Weir AJ, Plopper CG, SmileyJewell SM, Nishio SJ, Weir AJ, Plopper CG

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Abstract Nonciliated bronchiolar (Clara) cells metabolize environmental toxicants, are progenitor cells during development, and differentiate postnatally. Because differentiating Clara cells of neonatal rabbits are injured at lower doses by the cytochrome P-450-activated cytotoxicant 4-ipomeanol than are those of adults, the impact of early injury on the bronchiolar epithelial organization of adults was defined by treating neonates (3-21 days) and examining them at 4-6 wk. Bronchiolar epithelium of 6-wk-old animals treated on day 7 was most altered from that of control animals. Almost 100\% of the bronchioles were lined by zones of squamous epithelial cells. Compared with control animals, the distal bronchiolar epithelium of 4-ipomeanol-treated animals had more squamous cells (70-90 vs. 0\%) with a reduced overall epithelial thickness (25\% of control value), fewer ciliated cells (0 vs. 10-20\%), a reduced expression of Clara cell markers of differentiation (cytochrome P-4502B, NADPH reductase, and 10-kDa protein), and undifferentiated nonciliated cuboidal cell ultrastructure. We conclude that early injury to differentiating rabbit Clara cells by a cytochrome P-450-mediated toxicant inhibits bronchiolar epithelial differentiation and greatly affects repair.
This article was published in Am J Physiol and referenced in Journal of Environmental & Analytical Toxicology

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