Nephrotoxicant inhibition of renal proximal tubule cell
regeneration.
Counts, Rachel S., Grayna Nowak, Roger D. Wyatt, and Rick G.
Schnellmann.
Department of Physiology and Pharmacology, College of Veterinary
Medicine, University of Georgia, Athens, GA 30602-7389 and Division
of Toxicology, University of Arkansas for Medical Sciences, 4301 W.
Markham, Slot 638, Little Rock, AR 72205-7199 and Department of
Poultry Science, College of Agricultural and Environmental Sciences,
University of Georgia, Athens, GA 30602
APStracts 2:0058F, 1995.
While nephrotoxicants have been shown to have direct lethal effects on
renal proximal tubule cells (RPTC), little is known concerning their
effects on the renal regenerative process. Additionally, the
mechanisms of RPT regeneration are still not clear. To examine these
issues an in vitro model of mechanically-induced injury to primary
cultures of rabbit RPTC was developed, and the effects of EGF, TGF
-[beta]1, and nephrotoxicants on the regenerative process were
examined. Experiments demonstrated that confluent monolayers swiped
with a 4 mm teflon policeman regenerated with 77% closure of the
swipe in 7 days. DNA content in swiped monolayers increased, reached
a maximum on day 3 (1.4-fold), and remained constant through day 7.
EGF accelerated regeneration and resulted in 96% swipe closure on day
7, and increased DNA content 2.3-fold. TGF-[beta]1 inhibited
regeneration and resulted in 22% swipe closure on day 7, but did not
inhibit the increase in DNA content. 5-fluorouracil (5-FU) inhibited
regeneration and resulted in 27% swipe closure on day 3 compared to
46% in the controls, and inhibited the increase in DNA content.
Mercuric chloride, fumonisin B1, and dichlorovinyl-L-cysteine, at
concentrations < 50 % of their lethal concentration, inhibited
regeneration and resulted in swiped areas 3.7, 4.2, and 2.1 times
larger, respectively, than controls on day 7. t-Butyl hydroperoxide,
at concentrations < 50 % of its lethal concentration, had no effect
on swipe closure. These results suggest that proliferation and
migration/spreading are important mechanisms in the regeneration
process, that EGF expedites the regeneration, and that certain
nephrotoxicants may contribute to renal dysfunction by inhibiting the
RPT regeneration.
Received 7 July 1994; accepted in final form 3 April 1995.
APS Manuscript Number F233-4.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 25 April 1995.