HWA-448 reduces gentamicin toxicity in LLC-PK1 cells

D. M. Ford, R. E. Thieme, C. A. Lamp, S. J. Covington, Bruce Molitoris

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

An LLC-PK1 cell culture model was used to evaluate for a direct protective effect of the pentoxifylline analogue HWA-448 in gentamicin nephrotoxicity at the cellular level. Cells exposed to 2 mM gentamicin for 6 days displayed a significant decrease in specific activities of leucine aminopeptidase, NaK ATPase, and N-acetyl glucosaminidase, and an increase in total cellular phospholipids (P <.05). Concomitant exposure to 0.125 mM HWA- 448, a dose that did not alter cellular enzymes or total phospholipids under physiologic conditions, prevented the alterations in marker enzymes and total phospholipids induced by gentamicin (P <.05). Gentamicin binding and uptake studies revealed 0.125 mM HWA-448 had no effect on LLC-PK1 cell plasma membrane binding or cellular gentamicin uptake. We conclude that HWA-448 ameliorates gentamicin-induced alterations in LLC-PK1 cell enzymes and phospholipids by a mechanism independent of plasma membrane binding or cellular uptake.

Original languageEnglish (US)
Pages (from-to)29-33
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Volume274
Issue number1
StatePublished - 1995
Externally publishedYes

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LLC-PK1 Cells
Gentamicins
Phospholipids
Cell Membrane
Enzymes
Leucyl Aminopeptidase
Hexosaminidases
Pentoxifylline
Adenosine Triphosphatases
torbafylline
Cell Culture Techniques

ASJC Scopus subject areas

  • Pharmacology

Cite this

Ford, D. M., Thieme, R. E., Lamp, C. A., Covington, S. J., & Molitoris, B. (1995). HWA-448 reduces gentamicin toxicity in LLC-PK1 cells. Journal of Pharmacology and Experimental Therapeutics, 274(1), 29-33.

HWA-448 reduces gentamicin toxicity in LLC-PK1 cells. / Ford, D. M.; Thieme, R. E.; Lamp, C. A.; Covington, S. J.; Molitoris, Bruce.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 274, No. 1, 1995, p. 29-33.

Research output: Contribution to journalArticle

Ford, DM, Thieme, RE, Lamp, CA, Covington, SJ & Molitoris, B 1995, 'HWA-448 reduces gentamicin toxicity in LLC-PK1 cells', Journal of Pharmacology and Experimental Therapeutics, vol. 274, no. 1, pp. 29-33.
Ford, D. M. ; Thieme, R. E. ; Lamp, C. A. ; Covington, S. J. ; Molitoris, Bruce. / HWA-448 reduces gentamicin toxicity in LLC-PK1 cells. In: Journal of Pharmacology and Experimental Therapeutics. 1995 ; Vol. 274, No. 1. pp. 29-33.
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