HWA-448 reduces gentamicin toxicity in LLC-PK1 cells

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

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3 Scopus citations


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
Issue number1
StatePublished - Jan 1 1995
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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