HWA-448 reduces gentamicin toxicity in LLC-PK1 cells. 1995

D M Ford, and R E Thieme, and C A Lamp, and S J Covington, and B A Molitoris
Department of Pediatrics, Children's Hospital, University of Colorado Medical Center, Denver, USA.

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.

UI MeSH Term Description Entries
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D010431 Pentoxifylline A METHYLXANTHINE derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production. Agapurin,BL-191,Oxpentifylline,Pentoxil,Torental,Trental,BL 191,BL191
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D005839 Gentamicins A complex of closely related aminoglycosides obtained from MICROMONOSPORA purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit PROTEIN BIOSYNTHESIS. Gentamicin Sulfate (USP),Gentamycin,G-Myticin,Garamycin,Gentacycol,Gentamicin,Gentamicin Sulfate,Gentamycins,Gentavet,Genticin,G Myticin,GMyticin,Sulfate, Gentamicin
D000254 Sodium-Potassium-Exchanging ATPase An enzyme that catalyzes the active transport system of sodium and potassium ions across the cell wall. Sodium and potassium ions are closely coupled with membrane ATPase which undergoes phosphorylation and dephosphorylation, thereby providing energy for transport of these ions against concentration gradients. ATPase, Sodium, Potassium,Adenosinetriphosphatase, Sodium, Potassium,Na(+)-K(+)-Exchanging ATPase,Na(+)-K(+)-Transporting ATPase,Potassium Pump,Sodium Pump,Sodium, Potassium ATPase,Sodium, Potassium Adenosinetriphosphatase,Sodium-Potassium Pump,Adenosine Triphosphatase, Sodium, Potassium,Na(+) K(+)-Transporting ATPase,Sodium, Potassium Adenosine Triphosphatase,ATPase Sodium, Potassium,ATPase, Sodium-Potassium-Exchanging,Adenosinetriphosphatase Sodium, Potassium,Pump, Potassium,Pump, Sodium,Pump, Sodium-Potassium,Sodium Potassium Exchanging ATPase,Sodium Potassium Pump
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013552 Swine Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA). Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog
D018374 LLC-PK1 Cells Epithelial cell line originally derived from porcine kidneys. It is used for pharmacologic and metabolic studies. Cell, LLC-PK1,Cells, LLC-PK1,LLC PK1 Cells,LLC-PK1 Cell

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