Proximal tubule aminoglycosides

Chatteijee et al., 1984 Sens et al., 1988), and cyclosporine (TrifiUis et al., 1984). Studies reported by Tay et al. (1988) in rabbit proximal tubule cultures with cisplatin revealed biochemical effects upon DNA synthetic activty that correlated with in vivo histochemical effects of this antitumor agent in animals. With respect to studies involving mercuric chloride and aminoglycoside antibiotics in primary renal cultures, light and electron microscopy revealed similar patterns of cellular pathology in vitro as compared to in vivo exposure in animals (Chatteijee et al., 1984 Aleo et al., 1987). 

Sens, M.A., Hennigar, G.R., Hazen-Martin, D.J. and Sens, D.A. (1988). Cultured human proximal tubule cells as a model for aminoglycoside nephrotoxicity. Ann. Clin. Lab. Set 18 204-214. 

Gentamicin is more toxic to LLC-PKj monolayers when exposed at the apical side, indicating a preferential uptake from the luminal membrane [136]. The uptake mechanism is proposed to be via megalin mediated endocytosis, a protein which is abundantly expressed in the proximal tubule [137]. A pathway delineated in LLC-PKl cells is proposed, whereby internalized aminoglycosides and other small molecular weight cationic compounds are transported from the early and late endosomes, through the Golgi complex. 

El-Mouedden M, Laurent G, Mingeot-Leclercq MP, Taper HS, Cumps J, Tulkens PM, Apoptosis in renal proximal tubules of rats treated with low doses of aminoglycosides, Antimicrob Agents Chemotherap, 2000,44(3) 665-75. 

Schwertz DW, Kreisberg Jl, Venkatachalam, Effects of aminoglycosides on proximal tubule brush border membrane phosphati-dylinositol-specific phospholipase C, J Pharmac and ExpTherap, 1984,231(1) 48-55. 

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