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• W2159149748 abstract "Aminoglycoside antibiotics are known to be transported and accumulated within lysosomes of renal proximal tubular cells and to cause proximal tubular cell injury and necrosis. The pathogenesis of aminoglycoside nephrotoxicity is postulated to be related to the capacity of these organic polycations to interact electrostatically with membrane anionic phospholipids and to disrupt membrane structure and function. Aminoglycoside antibiotics have been shown to bind to anionic phospholipids of model membranes and to alter membrane permeability and promote membrane aggregation. In vivo these drugs induce phospholipiduria and a renal cortical phospholipidosis. The latter reflects the accumulation of phospholipid-containing myeloid bodies within the lysosomal compartment consequent to aminoglycoside-induced inhibition of lysosomal phospholipases. The mechanism of drug-induced inhibition of phospholipases has been shown to be secondary to the binding of these cationic drugs to anionic phospholipids. As the lysosomes became progressively distended with myeloid bodies, they become unstable and eventually rupture, which results in the release of acid hydrolases as well as high concentrations of aminoglycosides into the cytoplasm where they interact with and disrupt the function of other membranes and organelles including mitochondria and microsomes. It is postulated that the redistribution of drug from the lysosomal compartment to organellar membranes is the critical event which triggers the irreversible injury cascade. Polyaspartic acid is a polyanionic peptide which when administered in vitro or in vivo forms electrostatic complexes with aminoglycoside antibiotics and prevents these drugs from interacting with anionic phospholipids, from perturbing phospholipid metabolism and from causing cell injury and necrosis." @default.
• W2159149748 created "2016-06-24" @default.
• W2159149748 creator A5011528111 @default.
• W2159149748 date "1992-01-01" @default.
• W2159149748 modified "2023-10-14" @default.
• W2159149748 title "Drug-Phospholipid Interactions: Role in Aminoglycoside Nephrotoxicity" @default.
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• W2159149748 doi "https://doi.org/10.3109/08860229209106642" @default.
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