Linked Life Data

2243355

Source:http://linkedlifedata.com/resource/pubmed/id/2243355

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1990-12-31
pubmed:abstractText
Coadministration of polyaspartic acid protects rats against aminoglycoside-induced nephrotoxicity, with respect to functional and pathological changes as well as to early signs of renal alterations (lysosomal phospholipidosis of proximal tubular cells, increased proliferation of proximal tubular and peritubular cells), without reduction, but actually by increasing the drug cortical content (Williams et al., J. Pharmacol. Exp. Ther. 237: 919, 1986; Gilbert et al., J. Infect. Dis. 159: 945, 1989; Beauchamp et al., 1990). Because aminoglycoside accumulation in kidney cortex involves their segregation in lysosomes, we have examined the possibility of formation of intracellular aminoglycoside-polyaspartic acid complexes that would render the drug less toxic. We found that in vitro polyaspartic acid (MW 9-15,000) 1) binds gentamicin with an optimum at acidic pH (5.4), 2) displaces it from negatively charged liposomes and 3) restores the activity of gentamicin-inhibited lysosomal phospholipase A1 toward phosphatidylcholine included in negatively charged liposomes. In parallel, we also observed that at pH 7.0, polyaspartic acid binds and displaces gentamicin from purified brush-border membrane vesicles, causing an apparent decrease of affinity of gentamicin for these membranes, which was falsely interpreted by Williams et al., J. Pharmacol. Exp. Ther. 237: 919, 1986 as "competition for a common membrane binding site." Assuming that, after its administration in vivo, polyaspartic acid gains access to lysosomes of proximal tubular cells, as many low molecular weight proteins and polypeptides do, our results suggest that protection against gentamicin-induced nephrotoxicity is obtained by the binding of the aminoglycoside to the polyanion in lysosomes, preventing thereby the development of phospholipidosis and therefore interfering with the cascade of events leading from drug accumulation to nephrotoxicity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
255
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
867-74
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Mechanism of protection afforded by polyaspartic acid against gentamicin-induced phospholipidosis. I. Polyaspartic acid binds gentamicin and displaces it from negatively charged phospholipid layers in vitro.
pubmed:affiliation
Laboratoire de Chimie Physiologique, Université Catholique de Louvain, Bruxelles, Belgium.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't