Changes in surface charge density on liposomes induced by Escherichia coli endotoxin

Onji, Toyoshi; Liu, Maw-Shung

doi:10.1016/0005-2736(79)90267-0

Cited by 21 publications

(8 citation statements)

References 10 publications

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“…Some investigators have also examined the physical properties of the membrane after interaction with LPS. The results have demonstrated that LPS interaction with phospholipid monolayers or bilayers is based on both hydrophobic and hydrophilic forces (2,30,37). The sequence of interaction, however, is not discernible from these studies.…”

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confidence: 77%

Characterization of lipopolysaccharide fractions and their interactions with cells and model membranes

Yeh

Jacobs

1992

J Bacteriol

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The role of the length of the 0-antigen polysaccharide side chain of bacterial lipopolysaccharide (LPS) Lipopolysaccharide (LPS) is a major component of the outer membrane of gram-negative bacteria. The structure of LPS, particularly that from members of the family Enterobacteriaceae, is composed of three well-defined structural regions: (i) the hydrophobic lipid A which anchors it in the outer leaflet of the outer membrane and has about seven fatty acid chains linked to the diglucosamine backbone, (ii) the core oligosaccharide, and (iii) the 0-antigen polysaccharide side chain. The polysaccharide extends into the cell surroundings (see references 5, 12, 15, 22, 23, and 36 for reviews). This structure is generally for a monomer unit in smooth strains of bacteria. However, because of its amphipathic nature, LPS in an aqueous solution exists as aggregates of macromolecular subunits. In addition, LPS from rough mutants is deficient in various amounts of core oligosaccharide.For bacteria, LPS seems to be important for maintaining the integrity of the microorganisms in an adverse environment and as a barrier against the entry of small molecules into the bacteria (24,28,40). On the other hand, LPS is responsible for inducing various pathophysiological effects in hosts, including fever, leukocytosis, hypotension, and toxic shock, which can lead to death (see references 25 and 26 for reviews). However, there is little information on the molecular basis of LPS interactions with cellular membranes.In the immune system LPS is a potent mitogen for bone marrow-derived lymphocytes (B cells) which are stimulated in vitro (6,32)

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mentioning

confidence: 77%

Characterization of lipopolysaccharide fractions and their interactions with cells and model membranes

Yeh

Jacobs

1992

J Bacteriol

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“…Hemodynamic changes resulting from endotoxin could also have disturbed the renal distribution of vancomycin. As endotoxin has been shown to increase the negative charge of biological membranes formed from different phospholipids, we cannot eliminate the possibility that it could have acted directly on the renal uptake of vancomycin (24). In fact, the binding between positively charged vancomycin and the negatively charged phospholipids could have been enhanced by endotoxin.…”

Section: Methodsmentioning

confidence: 97%

Intrarenal distribution of vancomycin in endotoxemic rats

Ngeleka

Auclair

Tardif

et al. 1989

Antimicrob Agents Chemother

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We previously observed that the intrarenal distribution of aminoglycosides was modified by Escherichia coli endotoxin in the absence of any major renal physiological disturbance or histological changes. In the present study, we evaluated the role of E. coli endotoxin on the intrarenal distribution of vancomycin. At the beginning of the experiment, female Sprague-Dawley rats were infused intravenously with saline (control) or endotoxin (0.25 mg/kg) during 15 min. Thereafter, saline was constantly infused for the following 4 h. Two hours after the beginning of the infusion, animals were injected intravenously with a single dose of vancomycin (20 mg/kg).The drug levels in serum; renal cortex, medulla, and papilla; and urine were evaluated from 0.08 to 24 h after injection. Analysis of the area under the curve of the drug concentration in the different kidney components versus time showed a higher accumulation of vancomycin in the renal cortex and medulla in the endotoxininfused rats than in the normal rats (P < 0.01). Endotoxin was associated with an increase in the half-life in serum (P < 0.01) and a lower elimination rate constant. The total clearance of vancomycin from plasma was significantly decreased in endotoxin-treated rats (P < 0.01). These results demonstrate that endotoxin modifies the renal handling of vancomycin.Vancomycin is a glycopeptide antibiotic with potent activity against gram-positive bacteria which may increase the nephrotoxic potential of aminoglycosides. The early preparation introduced in the 1950s had many impurities (14). During that period, although the nephrotoxic potential was not clearly established, up to 25% of patient were reported to have increased azotemia (29). When less toxic antistaphylococcal antibiotics, including the semisynthetic penicillins and cephalosporins, appeared, vancomycin use drastically diminished; but the emergence of methicillin-resistant staphylococci has prompted the resurgence of its use (27). The currently available compound has been purified and is believed to be less toxic than the parent compound. The incidence of nephrotoxicity with the new vancomycin has been less than 8% (11,23,27). In animals, large doses of antibiotics are needed to induce renal damage, and the mechanism of renal toxicity has not been determined. It seems that vancomycin accumulates within the renal parenchyma and induces an interstitial nephritis and proximal tubular necrosis.Endotoxin, an important constituent of the cell wall of gram-negative bacteria, has been classified as a major offender that is responsible for many complications associated with severe infections, including septic shock and renal failure. Endotoxin, which is liberated in infected patients and released in excess during antibiotic therapy (25), is able to modify the hemodynamic status of the host (13), to activate the immunological and inflammatory processes (6), to induce vasoconstriction (28), and to act directly on target cells and organelles to induce cell injuries (15,18).Previous experimental studies fr...

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“…Moreover, both endotoxins and aminoglycosides seem to have their receptor sites on phospholipids (1,19). Endotoxin seems to modify the total charge on the liposomes formed from different phospholipids (18). The link between tobramycin (a polycationic drug) and its receptors (phospholipids which become more negatively charged by endotoxin) could have become stronger in the presence of endotoxin, leading to an increased incorporation of the drug within the tubules.…”

Section: Discussionmentioning

confidence: 99%

Autoradiography of tobramycin uptake by the proximal and distal tubules of normal and endotoxin-treated rats

Bergeron¹,

Bergeron²,

Marois³

1986

Antimicrob Agents Chemother

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[3H]tobramycin was investigated. The accumulation of [3lHltobramycin in proximal tubules, distal tubules, and collecting ducts was compared in both normal and endotoxin-injected (0.25 mg/kg) rats. Histological observations were also made. IBlood pressure and cardiac frequency were recorded, and renal function was evaluated with labeled inulin and p-aminohippuric acid. Following administration of endotoxin, disturbed intrarenal localization of the drug was noted. Grain counts were affected in both proximal and distal tubules. Increased labeling was observed at all time intervals in the proximal tubules. In the distal tubules of endotoxemic animals we could detect higher amounts of drug at 10 and 60 min in the medulla and at 10 min in the cortex. Not all of the tubules were labeled to the same extent. No histological lesion was noted on light microscopy in animals receiving either normal saline or endotoxin. The dose of endotoxin used resulted in very fine physiological disturbance. Both blood pressure and cardiac frequency were minimally affected by endotoxin. Decreases in glomerular filtration rate and renal plasma flow were observed. However, none of these changes was statistically significant. The present study has shown that low doses of endotoxin alter the renal handling of aminoglycosides in the absence of any major physiological disturbance or histological changes. By increasing the total amount of drug within the kidney, endotoxin might increase the nephrotoxic potential of aminoglycosides.

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Changes in surface charge density on liposomes induced by Escherichia coli endotoxin

Cited by 21 publications

References 10 publications

Characterization of lipopolysaccharide fractions and their interactions with cells and model membranes

Characterization of lipopolysaccharide fractions and their interactions with cells and model membranes

Intrarenal distribution of vancomycin in endotoxemic rats

Autoradiography of tobramycin uptake by the proximal and distal tubules of normal and endotoxin-treated rats

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