Increased renal DNA synthesis in vivo after administration of low doses of gentamicin to rats

Laurent, Guy; Maldague, Pierre; Carlier, Marianne; Tulkens, Paul M.

doi:10.1128/aac.24.4.586

Cited by 89 publications

(55 citation statements)

References 22 publications

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“…Shortly after their injection, these drugs locate sequentially on the brush border membrane of proximal tubular cells (1,25), on the membranes of endocytic vacuoles, and into the matrixes of small lysosomes of proximal tubular cells (1). They accumulate into the lysosomes of these cells (1,13,25), where they induce a lysosomal phospholipidosis characterized by the inhibition of phospholipase activities (19) and a postnecrotic cellular regeneration (20).…”

mentioning

confidence: 99%

Daptomycin may attenuate experimental tobramycin nephrotoxicity by electrostatic complexation to tobramycin

Couture

Simard

Gourde

et al. 1994

Antimicrob Agents Chemother

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). In an attempt to explain these results, the in vivo and in vitro interactions between daptomycin and tobramycin were studied. Tobramycin alone and preincubated with negatively charged phospholipid bilayers (liposomes) was dialyzed against increasing concentrations of daptomycin in buffer at pH 5.4. A significant drop in the concentration of tobramycin was observed when daptomycin was added to the opposite half cells. Furthermore, daptomycin induced a concentration-dependent release of lipid-bound tobramycin. Gold labeling experiments showed that daptomycin could be incorporated into phospholipid layers. Female Sprague-Dawley rats were treated with daptomycin alone, with tobramycin alone, or with the combination over 2 to 10 days. Levels of daptomycin and tobramycin in serum were similar in all groups. The levels of tobramycin in the renal cortex increased significantly with time and, on day 10, reached values of 654 ± 122 and 844 ± 298 ,ug/g of tissue (mean ± standard deviation; not significant) in animals treated with tobramycin and the combination of daptomycin-tobramycin, respectively. No significant difference was observed in the levels of tobramycin in the kidneys between animals treated with tobramycin or the daptomycin-tobramycin combination at any time. By contrast, daptomycin levels were significantly higher in the renal cortexes of animals treated with daptomycin-tobramycin in comparison with those in the renal cortexes of animals treated with daptomycin alone on days 6, 8, and 10 (P < 0.01). For immunogold labeling studies, animals were killed 4 h after a single injection of daptomycin alone or daptomycin in combination with tobramycin. Daptomycin was found throughout the matrixes of the lysosomes of proximal tubular cells of animals treated with daptomycin alone. In animals treated with the combination of daptomycin and tobramycin, daptomycin was associated with intralysosomal myeloid bodies. Our results suggest that daptomycin might attenuate experimental aminoglycoside nephrotoxicity by interacting with the aminoglycoside, perhaps electrostatically, and thereby protecting intracellular targets of toxicity.

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mentioning

confidence: 99%

Daptomycin may attenuate experimental tobramycin nephrotoxicity by electrostatic complexation to tobramycin

Couture

Simard

Gourde

et al. 1994

Antimicrob Agents Chemother

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“…The present study used a model of short term infusion in order to ensure that the intracortical uptake of aminoglycoside was not disturbed by the cellular necrosis and post necrotic regeneration usually observed during conventional therapy (20). The linear uptake of gentamicin observed in normal kidneys has also been reported earlier over the same range of serum levels (10,13,21).…”

Section: Discussionmentioning

confidence: 79%

Effect of Enterococcus faecalis Pyelonephritis on the Intracortical Accumulation Kinetics of Gentamicin in Rats

Jullien

Thériault

Bergeron

et al. 1990

Canadian Journal of Infectious Diseases and Medical Microbiolog

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ABSTRACT:The role of serum levels on the intracortical accumulation kinetics of gentamicin was evaluated in normal and Enterococcus jaecalis-infected kidn eys using a short term infusion model in conscious rats. Female Sprague-Dawley rats were infused over a period of 6 h with gentamicin achieving individual steady-state serum levels ranging from 0.5 to 20 11g/mL. Pyelonephritis was induced by a direct inoculation of the left kidney with a suspension of E jaecalis. This model resulted in severe infection of the left kidney and mild infection of the right kidney. Gentamicin cortical concentrations were analyzed as a function of serum levels by linear regression (least squares regression analysis). A MINOGLYCOSIDES ARE ESSENTIALLY ELIMINATEDby glomerular filtration and partially reabsorbed and accumulated by proximal tubular cells. Several factors have been recognized which disturb the normal intrarenal pharmacokinetics of gentamicin, eg. impaired renal function ( 1), glomerulonephritis (2). ischemia (3), state of hydration (4), diabetes (5) and renal infection (6).Beauchamp et al (7) and Bergeron et al (6) observed higher intracortical gentamicin concentrations in Escherichia coli-infected kidneys compared to normal kidneys. These changes, observed in the presence of Gram-negative infection, 654-2705. Fax (418) Received for publication February 27, 1990 were more severe than those observed in kidneys infected with Enterococcusjaecalis (8). There has been speculation that endotoxin might have been responsible for the disturbed intrarenal distribution of aminoglycoside in E coli pyelonephritis. In fact., Bergeron and Bergeron (9) showed that endotoxin increases the level of aminoglycoside in the renal parenchyma compared to normal, while the tissue levels of cephalothin were not modified.More recently, Beauchamp et al (10) showed that the intracortical accumulation kinetics of gentamicin was modified in the presence of E coli pyelonephritis. The aim of the present study was to evaluate the effect of E faecalis pyelonephritis on the intracortical accumulation kinetics of gentamicin using a short term infusion model in conscious rats. and 265 g were used. They had free access to food and water throughout the experiment. Two groups of animals were studied: normal (n=22) and pyelonephritic (n=23) rats. Pyelonephritis was induced four days before perfusion . Animals were anesthetized with 350 mg/kg chloral hydrate, and their left sides were shaved. An incision was made at the level of the left kidney and the kidney was exposed and in~ected with 0 . 1 mL of an inoculum containing 10 to 10 8 Ejaecalis (ATCC 23241) . The gentamicin minimal inhibitory and minimal bactericidal concentrations for the strain were 32 and 128~-tg/mL, r espectively. The suspension was injected directly into the medulla through the upper and lower poles of the kidney, as described by Kaye (11). This inoculation produces two kinds of infection: a serious pyelonephritis of the left kidney and a less severe infection of the right kidney due to...

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“…This may indicate that the tubular epithelial cell of the F344 is more sensitive to aminoglycoside-induced toxicity and/or, the capacity of their renal tubular epithelial cell to regenerate is less than that of the Sprague-Dawley. This possible difference in tubular regenerative capacity would be an important area to investigate employing DNA studies similar to those performed by Laurent et a1 (17).…”

Section: Discussionmentioning

confidence: 99%

Differences in the Sensitivity of Fischer and Sprague-Dawley Rats to Aminoglycoside Nephrotoxicity

1991

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ABSTRACXBecause of the anecdotal but unconfirmed inferences of the greater sensitivity of Fischer rats to aminoglycoside nephrotoxicity, an intrastudy comparison of the sensitivity of Fischer and Sprague-Dawley rats to aminoglycoside nephrotoxicity was undertaken. Tobramycin was administered at 3 dose levels to each strain of rat for 10 days. Nephrotoxicity was evaluated utilizing a spectrum of both functional and morphologic assessments of renal proximal tubular integrity. The results confirm that the aged matched Fischer rat is more sensitive to the nephrotoxic effect of tobramycin than the Sprague-Dawley. These results also suggest an opportunity to study quantitative and perhaps qualitative differences in pathogenic mechanisms of aminoglycoside nephrotoxicity in a single laboratory animal species.

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Increased renal DNA synthesis in vivo after administration of low doses of gentamicin to rats

Cited by 89 publications

References 22 publications

Daptomycin may attenuate experimental tobramycin nephrotoxicity by electrostatic complexation to tobramycin

Daptomycin may attenuate experimental tobramycin nephrotoxicity by electrostatic complexation to tobramycin

Effect of Enterococcus faecalis Pyelonephritis on the Intracortical Accumulation Kinetics of Gentamicin in Rats

Differences in the Sensitivity of Fischer and Sprague-Dawley Rats to Aminoglycoside Nephrotoxicity

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