Pathophysiologic Mechanisms in Aminoglycoside Nephrotoxicity

Whelton, Andrew; Solez, Kim

doi:10.1002/j.1552-4604.1983.tb01791.x

Cited by 13 publications

(5 citation statements)

References 22 publications

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“…The noted functional and pathological modifications found then were very similar to those observed in adults, i.e. mainly a decrease in creatinine clearance and lesions of proximal tubule cells [5,6,18,25], but the GBM was not investigated.…”

Section: Discussionmentioning

confidence: 65%

“…Nevertheless, the relationship of gentamicin excre tion to post-conceptual age is well established [16], and it is known that infants treated with recommended dosages 1 A preliminary account of this work was published as an abstract in ref. [26].are at risk of gentamicin accumulation [17][18][19], It has been reported that the developing rat kidney was altered after treatment of the pregnant mother with aminoglycosides [20][21][22][23]: neonate kidneys presented lesions of the tubules quite similar to those observed in adults [24,25], and, surprisingly, they also exhibited alterations of both ma ture and immature glomeruli [26]. It has also been shown in rats that after prenatal exposure to gentamicin the amount of differentiated nephrons at birth was lower than in controls [22,27], Drug effects on renal maturation are not yet well known [12,[28][29][30], and the possibility that developing glomeruli could be altered either in quality and/or in number could have consequences in later life.…”

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confidence: 99%

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Glomerular Alterations in Rat Neonates after Transplacental Exposure to Gentamicin

Smaoui

Mallié²,

Cheignon³

et al. 1991

Nephron

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Alterations of tubules and glomerules have been reported previously in kidneys of rat neonates after aminoglycosides were given to the mother during gestation. Here, we have studied the effects of gentamicin on the development of the glomerular basement membrane (GBM). Pregnant Wistar female rates were treated with gentamicin. Deliveries occurred normally. Using electron microscopy, we looked at the deepest glomerules of the kidneys of 1-day-old neonates: myeloid bodies were found in podocytes, and the GBM appeared thicker and denser than in controls. Anionic ferritin, injected intravenously crossed the GBM in prenatally gentamicin-exposed animals, but not in controls. Furthermore, urine electrophoresis showed the presence of proteins normally found only in the urine of fetuses 2 days before birth. We suggest then, that in utero exposure to gentamicin leads to a delay of renal maturation and that the GBM is altered in juxtamedullary nephrons while it is normally differentiated and functioning in controls. Thus exposure to drugs before birth could be harmful to the GBM.

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Section: Discussionmentioning

confidence: 65%

mentioning

confidence: 99%

Glomerular Alterations in Rat Neonates after Transplacental Exposure to Gentamicin

Smaoui

Mallié²,

Cheignon³

et al. 1991

Nephron

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“…Previous studies reported that in acute tubular necrosis, tubular injury is mainly responsible for the reduced glomerular filtration. It was also suggested that the tubular abnormalities involved are blockage of tubules causing backward flow of glomerular filtrate [30]. Thus, renal insufficiency in TAA-treated rats might be secondary to ROS [31].…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Reverses Thioacetamide-Induced Renal Assault with respect to Oxidative Stress, Renal Function, DNA Damage, and Cytokine Release in Wistar Rats

Zargar

Alonazi

Rizwana

et al. 2019

Oxidative Medicine and Cellular Longevity

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Background. Thioacetamide (TAA), a class 2B-type carcinogen, is a potent toxicant. Toxicities caused by this compound in various tissues due to oxidative stress, increase of proinflammatory markers, and apoptosis have been reported; however, reports on kidney toxicity are negligible. Resveratrol (RSV), on the other hand, has demonstrated antioxidant and anti-inflammatory effects in different cases. Resveratrol’s protective effects against TAA kidney toxicity were investigated in four rat groups. Methodology. Four groups of rats were studied as follows (n=8): control group, where rats were fed normal diet and water; TAA group, where rats received 0.3% TAA in water for two weeks; RSV group, where rats received 10 mg/kg body weight (bw) of RSV as oral suspension for two weeks; and treated group, where rats orally received 10 mg/kg bw RSV and simultaneously received 0.3% TAA for two weeks. Kidney homogenates from all groups were analyzed for cytokine release (IL-4, TNF-α, and IFN-γ) and oxidative stress (lipid peroxidation, catalase, and 8-OHdG). The serum of rats was analyzed for the quantification of renal function markers (blood urea nitrogen (BUN), creatinine, and creatine kinase). Result. A significant increase in the renal function markers (BUN, 240%; creatinine, 187%; and creatine kinase, 117%), oxidative stress parameters (lipid peroxidation, 192% increase; catalase, 30.5% decrease), cytokines (IL-4, 120%; TNF-α, 129%; and IFN-γ, 133%), and DNA damage was observed in the TAA-treated group. All changes were significantly reversed in the group treated with RSV and TAA (P<0.05) in combination, with no significant difference compared to the control group. Conclusion. We conclude that resveratrol shows protection against TAA toxicity in rat kidney with respect to DNA damage, oxidative stress, renal function and cytokine release.

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“…The nephrotoxic potential of aminoglycosides limits their clinical use (24), particularly in patients with pre-existing renal impairment. Rats are frequently used as models of aminoglycoside-induced nephrotoxicity (9); however, possible differences in strain sensitivity to nephrotoxicity has not been addressed in a systematic manner.…”

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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Pathophysiologic Mechanisms in Aminoglycoside Nephrotoxicity

Cited by 13 publications

References 22 publications

Glomerular Alterations in Rat Neonates after Transplacental Exposure to Gentamicin

Glomerular Alterations in Rat Neonates after Transplacental Exposure to Gentamicin

Resveratrol Reverses Thioacetamide-Induced Renal Assault with respect to Oxidative Stress, Renal Function, DNA Damage, and Cytokine Release in Wistar Rats

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

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