Uranyl Nitrate Induced Polyuric Acute Tubular Necrosis in Rats

Lim, In-Kyoung; Lee, Kee-Ho; Han, Byung-Don; Jang, Ja-Jun; Yun, Taik-Koo

doi:10.3349/ymj.1987.28.1.38

Cited by 12 publications

(8 citation statements)

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“…This also generally causes a corresponding increase in water intake, but this sometimes does not happen under septic conditions. Similar results have been described in several rat models of sepsis-induced renal failure and toxin-induced PARF (Lim et al, 1987;Heemskerk et al, 1996;Holly et al, 2006). Whereas the results obtained from the group given the 5.7 ϫ 10 12 VP/kg dose strongly suggest that kidney function is indeed compromised after adenovirus administration, data obtained from the 5.7 ϫ 10 11 VP/kg treatment group are not as conclusive.…”

Section: Le Et Al 1106supporting

confidence: 80%

Renal Pathophysiology After Systemic Administration of Recombinant Adenovirus: Changes in Renal Cytochromes P450 Based on Vector Dose

Boquet

Clark

et al. 2006

Human Gene Therapy

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Recombinant adenovirus (Ad) significantly alters hepatic cytochrome P450 (CYP). Because changes in renal function can alter hepatic CYP, the effect of Ad on renal CYPs 4A1, 4A2, 4F1, and 2E1 was evaluated. Male Sprague-Dawley rats were given one of six intravenous doses (5.7x10(6)-5.7x10(12) viral particles/kg [VP/kg]) of Ad expressing beta-galactosidase or saline. CYP protein, activity, gene expression, and serum creatinine (SCr) were evaluated 0.25, 1, 4, and 14 days later. Doses of 5.7x10(11) and 5.7x10(12) VP/kg increased CYP4A protein within 24 hr by 35 and 48%, respectively (p<0.05). A similar trend was observed on day 4. CYP4A1 mRNA doubled 6 hr after doses of 5.7x10(10)-10(12) VP/kg (p<0.01). Similar effects were observed 1 day after each dose tested. CYP4A2 gene expression was 20% above control 1 day after treatment with 5.7x10(10)-10(12) VP/kg and remained high through day 14. CYP4F1 expression was unaffected by all doses (p=0.08). CYP2E1 activity and gene expression were significantly suppressed 24 hr after administration of all doses and began to normalize by day 14 (p<0.01). SCr was significantly reduced (approximately 50%) throughout the study for doses at and below 5.7x10(11) VP/kg. SCr was increased by a factor of 3 by 5.7x10(12) VP/kg and glomerular filtration was significantly reduced (p<0.01). This suggests that changes in renal CYP and corresponding arachidonic acid metabolites may play a role in the documented toxicity associated with the systemic administration of recombinant Ad.

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Section: Le Et Al 1106supporting

confidence: 80%

Renal Pathophysiology After Systemic Administration of Recombinant Adenovirus: Changes in Renal Cytochromes P450 Based on Vector Dose

Boquet

Clark

et al. 2006

Human Gene Therapy

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“…Lim et al (1987) did not provide any EM evidence for the former azotemia explanation (reduced glomular filtration) reporting only that both tubular as well as glomular basement membranes remained intact. However, Haley et al (1982) did note on EM that glomular visceral epithelium pedicles were broad and flattened in support of direct glomular damage.…”

Section: Discussionmentioning

confidence: 71%

“…Ultrastructural examination by electron microscopy (EM) by Lim et al (1987) and Haley et al (1982) demonstrated numerous changes in tubular epithelial cells in support of the solute feedback azotemia explanation. Lim et al (1987) did not provide any EM evidence for the former azotemia explanation (reduced glomular filtration) reporting only that both tubular as well as glomular basement membranes remained intact.…”

Section: Discussionmentioning

confidence: 95%

“…Renal uranium concentration data were not provided, so values cannot be compared with those reported here. The very high doses of uranium used by Lim et al (1987) did not appear to result in mortality. In the present study, the degree of proximal tubular necrosis and associated elevations of serum creatinine and BUN concentrations peaked at day seven post-dosing in correlation with peak serum DU concentration.…”

Section: Renal Histopathologymentioning

confidence: 86%

“…This was noted on postdosing days 3 and 7, but was absent on day 30. DISCUSSION Uranium, as other heavy metals, is a well-known nephrotoxin, accumulating in the kidney and injuring proximal tubular epithelial cells, but preserving the basal lamina (Lim et al, 1987). Following absorption the metal is carried in the blood plasma as uranium-transferrin or in low molecular weight anionic complexes.…”

Section: Renal Histopathologymentioning

confidence: 99%

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Temporal Clinical Chemistry and Microscopic Renal Effects Following Acute Uranyl Acetate Exposure

Zimmerman

Barber²,

Ehrich

et al. 2007

Toxicol Pathol

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Military use of depleted uranium (DU) has renewed interest in the toxicology of this metal. In this study, the nephrotoxicity of single exposure DU was assessed with and without pre-exposure stress. Adult male Sprague-Dawley rats (n=288) were administered a single IM dose of 0, 0.1, 0.3 or 1.0 mg/kg DU. Corticosterone concentrations (ng/ml, mean+/-SD) were 763.65+/-130.94 and 189.80+/-90.81 for swim stressed and unstressed rats. Serum and kidney uranium concentration, hematocrit, chemistry, and renal histology were assessed on sacrifice days 1, 3, 7 and 30 post-DU-dosing. Dose related increases in serum and kidney uranium were noted. DU concentration peaked day 1 in the kidney and days 3-7, in the serum. Dose-related elevations of Cr and BUN concentrations were seen on days 3 and 7. A decline in serum albumin coincided with Cr and BUN suggesting protein losing nephropathy. Dose related acute tubular necrosis and proliferative glomulonephritis were seen. Tubular regeneration in low dose rats was almost complete by day 30. High dose rats had extensive tubular necrosis and delayed regeneration with focal residual chronic interstitial nephritis and cortical scarring. Glomular changes were reversed in all treatment groups by day 30. Stress exposure had no impact on any measured renal parameter.

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