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Bismuth overdosing-induced reversible nephropathy in rats
B T Leussink1, A Slikkerveer, M R Engelbrecht
1Toxicology Laboratory, Leiden University Medical Center, The Netherlands. b.leussink@lumc.nl
Archives of Toxicology
|April 18, 2001
Summary
High doses of colloidal bismuth subcitrate (CBS) can cause reversible kidney damage in rats, particularly affecting the proximal tubules. This study establishes a new model for bismuth-induced nephropathy.
Area of Science:
- Nephrology
- Toxicology
- Pharmacology
Background:
- Colloidal bismuth subcitrate (CBS) treats peptic ulcers and H. pylori infections.
- CBS overdose can cause human nephrotoxicity, but the renal damage mechanism and experimental models are poorly understood.
Purpose of the Study:
- To establish a rat model for bismuth-induced nephropathy.
- To investigate the nature of renal damage caused by CBS overdose.
Main Methods:
- Female Wistar rats received single oral doses of CBS (0.75, 1.5, or 3.0 mmol Bi/kg) or vehicle.
- Kidney function, urinary N-acetyl-beta-D-glucosaminidase (NAG), and bismuth levels were monitored for 14 days.
- Histological examination of kidney tissues was performed.
Main Results:
- A dose of 3.0 mmol Bi/kg induced acute kidney injury (proteinuria, glucosuria, elevated plasma urea/creatinine) within 6 hours.
- Renal function recovered within 10 days in most rats.
- Histology showed proximal tubule (S3 segment) necrosis, with S1/S2 segment involvement at higher bismuth absorption, and leukocyte infiltration.
Conclusions:
- A rat model for bismuth-induced reversible nephropathy was successfully developed.
- Large single oral CBS overdoses cause proximal tubule damage, primarily in the S3 segment.
- The damage is dose-dependent and reversible.