Bismuth biokinetics and kidney histopathology after bismuth overdose in rats.
Bismuth induced nephrotoxicity has been reported to occur after acute overdoses of Bi-containing therapeutic drugs. We studied the development of bismuth induced nephropathy and bismuth biokinetics in rats. Bismuth nephropathy was induced in 33 young adult female Wistar rats weighing ca. 175 g by feeding them a single overdose of colloidal bismuth subcitrate containing 3.0 mmol Bi/kg at (t = 0). Control animals (n = 7) were fed the vehicle only. The animals were sacrificed after 1-48 h. Plasma creatinine increased from 51 +/- 6 micromol/l at t = 0 to 550 +/- 250 micromol/l after 48 h in the experimental group. The S3 segment of the proximal tubule showed epithelial cell vacuolation after 1 h and necrosis after 3 h. Cells of the S1/S2 segment demonstrated vacuolation after 6 h and necrosis after 12 h. Biokinetics of bismuth in blood could best be described with a one-compartment model characterized by an absorption half-life of 0.32 h and an elimination halflife of 16 h. The peak concentration of about 7.0 mg Bi/l was reached after 2 h. In conclusion, cells of the S3 segment of the proximal tubule necrotized first after an oral colloidal bismuth subcitrate overdose and biokinetics of Bi in blood was best described by a one-compartment model.
Leussink
B T
BT
Toxicology Laboratory, Leiden University Medical Center, The Netherlands. B.LEUSSINK@LUMC.NL
Slikkerveer
A
A
Krauwinkel
W J
WJ
van der Voet
G B
GB
de Heer
E
E
de Wolff
F A
FA
Bruijn
J A
JA
D000042:Absorption; D000818:Animals; D000897:Anti-Ulcer Agents / Q000633:toxicity*; D001729:Bismuth / Q000493:pharmacokinetics*; D001786:Blood Glucose / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D006207:Half-Life; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009336:Necrosis; D009942:Organometallic Compounds / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D023382:Toxicity Tests, Acute; D014617:Vacuoles / Q000187:drug effects / Q000473:pathology
D000897:Anti-Ulcer Agents; D001786:Blood Glucose; D009942:Organometallic Compounds; D003404:Creatinine; C002791:bismuth tripotassium dicitrate; D001729:Bismuth