Mechanism of urinary tract crystal formation following biphenyl treatment.
Coadministration of biphenyl and KHCO3 in the diet of male rats for 13 weeks produced urine crystals, which, by means of LC-MS/MS analyses, were determined to be composed of the potassium salt of 4-hydroxy-biphenyl-O-sulfate (4-HBPOSK). Biphenyl alone or biphenyl with KCl or NaHCO3 in the diet did not produce urine crystals. It was found that the higher concentration of potassium in the urine and the alkaline pH induced by feeding KHCO3 to rats resulted in the formation of urine crystals of 4-HBPOSK due to 4-HBPOSK solubility being lower in urine than in plasma. Urine crystals of 4-HBPOSK produced hyperplasia of the transitional epithelium of the ureter, ureteral obstruction, and hydronephrosis in the urinary tract.
Ohnishi
M
M
Japan Bioassay Research Center, Japan Industrial Safety and Health Association, Hadano-shi, Kanagawa, 257-0015, Japan. monishi@jisha.or.jp
Yajima
H
H
Takeuchi
T
T
Saito
M
M
Yamazaki
K
K
Kasai
T
T
Nagano
K
K
Yamamoto
S
S
Matsushima
T
T
Ishii
T
T
D000818:Animals; D001713:Biphenyl Compounds / Q000097:blood / Q000378:metabolism / Q000494:pharmacology* / Q000652:urine; D003460:Crystallization; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012995:Solubility; D014513:Ureter / Q000187:drug effects / Q000378:metabolism; D014551:Urinary Tract / Q000187:drug effects* / Q000378:metabolism; D014556:Urine / Q000737:chemistry
D001713:Biphenyl Compounds; C039430:4-hydroxybiphenyl-O-sulfonic acid; C010574:biphenyl; C004369:2-phenylphenol