The mechanism of Tris-BP or Bis-BP (a metabolite of Tris-BP) induced nephrotoxicity was investigated by determining urinary excretion of enzymes and selected metabolites. Rats received single oral doses of 0, 71.7, 143.4 and 286.8 mumol/kg tris (2,3-dibromopropyl) phosphate (Tris-BP) or bis (2,3-dib
Nephrotoxic effect of Tris(2,3-dibromopropyl) phosphate on rat urinary metabolites: Assessment from 13C-NMR spectra of urines and biochemical and histopathological examinations
โ Scribed by Masamichi Fukuoka; Terue Takahashi; Akira Tanaka; Tsutomu Yamaha; Katushi Naito; Yukio Nakaji; Kazuo Kobayashi; Masuo Tobe
- Publisher
- John Wiley and Sons
- Year
- 1987
- Tongue
- English
- Weight
- 992 KB
- Volume
- 7
- Category
- Article
- ISSN
- 0260-437X
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โฆ Synopsis
Rats received either single oral doses of 0, 25, 50, 100 and 200 mg/kg tris(2,3-dibromopropyl)phosphate (Tris-BP) or repeated doses of 50, 100 and 200 mg/kg/day Tris-BP for 7 days. Urine was collected over a 24-hr period and subjected to ' C N M R and biochemical examinations. Tris-BP produced significant increases of urinary glucose and lactate. Urinary y-glutamyltransferase, lactate dehydrogenase and alkaline phosphatase levels were significantly elevated on the first 2 days of post-treatment. Histopathologically, the kidney exhibited proximal tubular damage at a dose of 200 mg/kg. There was a good correlation among the histopathological, biochemical results, and the I3C-NMR urinary metabolite fingerprints in the assessment of Tris-BP-induced renal damage. The abnormal patterns of metabolite excretion suggested that the lesions produced by Tris-BP were caused by changes in the metabolic function of tubular epithelial cells. The urinary excretion of lactate, enzymes and inhibition of glucose reabsorption from the tubular lumina may be attributed to necrosis and desquamation of the tubular cell.
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