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Nephrotoxic effect of Tris(2,3‐dibromopropyl) phosphate on rat urinary metabolites: Assessment from 13 C‐NMR spectra of urines and biochemical and histopathological examinations
Author(s) -
Fukuoka Masamichi,
Takahashi Terue,
Tanaka Akira,
Yamaha Tsutomu,
Naito Katushi,
Nakaji Yukio,
Kobayashi Kazuo,
Tobe Masuo
Publication year - 1987
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2550070106
Subject(s) - tris , metabolite , chemistry , nephrotoxicity , lactate dehydrogenase , alkaline phosphatase , endocrinology , excretion , urinary system , kidney , medicine , acute tubular necrosis , urine , biochemistry , renal function , enzyme , biology
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 13 C‐NMR and biochemical examinations. Tris‐BP produced significant increases of urinary glucose and lactate. Urinary γ‐glutamyitransferase, 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 13 C‐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.