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Comparative studies on nephrotoxic effects of Tris (2,3‐dibromopropyl) phosphate and Bis (2,3‐dibromopropyl) phosphate on rat urinary metabolites
Author(s) -
Fukuoka Masamichi,
Takahashi Terue,
Naito Katsushi,
Takada Koichi
Publication year - 1988
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.2550080108
Subject(s) - tris , chemistry , excretion , urine , endocrinology , lactate dehydrogenase , medicine , urinary system , uric acid , metabolite , alkaline phosphatase , biochemistry , enzyme , biology
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 μmol/kg tris (2,3‐dibromopropyl) phosphate (Tris‐BP) or bis (2,3‐dibromopropyl) phosphate (Bis‐BP). Urine was collected over a 24 h period and subjected to biochemical examinations. Comparative studies on Tris‐BP‐ and Bis‐BP‐induced nephrotoxicities were carried out for abnormal patterns of urinary excretion. The urinary excretion of glucose was higher in Bis‐BP than Tris‐BP at a dose of 143.4 μmol/kg, but this pattern reversed at a dose of 286.8 μmol/kg. Peak lactate excretion occurred later than peak glucose excretion with 143.4 and 286.8 μmol/kg Tris BP and 143.4 μmol/kg Bis‐BP. Bis‐BP 286.8 μmol/kg caused a transient urinary elevation of lactate on Day 2. Uric acid was excreted at higher levels for Bis‐BP than Tris‐BP on day 2 of urine collection. Activities of urinary enzymes including alkaline phosphatase, aspartate aminotransferase and γ‐glutamyltransferase, were different on the first day of post‐treatment for Tris‐BP and Bis‐BP. Leucine aminopeptidase and lactate dehydrogenase levels differed on the second day. Activities of the former enzymes on the day 2 urine suggested a transformation of Tris‐BP to Bis‐BP. Urinary patterns of lactate dehydrogenase isoenzymes (LDH‐1‐LDH‐5) were different between Tris‐BP and Bis‐BP when rats were treated with the dose of 286.8 μmol/kg: Tris‐BP caused a higher excretion of LDH‐4 and LDH‐5 in urine on day 1 and all five isoenzymes into the day 2 urine. Bis‐BP caused slightly higher excretion of LDH‐5 and LDH‐4 into the day 1 and 3 urine, respectively. Bis‐BP but not Tris‐BP caused abnormally urinary excretion of sodium ion. Histopathologically, the nephrotoxic effect of Tris‐BP appeared one day later and was more obvious than that of Bis‐BP in rats after single oral administration.