Studies on experimental renal damage in rats

  • FURUHAMA Kazuhisa
    Drug Safety Research Center, Research Institute, Daiichi Seiyaku Co., Ltd.
  • YAMADA Masao
    Drug Safety Research Center, Research Institute, Daiichi Seiyaku Co., Ltd.
  • ONODERA Takeshi
    Drug Safety Research Center, Research Institute, Daiichi Seiyaku Co., Ltd.

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Other Title
  • ラット実験的じん障害の臨床生化学的研究  III 血中PSP半減期とじん障害の関連性
  • ラット ジッケンテキ ジン ショウガイ ノ リンショウ セイカガクテキ ケンキ
  • 第3報 血中PSP半減期と腎障害の関連性

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The serum half-life of PSP(PSP t/2) was determined in normal and nephropathy rats by repeated blood collection under an unanesthetized condition to estimate its usefulness as a renal functional parameter. In normal rats, the serum disappearance curve of PSP (5 mg/kg) could be resolved into two exponential components, and the mean PSP t/2 in the second component was 12 min (n=100). About 71% of the PSP loaded was excreted in urine and 19% in bile. A single subcutaneous injection of HgC12 delayed the serum disappearance of PSP and simultaneously decreased its urinary excretion and increased its biliary excretion. The serum protein binding ratio of PSP became higher when the serum concentration of PSP was decreased, while it became lower when the serum albumin level was decreased. PSP t/2 in rats treated with gentamicin or puromycin amino-nucleoside as well as that in rats given HgCl2 was increased in correlation with changes in common renal functional parameters such as serum urea nitrogen, serum creatinine, urinary protein and morphologic changes of the kidney. Masugi-type nephritis rats showed no change in PSP t/2. Moreover, PSP t/2 was well correlated with the maximal tubular secretion rate of p-amino-hippuric acid. Since PSP t/2 can be determined periodically on the same animal, it is considered to have effective application as a renal functional test in rats, especially for examining tubular secretion.

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