Mechanisms Underlying Renal Tubular Acidosis and Albuminuria Induced by Cisplatin.
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Accession number;00A0997686
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| Title;Mechanisms Underlying Renal Tubular Acidosis and Albuminuria Induced by Cisplatin. |
| Author;
TAKANO MIKIHISA
(Hiroshima Univ., Sch. of Med.)
NAGAI JUN'YA
(Hiroshima Univ., Sch. of Med.)
SASAKI YUKI
(Hiroshima Univ., Sch. of Med.)
NAKANISHI NAOKI
(Hiroshima Univ., Sch. of Med.)
KITAHARA YASUMI
(Hiroshima Univ., Sch. of Med.)
MURAKAMI TERUO
(Hiroshima Univ., Sch. of Med.)
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Journal Title;Xenobiotic Metabolism and Disposition
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Journal Code:X0758A
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ISSN:0916-1139
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VOL.15;NO.Supplement;PAGE.S124-S125(2000)
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| Figure&Table&Reference;FIG.1, REF.1 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;The mechanisms underlying nephrotoxicity, specifically proximal tubular acidosis and albuminuria, induced by cisplatin(CDDP) were investigated. In the kidney, Na+/H+ exchanger and vacuolar(V)-H+-ATPase are two major H+ excretion systems located in the brush-border membrane. In brush-border membrane vesicles isolated from CDDP-teated rats, the activity of V-H+-ATPase, but not Na+/H+ exchanger, decreased markedly. In OK cells, CDDP treatment induced intracellular acidification. Thus, the inhibition of V-H+-ATPase would be involved in the proximal tubular acidosis induced by CDDP. V-H+-ATPase, as well as chloride channel ClC-5, in the endosomal membrane is important for the endocytic system. In OK cells, endocytosis of albumin was inhibited by CDDP, as well as by inhibitors for V-H+-ATPase and ClC-5. In vivo, CDDP administration to rats induced albuminuria, with maximum effect observed at 2-3 days after administration. Such a pattern was comparable with the inhibition of CDDP on V-H+-ATPase. Similar pattern was also observed for the urinary excretion of vitamin D binding protein, which is specifically taken up by the proximal tubular cells via megalin-mediated endocytosis. Taken together, the inhibition of V-H+-ATPase by CDDP would result in not only proximal tubular acidosis but also albuminuria(proteinuria). (author abst.) |
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