Involvement of Indoxyl Sulfate in Renal and Central Nervous System Toxicities During Cisplatin-induced Acute Renal Failure
In: Pharmaceutical Research, Jg. 24 (2007-02-21), S. 662-671
Online
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Zugriff:
The purpose of the present study was to explore the involvement of indoxyl sulfate (IS) in nephrotoxicity and central nervous system (CNS) toxicity in cisplatin (CDDP)-treated rats. Renal function was evaluated by serum creatinine and BUN levels. The IS levels in the serum, brain and kidney was monitored by high-performance liquid chromatography method. Body weight and rectal temperature were monitored. Real-time PCR analysis was performed to examine rPer2 mRNA expression. Renal function deteriorated in a time-dependent manner after administration of CDDP. The concentration of IS in the serum, brain and kidney markedly increased 24–84 h after commencement of CDDP treatment. The observed increase in the levels of serum creatinine, BUN and IS was suppressed by concomitant administration of AST-120. Rectal temperature was significantly lowered 72–92 h after CDDP-treatment, which was partially restored by coadministration of AST-120. Moreover, the amplitude of rectal temperature rhythms was disrupted by treatment with CDDP. Circadian rhythm of rPer2 mRNA expression, a clock gene, in suprachiasmatic nucleus (SCN) and kidney was disturbed in CDDP-treated rats. An increase in the IS level and the associated disturbance to the circadian rhythm are involved in the renal and CNS toxicities in CDDP-treatment.
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Involvement of Indoxyl Sulfate in Renal and Central Nervous System Toxicities During Cisplatin-induced Acute Renal Failure
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Autor/in / Beteiligte Person: | Hamada, Akinobu ; Morisaki, Takafumi ; Iwata, Kazufumi ; Saito, Hideyuki ; Matsuzaki, Takanobu ; Ohmura, Takafumi ; Watanabe, Hiroshi |
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Zeitschrift: | Pharmaceutical Research, Jg. 24 (2007-02-21), S. 662-671 |
Veröffentlichung: | Springer Science and Business Media LLC, 2007 |
Medientyp: | unknown |
ISSN: | 1573-904X (print) ; 0724-8741 (print) |
DOI: | 10.1007/s11095-006-9183-2 |
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