Protective Effect of Serum Thymic Factor, FTS, on Cephaloridine-Induced Nephrotoxicity in Rats(Pharmacology)
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概要
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Serum thymic factor (FTS), a thymic peptide hormone, has been reported to increase superoxide disumutase (SOD) levels in senescence-accelerated mice. In the present study, we examined the effect of FTS on cephaloridine (CER)-induced nephrotoxicity in vivo and in vitro. We previously reported that CER led to extracellular signal-regulated protein kinase (ERK) activation in the rat kidney. So, we also investigated whether FTS has an effect on ERK activation induced by CER. Treatment of male Sprague-Dawley rats with intravenous CER (1.2g/kg) for 24h markedly increased BUN and plasma creatinine levels and urinary excretion of glucose and protein, decreased creatinine clearance and also led to marked pathological changes in the proximal tubules, as revealed by electron micrographs. An increase in phosphorylated ERK (pERK) was detected in the nuclear fraction prepared from the rat kidney cortex 24h after CER injection. Pretreatment of rats with FTS (50μg/kg, i.v.) attenuated the CER-induced renal dysfunction and pathological damage. FTS also suppressed CER-induced ERK activation in the kidney. In vitro treatment of the established cell line, LLC-PK_1 cells, with FTS significantly ameliorated CER-induced cell injury, as measured by lactate dehydrogenase (LDH) leakage. Our results, taken together with our previous report that MEK inhibitors ameliorated CER-induced renal cell injury and ERK activation induced by CER, suggest that FTS participates in protection from CER-induced nephrotoxicity by suppressing ERK activation induced by CER.
- 2005-11-01
著者
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Awaya Akira
Science And Technology Corporation
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Awaya Akira
Japan Science And Technology Corporation
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Kohda Yuka
Laboratory Of Pharmacology Osaka University Of Pharmaceutical Sciences
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KOHDA Yuka
Division of Pharmacology, Osaka University of Pharmaceutical Sciences
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MATSUNAGA Yoshiko
Division of Pharmacology, Osaka University of Pharmaceutical Sciences
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YONOGI Katsuya
Division of Pharmacology, Osaka University of Pharmaceutical Sciences
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KAWAI Yoshiko
Division of Pharmacology, Osaka University of Pharmaceutical Sciences
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GEMBA Munekazu
Division of Pharmacology, Osaka University of Pharmaceutical Sciences
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Yonogi Katsuya
Division Of Pharmacology Osaka University Of Pharmaceutical Sciences
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Kawai Yoshiko
Laboratory Of Pharmacology Osaka University Of Pharmaceutical Sciences
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Kohda Yuka
Division Of Pharmacology Osaka University Of Pharmaceutical Sciences
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Awaya Akira
Japan Science And Technology Agency
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Kawai Yoshiko
Division Of Pharmacology Osaka University Of Farmaceutical Sciences
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Gemba Munekazu
Laboratory Of Functional Morphology Yokohama College Of Pharmacy
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Gemba M
Osaka Univ. Pharmaceutical Sci. Osaka Jpn
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Gemba Munekazu
Division Of Pharmacology Osaka University Of Pharmaceutical Sciences
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Gemba Munekazu
Division Of Pharmacology Osaka University Of Farmaceutical Sciences
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Matsunaga Yoshiko
Division Of Pharmacology Osaka University Of Pharmaceutical Sciences
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AWAYA Akira
Japan Science and Technology
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