| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Outline of Final Research Achievements |
Nephrotoxicity induced by anti-microorganism or anti-cancer drugs is a serious clinical problem. Megalin, an endocytic receptor expressed at the proximal tubules, may mediates the nephrotoxicity of these drugs. The mechanisms underlying the nephrotoxicity are unknown. In this study, using quartz-crystal microbalance analysis, we found that megalin is bound by colistin, vancomycin and cisplatin, and the binding of these drugs to megalin is competed with cilastatin. Using mosaic megalin knockout mice, we revealed that the nephrotoxicity induced by colistin, vancomycin, and cisplatin depends on megalin expression. We showed that colistin-induced nephrotoxicity is suppressed by concomitant cilastatin administration. We also found that cilastatin does not inhibit the anti-bacterial activity of gentamicin, colistin, and vancomycin in vitro. In conclusion, megalin blockade with cilastatin suppresses efficiently the nephrotoxicity induced by gentamicin, colistin, vancomycin, and cisplatin.
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