5-Aminolevulinic Acid Protects against Cisplatin-Induced Nephrotoxicity without Compromising the Anticancer Efficiency of Cisplatin in Rats In Vitro and In Vivo
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- Jeff M. Sands
- editor
書誌事項
- 公開日
- 2013-12-06
- 資源種別
- journal article
- 権利情報
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- http://creativecommons.org/licenses/by/3.0/
- DOI
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- 10.1371/journal.pone.0080850
- 公開者
- Public Library of Science (PLoS)
説明
Nephrotoxicity is a frequent and major limitation in cisplatin (CDDP)-based chemotherapy. 5-Aminolevulinic acid (ALA) is widely distributed in animal cells, and it is a precursor of tetrapyrole compounds such as heme that is fundamentally important in aerobic energy metabolism. The aim of this study is to evaluate the protective role of ALA in CDDP-induced acute kidney injury (AKI).We used CDDP-induced AKI rat model and cultured renal tubular cells (NRK-52E). We divided four groups of rats: control, CDDP only, CDDP + ALA(post);(ALA 10 mg/kg + Fe in drinking water) after CDDP, CDDP + ALA(prepost).CDDP increased Cr up to 6.5 mg/dl, BUN up to 230 mg/dl, and ALA significantly reduced these changes. ALA ameliorates CDDP-induced morphological renal damages, and reduced tubular apoptosis evaluated by TUNEL staining and cleaved caspase 3. Protein and mRNA levels of ATP5α, complex(COX) IV, UCP2, PGC-1α in renal tissue were significantly decreased by CDDP, and ALA ameliorates reduction of these enzymes. In contrast, Heme Oxigenase (HO)-1 level is induced by CDDP treatment, and ALA treatment further up-regulates HO-1 levels. In NRK-52E cells, the CDDP-induced reduction of protein and mRNA levels of mitochondrial enzymes was significantly recovered by ALA + Fe. CDDP-induced apoptosis were ameliorated by ALA + Fe treatment. Furthermore, we evaluated the size of transplantated bladder carcinoma to the rat skin, and ALA did not change the anti cancer effects of CDDP.These data suggested that the protective role of ALA in cisplatin-induced AKI is via protection of mitochondrial viability and prevents tubular apoptosis. Also there are no significant effects of ALA on anticancer efficiency of CDDP in rats. Thus, ALA has the potential to prevent CDDP nephrotoxicity without compromising its anticancer efficacy.
収録刊行物
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- PLoS ONE
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PLoS ONE 8 (12), e80850-, 2013-12-06
Public Library of Science (PLoS)
- Tweet
キーワード
- Male
- Science
- Iron
- Gene Expression
- Antineoplastic Agents
- Apoptosis
- Protective Agents
- Ion Channels
- Cell Line
- Electron Transport Complex IV
- Mitochondrial Proteins
- Rats, Sprague-Dawley
- Tissue Culture Techniques
- Animals
- Uncoupling Protein 2
- Skin
- Caspase 3
- Q
- Carcinoma
- R
- Aminolevulinic Acid
- Acute Kidney Injury
- Mitochondrial Proton-Translocating ATPases
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
- Rats
- Tumor Burden
- Kidney Tubules
- Oxidative Phosphorylation Coupling Factors
- Urinary Bladder Neoplasms
- Medicine
- Cisplatin
- Heme Oxygenase-1
- Neoplasm Transplantation
- Research Article
- Transcription Factors
詳細情報 詳細情報について
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- CRID
- 1360848662465055872
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- ISSN
- 19326203
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- PubMed
- 24324635
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- 資料種別
- journal article
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- データソース種別
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- Crossref
- KAKEN
- OpenAIRE