Effective nephroprotection against acute kidney injury with a star-shaped polyglutamate-curcuminoid conjugate
Entity
UAM. Departamento de MedicinaPublisher
Nature ResearchDate
2020-02-06Citation
10.1038/s41598-020-58974-9
Scientific Reports 10 (2020): 2056
ISSN
2045-2322DOI
10.1038/s41598-020-58974-9Funded by
Tis work was supported by grants from the Instituto de Salud Carlos III, FEDER funds: PI16/02057, PI16/01900, PI18/01133, PI19/00815, ISCIII RETIC REDINREN RD16/0009; Sociedad Española de Nefrología; FRIAT; Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM; ERA-PerMed-JTC2018 (AC18/00071; DTS18/00032); Spanish Ministry of Economy and Competitiveness (Grant numbers SAF2013-44848-R, SAF2016-80427-R). Partly co-funded by FEDER (PO FEDER Valencian Community - 2014–2020)Project
Gobierno de España. PI16/02057; Gobierno de España. PI16/01900; Gobierno de España. PI18/01133; Gobierno de España. PI19/00815; Gobierno de España. RD16/0009; Comunidad de Madrid. B2017/BMD-3686/CIFRA2-CM; Gobierno de España. AC18/00071; Gobierno de España. DTS18/00032; Gobierno de España. SAF2013-44848-R; Gobierno de España. SAF2016-80427-REditor's Version
https://doi.org/10.1038/s41598-020-58974-9Subjects
acute kidney injury (AKI); curcuminoids; AKI treatment; MedicinaRights
© 2020 The AuthorsAbstract
The lack of efective pharmacological treatments for acute kidney injury (AKI) remains a signifcant
public health problem. Given the involvement of apoptosis and regulated necrosis in the initiation
and progression of AKI, the inhibition of cell death may contribute to AKI prevention/recovery.
Curcuminoids are a family of plant polyphenols that exhibit attractive biological properties that make
them potentially suitable for AKI treatment. Now, in cultured tubular cells, we demonstrated that a
crosslinked self-assembled star-shaped polyglutamate (PGA) conjugate of bisdemethoxycurcumin (StPGA-CL-BDMC) inhibits apoptosis and necroptosis induced by Tweak/TNFα/IFNγ alone or concomitant
to caspase inhibition. St-PGA-CL-BDMC also reduced NF-κB activation and subsequent gene
transcription. In vivo, St-PGA-CL-BDMC prevented renal cell loss and preserved renal function in mice
with folic acid-induced AKI. Mechanistically, St-PGA-CL-BDMC inhibited AKI-induced apoptosis and
expression of ferroptosis markers and also decreased the kidney expression of genes involved in tubular
damage and infammation, while preserving the kidney expression of the protective factor, Klotho.
Thus, due to renal accumulation and attractive pharmacological properties, the application of PGAbased therapeutics may improve nephroprotective properties of current AKI treatments
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Google Scholar:Córdoba-David, Gina
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Duro-Castano, Aroa
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Cardoso Castelo-Branco, Regiane
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González-Guerrero, Cristian
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Cannata, Pablo
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Sanz, Ana B.
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Vicent, María J.
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Ortiz Arduán, Alberto
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Ramos, Adrián M.
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