Effective Nephroprotection Against Acute Kidney Injury with a Star-Shaped Polyglutamate-Curcuminoid Conjugate

Autores de CIPF

• Aroa Duro Castaño

  Autor

• 

  Maria Jesus Vicent Docon

  Autor

Participantes ajenos a CIPF

• Cordoba-David, G
• Castelo-Branco, RC
• Gonzalez-Guerrero, C
• Cannata, P
• Sanz, AB
• Ortiz, A
• Ramos, AM

Grupos de Investigación

• Laboratorio de Polímeros Terapéuticos

  

  Jefe/a de Grupo

  Maria Jesus Vicent Docon

Abstract

The lack of effective pharmacological treatments for acute kidney injury (AKI) remains a significant 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 (St-PGA-CL-BDMC) inhibits apoptosis and necroptosis induced by Tweak/TNF alpha /IFN gamma alone or concomitant to caspase inhibition. St-PGA-CL-BDMC also reduced NF-kappa B 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 inflammation, while preserving the kidney expression of the protective factor, Klotho. Thus, due to renal accumulation and attractive pharmacological properties, the application of PGA-based therapeutics may improve nephroprotective properties of current AKI treatments.