OBJECTIVE: Alkaptonuria (AKU) is an ultra-rare autosomal recessive disease that currently lacks an appropriate therapy. Recently we provided experimental evidence that AKU is a secondary serum amyloid A (SAA)-based amyloidosis. The aim of the present work was to evaluate the use of antioxidants to inhibit SAA amyloid and pro-inflammatory cytokine release in AKU. METHODS: We adopted a human chondrocytic cell AKU model to evaluate the anti-amyloid capacity of a set of antioxidants that had previously been shown to counteract ochronosis in a serum AKU model. Amyloid presence was evaluated by Congo red staining. Homogentisic acid-induced SAA production and pro-inflammatory cytokine release (overexpressed in AKU patients) were evaluated by ELISA and multiplex systems, respectively. Lipid peroxidation was evaluated by means of a fluorescence-based assay. RESULTS: Our AKU model allowed us to prove the efficacy of ascorbic acid combined with N-acetylcysteine, taurine, phytic acid and lipoic acid in significantly inhibiting SAA production, pro-inflammatory cytokine release and membrane lipid peroxidation. CONCLUSION: All the tested antioxidant compounds were able to reduce the production of amyloid and may be the basis for establishing new therapies for AKU amyloidosis.

Spreafico, A., Millucci, L., Ghezzi, L., Geminiani, M., Braconi, D., Amato, L., et al. (2013). Antioxidants inhibit SAA formation and pro-inflammatory cytokine release in a human cell model of alkaptonuria. RHEUMATOLOGY, 52((9)), 1667-1673 [10.1093/rheumatology/ket185].

Antioxidants inhibit SAA formation and pro-inflammatory cytokine release in a human cell model of alkaptonuria.

SPREAFICO, ADRIANO;MILLUCCI, LIA;GHEZZI, LORENZO;GEMINIANI, MICHELA;BRACONI, DANIELA;AMATO, LOREDANA;CHELLINI, FEDERICO;FREDIANI, BRUNO;MORETTI, ELENA;COLLODEL, GIULIA;BERNARDINI, GIULIA;SANTUCCI, ANNALISA
2013-01-01

Abstract

OBJECTIVE: Alkaptonuria (AKU) is an ultra-rare autosomal recessive disease that currently lacks an appropriate therapy. Recently we provided experimental evidence that AKU is a secondary serum amyloid A (SAA)-based amyloidosis. The aim of the present work was to evaluate the use of antioxidants to inhibit SAA amyloid and pro-inflammatory cytokine release in AKU. METHODS: We adopted a human chondrocytic cell AKU model to evaluate the anti-amyloid capacity of a set of antioxidants that had previously been shown to counteract ochronosis in a serum AKU model. Amyloid presence was evaluated by Congo red staining. Homogentisic acid-induced SAA production and pro-inflammatory cytokine release (overexpressed in AKU patients) were evaluated by ELISA and multiplex systems, respectively. Lipid peroxidation was evaluated by means of a fluorescence-based assay. RESULTS: Our AKU model allowed us to prove the efficacy of ascorbic acid combined with N-acetylcysteine, taurine, phytic acid and lipoic acid in significantly inhibiting SAA production, pro-inflammatory cytokine release and membrane lipid peroxidation. CONCLUSION: All the tested antioxidant compounds were able to reduce the production of amyloid and may be the basis for establishing new therapies for AKU amyloidosis.
Spreafico, A., Millucci, L., Ghezzi, L., Geminiani, M., Braconi, D., Amato, L., et al. (2013). Antioxidants inhibit SAA formation and pro-inflammatory cytokine release in a human cell model of alkaptonuria. RHEUMATOLOGY, 52((9)), 1667-1673 [10.1093/rheumatology/ket185].
File in questo prodotto:
File Dimensione Formato  
Millucci et al RHEUMATOLOGY 2013.pdf

non disponibili

Tipologia: Post-print
Licenza: PUBBLICO - Pubblico con Copyright
Dimensione 670.6 kB
Formato Adobe PDF
670.6 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/45901
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo