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

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.

• Authors: Adriano Spreafico, Lia Millucci, Lorenzo Ghezzi, Michela Geminiani, Daniela Braconi, Loredana Amato, Federico Chellini, Bruno Frediani, Elena Moretti, Giulia Collodel, Giulia Bernardini, Annalisa Santucci
• Journal: Rheumatology (Oxford, England) (Rheumatology (Oxford)) Vol. 52 Issue 9 Pg. 1667-73 (Sep 2013) ISSN: 1462-0332 [Electronic] England
• PMID: 23704321 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Cytokines
• Serum Amyloid A Protein
• Taurine
• Thioctic Acid
• Phytic Acid
• Ascorbic Acid
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Alkaptonuria (metabolism)
• Antioxidants (pharmacology)
• Ascorbic Acid (pharmacology)
• Cell Line
• Chondrocytes (drug effects, metabolism)
• Cytokines (metabolism)
• Humans
• Inflammation (metabolism)
• Lipid Peroxidation (drug effects, physiology)
• Phytic Acid (pharmacology)
• Serum Amyloid A Protein (metabolism)
• Taurine (pharmacology)
• Thioctic Acid (pharmacology)