Pantethine Prevents Murine Systemic Sclerosis Through the Inhibition of Microparticle Shedding.

Abstract

OBJECTIVE:

Endothelial cell (EC) damage in systemic sclerosis (SSc) is reflected by the shedding of microparticles (MPs). The aim of this study was to show that inhibiting MP release using pantethine or by inactivating ATP-binding cassette transporter A1 (ABCA1) ameliorates murine SSc.

METHODS:

First, the effects of pantethine on MP shedding and on basal oxidative and nitrosative stresses in ECs and fibroblasts were determined in vitro. The effects of pantethine were then tested in vivo. SSc was induced in BALB/c mice by daily intradermal injection of HOCl. Mice were simultaneously treated daily with pantethine by oral gavage.

RESULTS:

In vitro, pantethine inhibited MP shedding from tumor necrosis factor-stimulated ECs and abrogated MP-induced oxidative and nitrosative stresses in ECs and fibroblasts. Ex vivo, pantethine also restored redox homeostasis in fibroblasts from mice with SSc. In vivo, mice with SSc displayed skin and lung fibrosis associated with increased levels of circulating MPs and markers of oxidative and endothelial stress, which were normalized by administration of pantethine or inactivation of ABCA1.

CONCLUSION:

Pantethine is a well-tolerated molecule that represents a potential treatment of human SSc.

• Authors: Niloufar Kavian, Wioleta Marut, Amélie Servettaz, Carole Nicco, Christiane Chéreau, Hervé Lemaréchal, Philippe Guilpain, Giovanna Chimini, Franck Galland, Bernard Weill, Philippe Naquet, Frédéric Batteux
• Journal: Arthritis & rheumatology (Hoboken, N.J.) (Arthritis Rheumatol) Vol. 67 Issue 7 Pg. 1881-90 (Jul 2015) ISSN: 2326-5205 [Electronic] United States
• PMID: 25776044 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015, American College of Rheumatology.

Chemical References

• ABCA1 protein, mouse
• ATP Binding Cassette Transporter 1
• Bleomycin
• Pantetheine
• Hypochlorous Acid
• pantethine

Topics

• ATP Binding Cassette Transporter 1 (deficiency, genetics, metabolism)
• Administration, Oral
• Animals
• Bleomycin (administration & dosage, adverse effects)
• Cell-Derived Microparticles (drug effects, pathology)
• Cells, Cultured
• Disease Models, Animal
• Endothelial Cells (drug effects, metabolism, pathology)
• Female
• Fibroblasts (drug effects, metabolism, pathology)
• Homeostasis (drug effects)
• Hypochlorous Acid (administration & dosage, adverse effects)
• In Vitro Techniques
• Injections, Intradermal
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Oxidative Stress (drug effects)
• Pantetheine (administration & dosage, analogs & derivatives, pharmacology, therapeutic use)
• Scleroderma, Systemic (chemically induced, pathology, prevention & control)
• Treatment Outcome