Protective role of benfotiamine, a fat-soluble vitamin B1 analogue, in lipopolysaccharide-induced cytotoxic signals in murine macrophages.

Abstract

This study was designed to investigate the molecular mechanisms by which benfotiamine, a lipid-soluble analogue of vitamin B1, affects lipopolysaccharide (LPS)-induced inflammatory signals leading to cytotoxicity in the mouse macrophage cell line RAW264.7. Benfotiamine prevented LPS-induced apoptosis, expression of the Bcl-2 family of proapoptotic proteins, caspase-3 activation, and PARP cleavage and altered mitochondrial membrane potential and release of cytochrome c and apoptosis-inducing factor and phosphorylation and subsequent activation of p38-MAPK, stress-activated kinases (SAPK/JNK), protein kinase C, and cytoplasmic phospholipase A2 in RAW cells. Further, phosphorylation and degradation of inhibitory kappaB and consequent activation and nuclear translocation of the redox-sensitive transcription factor NF-kappaB were significantly prevented by benfotiamine. The LPS-induced increased expression of cytokines and chemokines and the inflammatory marker proteins iNOS and COX-2 and their metabolic products NO and PGE(2) was also blocked significantly. Thus, our results elucidate the molecular mechanism of the anti-inflammatory action of benfotiamine in LPS-induced inflammation in murine macrophages. Benfotiamine suppresses oxidative stress-induced NF-kappaB activation and prevents bacterial endotoxin-induced inflammation, indicating that vitamin B1 supplementation could be beneficial in the treatment of inflammatory diseases.

• Authors: Umesh C S Yadav, Nilesh M Kalariya, Satish K Srivastava, Kota V Ramana
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 48 Issue 10 Pg. 1423-34 (May 15 2010) ISSN: 1873-4596 [Electronic] United States
• PMID: 20219672 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• Apoptosis Inducing Factor
• Lipopolysaccharides
• Proto-Oncogene Proteins c-bcl-2
• Cytochromes c
• Parp1 protein, mouse
• Poly (ADP-Ribose) Polymerase-1
• Poly(ADP-ribose) Polymerases
• Caspase 3
• Thiamine
• benphothiamine

Topics

• Animals
• Apoptosis (drug effects)
• Apoptosis Inducing Factor (biosynthesis, genetics, metabolism)
• Caspase 3 (genetics, metabolism)
• Cell Line
• Cytochromes c (biosynthesis, genetics, metabolism)
• Cytoprotection
• Cytotoxicity, Immunologic (drug effects)
• Enzyme Activation (drug effects)
• Lipopolysaccharides (immunology, metabolism)
• Macrophage Activation (drug effects)
• Macrophages (drug effects, metabolism, pathology)
• Membrane Potential, Mitochondrial (drug effects)
• Mice
• Poly (ADP-Ribose) Polymerase-1
• Poly(ADP-ribose) Polymerases (genetics, metabolism)
• Proto-Oncogene Proteins c-bcl-2 (biosynthesis, genetics)
• Thiamine (analogs & derivatives, pharmacology)