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

Umesh C S Yadav, Nilesh M. Kalariya, Satish Srivastava, Kota Ramana

Research output: Contribution to journalArticle

26 Citations (Scopus)

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 κB and consequent activation and nuclear translocation of the redox-sensitive transcription factor NF-κB 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 PGE2 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-κB activation and prevents bacterial endotoxin-induced inflammation, indicating that vitamin B1 supplementation could be beneficial in the treatment of inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)1423-1434
Number of pages12
JournalFree Radical Biology and Medicine
Volume48
Issue number10
DOIs
StatePublished - May 2010

Fingerprint

Macrophages
Thiamine
Lipopolysaccharides
Fats
Chemical activation
Phosphorylation
MAP Kinase Kinase 4
Apoptosis Inducing Factor
Inflammation
Oxidative stress
Mitochondrial Membrane Potential
Phospholipases A2
p38 Mitogen-Activated Protein Kinases
Cytotoxicity
Cytochromes c
Chemokines
Dinoprostone
Endotoxins
Caspase 3
Protein Kinase C

Keywords

  • Benfotiamine
  • Free radicals
  • Inflammation
  • Macrophages
  • NF-κB
  • Oxidative stress
  • Vitamin B1

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Protective role of benfotiamine, a fat-soluble vitamin B1 analogue, in lipopolysaccharide-induced cytotoxic signals in murine macrophages. / Yadav, Umesh C S; Kalariya, Nilesh M.; Srivastava, Satish; Ramana, Kota.

In: Free Radical Biology and Medicine, Vol. 48, No. 10, 05.2010, p. 1423-1434.

Research output: Contribution to journalArticle

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