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 K. Srivastava, Kota V. Ramana

Research output: Contribution to journalArticle

28 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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