Prevention of endotoxin-induced uveitis in rats by benfotiamine, a lipophilic analogue of vitamin B1

Umesh C S Yadav, Sumitra Subramanyam, Kota Ramana

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

PURPOSE. To study the amelioration of ocular inflammation in endotoxin-induced uveitis (EIU) in rats by benfotiamine, a lipid-soluble analogue of thiamine. METHODS. EIU in Lewis rats was induced by subcutaneous injection of lipopolysaccharide (LPS) followed by treatment with benfotiamine. The rats were killed 3 or 24 hours after LPS injection, eyes were enucleated, aqueous humor (AqH) was collected, and the number of infiltrating cells, protein concentration, and inflammatory marker levels were determined. Immunohistochemical analysis of eye sections was performed to determine the expression of inducible-nitric oxide synthase (iNOS), cyclooxygenase (Cox)-2, protein kinase C (PKC), and transcription factor NF-kB. RESULTS. Infiltrating leukocytes, protein concentrations, and inflammatory cytokines and chemokines were significantly elevated in the AqH of EIU rats compared with control rats, and benfotiamine treatment suppressed these increases. Similarly increased expression of inflammatory markers iNOS and Cox-2 in ciliary body and retinal wall was also significantly inhibited by benfotiamine. The increased phosphorylation of PKC and the activation of NF-kB in the ciliary body and in the retinal wall of EIU rat eyes were suppressed by benfotiamine. CONCLUSIONS. These results suggest that benfotiamine suppresses oxidative stress-induced NF-kB-dependent inflammatory signaling leading to uveitis. Therefore, benfotiamine could be used as a novel therapeutic agent for the treatment of ocular inflammation, especially uveitis.

Original languageEnglish (US)
Pages (from-to)2276-2282
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume50
Issue number5
DOIs
StatePublished - 2009

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Thiamine
Uveitis
Endotoxins
NF-kappa B
Ciliary Body
Aqueous Humor
Nitric Oxide Synthase Type II
Cyclooxygenase 2
Protein Kinase C
Lipopolysaccharides
Inflammation
Subcutaneous Injections
Therapeutics
benphothiamine
Chemokines
Proteins
Oxidative Stress
Leukocytes
Cell Count
Phosphorylation

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Prevention of endotoxin-induced uveitis in rats by benfotiamine, a lipophilic analogue of vitamin B1. / Yadav, Umesh C S; Subramanyam, Sumitra; Ramana, Kota.

In: Investigative Ophthalmology and Visual Science, Vol. 50, No. 5, 2009, p. 2276-2282.

Research output: Contribution to journalArticle

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N2 - PURPOSE. To study the amelioration of ocular inflammation in endotoxin-induced uveitis (EIU) in rats by benfotiamine, a lipid-soluble analogue of thiamine. METHODS. EIU in Lewis rats was induced by subcutaneous injection of lipopolysaccharide (LPS) followed by treatment with benfotiamine. The rats were killed 3 or 24 hours after LPS injection, eyes were enucleated, aqueous humor (AqH) was collected, and the number of infiltrating cells, protein concentration, and inflammatory marker levels were determined. Immunohistochemical analysis of eye sections was performed to determine the expression of inducible-nitric oxide synthase (iNOS), cyclooxygenase (Cox)-2, protein kinase C (PKC), and transcription factor NF-kB. RESULTS. Infiltrating leukocytes, protein concentrations, and inflammatory cytokines and chemokines were significantly elevated in the AqH of EIU rats compared with control rats, and benfotiamine treatment suppressed these increases. Similarly increased expression of inflammatory markers iNOS and Cox-2 in ciliary body and retinal wall was also significantly inhibited by benfotiamine. The increased phosphorylation of PKC and the activation of NF-kB in the ciliary body and in the retinal wall of EIU rat eyes were suppressed by benfotiamine. CONCLUSIONS. These results suggest that benfotiamine suppresses oxidative stress-induced NF-kB-dependent inflammatory signaling leading to uveitis. Therefore, benfotiamine could be used as a novel therapeutic agent for the treatment of ocular inflammation, especially uveitis.

AB - PURPOSE. To study the amelioration of ocular inflammation in endotoxin-induced uveitis (EIU) in rats by benfotiamine, a lipid-soluble analogue of thiamine. METHODS. EIU in Lewis rats was induced by subcutaneous injection of lipopolysaccharide (LPS) followed by treatment with benfotiamine. The rats were killed 3 or 24 hours after LPS injection, eyes were enucleated, aqueous humor (AqH) was collected, and the number of infiltrating cells, protein concentration, and inflammatory marker levels were determined. Immunohistochemical analysis of eye sections was performed to determine the expression of inducible-nitric oxide synthase (iNOS), cyclooxygenase (Cox)-2, protein kinase C (PKC), and transcription factor NF-kB. RESULTS. Infiltrating leukocytes, protein concentrations, and inflammatory cytokines and chemokines were significantly elevated in the AqH of EIU rats compared with control rats, and benfotiamine treatment suppressed these increases. Similarly increased expression of inflammatory markers iNOS and Cox-2 in ciliary body and retinal wall was also significantly inhibited by benfotiamine. The increased phosphorylation of PKC and the activation of NF-kB in the ciliary body and in the retinal wall of EIU rat eyes were suppressed by benfotiamine. CONCLUSIONS. These results suggest that benfotiamine suppresses oxidative stress-induced NF-kB-dependent inflammatory signaling leading to uveitis. Therefore, benfotiamine could be used as a novel therapeutic agent for the treatment of ocular inflammation, especially uveitis.

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