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


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-kappaB 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-kappaB-dependent inflammatory signaling leading to uveitis. Therefore, benfotiamine could be used as a novel therapeutic agent for the treatment of ocular inflammation, especially uveitis.
Yadav
Umesh C S
UC
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555-0647, USA.
Subramanyam
Sumitra
S
Ramana
Kota V
KV
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000284:Administration, Oral; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004926:Escherichia coli; D007962:Leukocytes / Q000276:immunology; D008070:Lipopolysaccharides; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013831:Thiamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014605:Uveitis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*
D000276:Adjuvants, Immunologic; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D011493:Protein Kinase C; D013831:Thiamine; C013835:benphothiamine