Abstract
Purpose: :
To investigate the efficacy of ethyl pyruvate (EP) in preventing the bacterial endotoxin, lipopolysaccharide (LPS) -induced ocular inflammation in rats.
Methods: :
Endotoxin-induced uveitis (EIU) in Lewis rats was developed by subcutaneous injection of 150 ug LPS. Respective groups also received EP (30 mg/kg body wt, i.p) or vehicle 1 h prior to LPS injection. After 3 and 24 h of LPS injection, animals were sacrificed, enucleated the eyes, and aqueous humor (AqH) was collected. The number of infiltrating cells, total protein, and the levels of various cytokines and chemokines were measured in AqH. Immunohistochemical analysis was performed in ocular tissue sections to determine the expression of TNF-α and phospho-NF-kB. Primary non-pigment ciliary epithelial cells from human (HNPECs) were used as an in vitro model to determine the efficacy of EP on LPS-induced inflammatory response.
Results: :
EP significantly prevented the endotoxin -induced increase in the number of infiltrating cells, total protein, and inflammatory cytokines/chemokines in AqH. EP also suppressed the expression of TNF-α and activation of phospho-NF-kB in ciliary body and retinal tissues of the EIU rat eyes. Further, EP inhibited the LPS-induced activation of NF-kB and expression of Cox-2, iNOS and TNF-α in HNPECs.
Conclusions: :
Our results indicate that the treatment of EP prevents ocular inflammation in rats and therefore EP could be used for ameliorating uveitis complications.
Keywords: uveitis-clinical/animal model • inflammation • signal transduction: pharmacology/physiology