RGD Reference Report - Effects of topical indomethacin, bromfenac and nepafenac on lipopolysaccharide-induced ocular inflammation. - Rat Genome Database

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Effects of topical indomethacin, bromfenac and nepafenac on lipopolysaccharide-induced ocular inflammation.

Authors: Bucolo, C  Marrazzo, G  Platania, CB  Romano, GL  Drago, F  Salomone, S 
Citation: Bucolo C, etal., J Pharm Pharmacol. 2014 Jul;66(7):954-60. doi: 10.1111/jphp.12224. Epub 2014 Feb 12.
RGD ID: 9491782
Pubmed: PMID:24697218   (View Abstract at PubMed)
DOI: DOI:10.1111/jphp.12224   (Journal Full-text)

OBJECTIVES: To evaluate the effects of topical non-steroidal anti-inflammatory drugs (NSAIDs) on retinal vascular leakage, and inflammatory markers in endotoxin-induced uveitis (EIU) in rats. METHODS: EIU was induced in rats by lipopolysaccharide (LPS). Topical 0.5% indomethacin, 0.09% bromfenac and 0.1% nepafenac were given before and after LPS. Twenty-four hours after LPS, the animals were euthanized and plasma along with retina were collected to assess prostaglandin-E2 (PGE2 ) and C-reactive protein (CRP) levels using enzyme-linked immunosorbent assay. Retinal vascular leakage was assessed by Evans blue. Molecular modelling was used to evaluate interaction of compounds with cyclooxygenase-2 (COX-2). KEY FINDINGS: All NSAIDs tested significantly prevented PGE2 production with higher effect of indomethacin and bromfenac in comparison with nepafenac. The three drugs did not affect plasma CRP levels. The analysis of retinal vascular leakage revealed a significant (P<0.01) decrease after treatment with indomethacin, but no significant changes were observed after treatment with bromfenac and nepafenac. Indomethacin had a different interaction with COX-2 in comparison with bromfenac and amfenac (active metabolite of nepafenac). CONCLUSIONS: Topical treatment with indomethacin, bromfenac and nepafenac has significant anti-inflammatory effects. However, only indomethacin was able to prevent retinal vascular leakage in LPS-injected rats, likely due to the distinctive molecular mechanism.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Acute Uveitis  ISOCrp (Rattus norvegicus)9491782; 9491782protein:increased expression:plasma:RGD 
Acute Uveitis  IEP 9491782protein:increased expression:plasma:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Crp  (C-reactive protein)

Genes (Mus musculus)
Crp  (C-reactive protein, pentraxin-related)

Genes (Homo sapiens)
CRP  (C-reactive protein)


Additional Information