Article

Lornoxicam protects mouse cornea from UVB-induced damage via inhibition of NF-{kappa}B activation.

Department of Ophthalmology, Jinling Hospital, School of Medicine of Nanjing University, 305 East Zhongshan Road, Nanjing 210002, People's Republic of China.
The British journal of ophthalmology (Impact Factor: 2.92). 05/2008; 92(4):562-8. DOI: 10.1136/bjo.2007.129064
Source: PubMed

ABSTRACT Ultraviolet B (UVB) irradiation activates nuclear factor-kappa B (NF-kappaB) and cyclo-oxygenase (COX). The COX inhibitors are protective against UVB-induced skin damage. The aim of this study is to determine the effect of lornoxicam, a potent COX inhibitor, on UVB-induced corneal damage and its mechanism in a mouse model.
Eighty female ICR mice were randomly divided into four groups. Corneal damage was graded based on the degree of haze. NF-kappaB activation in the cornea was examined using an electrophoretic mobility shift assay, and tumour necrosis factor (TNF)-alpha production was determined by enzyme-linked immunosorbant assay (ELISA) 6, 24 and 72 h after irradiation. The histopathological changes in cornea were examined under the transmission electronic microscope at 24 h up to 7 days following irradiation.
UVB irradiation (1.2 J/cm(2)) induced a significant and sustained increase in the NF-kappaB-DNA binding activity and TNF-alpha production in the cornea, with the peak at 24 h. Apparent stromal oedema and corneal opacity as well as severe histopathological damage including epithelial exfoliation, keratocyte loss and endothelial oedema were observed after irradiation. Treatment with lornoxicam (0.4 mg/kg, intraperitoneal) significantly lowered the grade of corneal opacity and remarkably ameliorated the ultrastructural damage induced by irradiation. Lornoxicam treatment significantly suppressed UVB-induced increases in NF-kappaB-DNA binding and TNF-alpha expression.
Lornoxicam treatment attenuates UVB-induced corneal damage via inhibition of NF-kappaB activation.

0 Bookmarks
 · 
77 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We designed the current study to determine the protective effects of lornoxicam, a cyclooxygenase (COX) inhibitor, on recurrent herpetic stromal keratitis (HSK) and the nuclear factor-kappaB (NF-kappaB)-mediated mechanism in mice. A corneal latent herpes simplex virus-1 (HSV-1) infected mouse model was established. Six weeks later, Ultraviolet B (UVB) irradiation induced the recurrence. Corneal swabs were obtained and cultured with indicator cells to determine shedding of the virus. Lornoxicam was administered intraperitoneally daily, beginning one day before irradiation and lasting for seven days. Saline-treated and mock-infected control groups were also studied at the same time. Development of corneal inflammation and opacity was scored. Immunohistochemical staining and an electrophoretic mobility shift assay were performed to evaluate the effect of lornoxicam on NF-kappaB activation in the corneal tissues. The levels of tumor necrosis factor-alpha (TNF-alpha) in the cornea were determined by an enzyme-linked immunosorbent assay (ELISA). HSV-1 reactivation induced stromal edema and opacification concomitantly with elevated activation of NF-kappaB and elevated production of TNF-alpha. Lornoxicam treatment significantly decreased the incidence of recurrent HSK, attenuated the corneal opacity scores, and also effectively suppressed both NF-kappaB activation and TNF-alpha expression in biological analysis. Histopathology examination revealed a reduced immunostaining positive cell density for NF-kappaB in the cornea from lornoxicam-treated mice as well as a diminished inflammatory response. Lornoxicam exerts protective effects against HSK, presumably through the down-regulation of NF-kappaB activation.
    Molecular vision 02/2009; 15:1252-9. · 1.99 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Ultraviolet B (UVB) irradiation activates nuclear factor-kappa B (NF-κB) and inducible nitric oxide synthase (iNOS) in the cornea, resulting in inflammatory responses and malondialdehyde (MDA) accumulation. This study aims to determine the effect of zerumbone, a potent NF-κB inhibitor and inflammation modulators, on UVB-induced corneal damages in a mouse model. Fifty female imprinting control region (ICR) mice were randomly divided into five groups. The mice were anaesthetized with their ocular surfaces exposed to UVB light (0.72J/cm(2)/daily), followed by daily dietary zerumbone supplements at 0, 1, 10, and 100 mg/kg of bodyweight. Mice without zerumbone supplements were used as treatment controls and mice without UVB irradiation as blank controls. Corneal surface damages were graded according to smoothness, opacity, and the extent of lissamine green staining. Histopathological changes were also examined, along with the expression of NF-κB, iNOS, and tumor necrosis factor-α (TNF-α). MDA accumulation and the levels of two antioxidant enzymes, glutathione (GSH) and GSH reductase (GR) were also examined. UVB irradiation caused significant damages to cornea, including sustained inflammation, apparent corneal ulcer, and severe epithelial exfoliation, leading to thinning of corneal epithelial layer, and infiltration of polymorphonuclear leukocytes. NF-κB expression was highly activated with nuclear translocation. The expression of iNOS and TNF-α were increased. MDA accumulation was also increased in both the corneal epithelial layer and the stroma. With dietary zerumbone, corneal damages were ameliorated in a dose-dependent manner. NF-κB activation and its nuclear translocation were blocked with decreased expression of iNOS and TNF-α. Infiltration of polymorphonuclear leukocytes was also blocked by dietary zerumbone. Besides, MDA accumulation was reduced with concomitant increase of GSH and GR levels. Dietary zerumbone prevents UVB-induced corneal damages by inhibition of NF-κB, iNOS, and TNF-α, with concomitant reduction of MDA accumulation and increase of GSH and GR levels in the mouse model. Results of this study suggest that dietary zerumbone may be used as a prophylactic agent against UVB-induced photokeratitis.
    Molecular vision 01/2011; 17:854-63. · 1.99 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The nuclear factor-κB (NF-κB) is a key transcription factor pathway that is responsible for many key biological processes, such as inflammation, apoptosis, stress response, corneal wound healing, angiogenesis, and lymphangiogenesis. Numerous recent studies have investigated NF-κB in the context of ocular surface disorders, including chemical injury, ultraviolet radiation-induced injury, microbial infections, allergic eye diseases, dry eye, pterygium, and corneal graft rejection. The purpose this article is to summarize key findings with regard to the pathways regulating NF-κB and processes governed by the NF-κB pathway. In the innate defense system, NF-κB is involved in signaling from the toll-like receptors 2, 3, 4, 5 and 7, which are expressed in conjunctival, limbal, and corneal epithelial cells. These determine the ocular responses to infections, such as those caused by Pseudomonas aeruginosa, Staphylococcus aureus, adenovirus, and herpes simplex-1 virus. Natural angiogenic inhibitors enhance NF-κB, and this may occur through the mitogen-activated protein kinases and peroxisome proliferator-activated receptor γ. In alkali injury, inhibition of NF-κB can reduce corneal angiogenesis, suggesting a possible therapeutic strategy. The evaluation of NF-κB inhibitors in diseases is also discussed, including emodin, besifloxacin, BOL-303242-X (mapracorat), thymosin-β4, epigallocatechin gallate, Perilla frutescens leaf extract and IKKβ-targeting short interfering RNA.
    The ocular surface 07/2012; 10(3):137-48. · 2.64 Impact Factor

Full-text

View
1 Download
Available from