lornoxicam and Corneal-Opacity

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.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Line; Corneal Opacity; Corneal Stroma; Disease Models, Animal; Down-Regulation; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression; Herpesvirus 1, Human; Humans; Immunohistochemistry; Keratitis, Herpetic; Mice; Mice, Inbred ICR; NF-kappa B; Piroxicam; Tumor Necrosis Factor-alpha; Ultraviolet Rays; Virus Shedding

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.

Topics: Animals; Cornea; Corneal Opacity; Female; Mice; Mice, Inbred ICR; Microscopy, Electron; NF-kappa B; Piroxicam; Radiation Injuries, Experimental; Radiation-Protective Agents; Random Allocation; Tumor Necrosis Factor-alpha; Ultraviolet Rays