Search Results (2)

Dry eye syndrome (DES) is characterized by decreased tear production and stability, leading to desiccating stress, inflammation and corneal damage. DES treatment may involve targeting the contributing inflammatory pathways mediated by polyunsaturated fatty acids and their derivatives, oxylipins. Here, using an animal model of general anesthesia-induced DES, we addressed these pathways by characterizing inflammatory changes in tear lipidome, in correlation with pathophysiological and biochemical signs of the disease. The decline in tear production was associated with the infiltration of inflammatory cells in the corneal stroma, which manifested one to three days after anesthesia, accompanied by changes in tear antioxidants and cytokines, resulting in persistent damage to the corneal epithelium. The inflammatory response manifested in the tear fluid as a short-term increase in linoleic and alpha-linolenic acid-derived oxylipins, followed by elevation in arachidonic acid and its derivatives, leukotriene B4 (5-lipoxigenase product), 12-hydroxyeicosatetraenoic acid (12-lipoxigeanse product) and prostaglandins, D2, E2 and F2α (cyclooxygenase products) that was observed for up to 7 days. Given these data, DES was treated by a novel ophthalmic formulation containing a dimethyl sulfoxide-based solution of zileuton, an inhibitor of 5-lipoxigenase and arachidonic acid release. The therapy markedly improved the corneal state in DES by attenuating cytokine- and oxylipin-mediated inflammatory responses, without affecting tear production rates. Interestingly, the high efficacy of the proposed therapy resulted from the synergetic action of its components, namely, the general healing activity of dimethyl sulfoxide, suppressing prostaglandins and the more specific effect of zileuton, downregulating leukotriene B4 (inhibition of T-cell recruitment), as well as upregulating docosahexaenoic acid (activation of resolution pathways). Full article

Endogenous melatonin is a known free radical scavenger that removes reactive oxygen species (ROS), thus, alleviating oxidative stress. The purpose of this study was to demonstrate its effect against kainic acid (KA)-induced oxidative stress in organotypic hippocampal slice cultures (OHSCs). To observe neuroprotective effects of melatonin, different concentrations (0.01, 0.1 and 1 mM) of melatonin were administrated after KA treatment for 18 h in OHSCs of rat pups. Dose-response studies showed that neuronal cell death was significantly reduced after 0.1 and 1 mΜ melatonin treatments based on propidium iodide (PI) uptake and cresyl violet staining. The dichlorofluorescein (DCF) fluorescence which indicates ROS formation decreased more in the melatonin-treated group than in the KA group. The expression of 5-lipoxigenase (5-LO) and caspase-3 were reduced in the melatonin-treated groups compared to the KA group. These results suggest that melatonin may be an effective agent against KA-induced oxidative stress in the OHSC model. Full article