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Abstract #19123 Published in IGR 3-1
Latanoprost exerts neuroprotective activity in vitro and in vivo
Drago F; Valzelli S; Emmi I; Marino A; Scalia CC; Marino VExperimental Eye Research 2001; 72: 479-486
Prostaglandins may influence cyclo-oxygenase (COX-2) and nitric oxide (NO) synthase activity, thus interfering with ischemia-induced neurotoxic processes. The prostaglandin synthetic derivative, latanoprost was tested in different in vivo and in vitro models of neuronal damage in order to study its influence on these processes. Ischemia was induced in rats by bilateral occlusion of the carotid arteries for 30 minutes. Latanoprost (0.01 mg x kg-1 per die, i.p. for three days) or the ionotropic glutamate receptors antagonist, MK-801 (0.1 mg x kg-1 per die, i.p. for three days) were equal in preventing lactate accumulation in retinal tissue of animals subjected to acute ischemia. Similar results were obtained in animals with retinal ischemia induced by increasing intraocular pressure to 120 mmHg for 45 minutes. PGF2α, PGE2, latanoprost and acid of latanoprost (PhXA85) reduced the release of LDH from primary cultures of human retinal cells in vitro subjected to glutamate (10 μm) or hypoxia/re-oxygenation exposure. This effect was observed only at concentrations of 1-0.01 μm for PGF2α and PGE2, and of 0.1-0.001 μm for latanoprost (0.01 μm-0.1 nM for PhXA85). The COX-2 activity in cultured retinal cells exposed to glutamate was measured as PGE2 production when latanoprost was applied compared to arachidonic acid (AA) at different molar concentrations. The COX-2 activity was reduced by arachidonic acid (0.1-0.01 μm) as well as by latanoprost (0.1-0.001 μm) and PhXA85 (0.01-0.001 μm) in retinal cells exposed to glutamate. Inhibition of inducible NO synthase was also found with the same drug concentrations. These results suggest that latanoprost exerts a neuroprotective activity in vitro and in vivo. This effect seems to be present only at low concentrations of the drug. A negative feedback on neuronal COX-2 activity may be possibly involved.
Dr F. Drago, Department of Experimental and Clinical Pharmacology, University of Catania Medical School, Catania, Italy. fdrago@tin.it
Classification:
11.4 Prostaglandins (Part of: 11 Medical treatment)