advertisement
Abstract #19359 Published in IGR 9-3
Hemin, an inducer of heme oxygenase-1, lowers intraocular pressure in rabbits
Privitera MG; Potenza M; Bucolo C; Leggio GM; Drago FJournal of Ocular Pharmacology and Therapeutics 2007; 23: 232-239
AIM: Carbon monoxide (CO) generated from heme may induce vasodilation and exert cyto-protective properties in the eye. This study was undertaken to investigate the effects of hemin, a potent inducer of heme oxygenase-1 (HO-1), on models of ocular hypertension in rabbits. METHODS: Ocular hypertension was induced by injecting α-chymotrypsin in both eyes under local anesthesia. Only rabbits with an intraocular pressure (IOP) of 25 mmHg or more were used. The dose-response study of the hemin effect on IOP was made by an intravenous injection of the drug (50, 75, and 100 mg/kg) and subsequent IOP monitoring every 6 h. A separate set of animals was pretreated with the HO-1 inhibitor, zinc protoporphyrin-IX (ZnPP-IX, 0.1 mg/kg) 6 h before the vehicle or a 100-mg/kg hemin injection. Ocular hypertension was also obtained by the subconjunctival injection of betamethasone 21-phosphate disodium (4 mg/mL) in both eyes every week for 4 weeks. Only animals with an IOP of 30 mmHg or more were included in the experimental session. A group of these animals was pretreated with ZnPP-IX (0.1 mg/kg) 6 h before the vehicle or a 100-mg/kg hemin injection, and IOP was assessed every 6 hours. RESULTS: Hemin caused a significant dose-related reduction of IOP in rabbits with α-chymotrypsin- induced ocular hypertension. No significant effect was observed in the normotensive eyes of the control animals or on pupil diameter. Pretreatment with the HO-1 inhibitor, ZnPP-IX, abolished the decrease of IOP that was induced by the maximum dose of hemin (100 mg/kg). A similar reduction in IOP was observed in those rabbits with betamethasone-induced ocular hypertension who were treated with 100 mg/kg of hemin. Furthermore, pretreatment with ZnPP-IX prevented the hemin effect on IOP. CONCLUSIONS: The induction of HO-1 by hemin leads to a reduction of IOP in the α-chymotrypsin and betamethasone models of ocular hypertension. These results suggest an involvement of CO in the regulation of ocular pressure in rabbits.
Dr. F. Drago, Department of Experimental and Clinical Pharmacology, University of Catania Medical School, Viale A. Doria 6, 95125 Catania, Italy. f.drago@unict.it
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
5.3 Other (Part of: 5 Experimental glaucoma; animal models)