Abstract
Abstract: :
Purpose: To investigate the effects of hemin, a potent inducer of heme oxygenase–1 (HO–1), on alpha–chymotrypsin–iduced hypertensive rabbits. Methods: New Zealand albino rabbits were used; the animals were handled according to the ARVO Resolution on the Use of Animals in Research. Ocular hypertension was induced by injection of alpha–chymotrypsin (50 UAE, Pharmacopèe Française) into the eye of animals anaesthetized by an i.m. injection of 35 mg/kg ketamine HCl and 5 mg/kg xylazine HCl. Intraocular pressure (IOP) was evaluated after four weeks and only rabbits in which pressure became 12–15 mmHg higher than in the untreated eye were used. IOP was measured by using a Tono–Pen XL tonometer. Hemin was dissolved in saline and 20% Tween 80 (vehicle) administered by i.v. injection (1, 10, 100 mg/kg) and the IOP was monitored. A separate set of animals was pre–treated with ZnPP–IX, an HO–1 inhibitor, (0.1 mg/kg) 6 hours before the administration of hemin at the highest dose (100 mg/kg). The pupil diameter (PD) was measured with a Castroviejo caliper. Results: The administration of hemin significantly (p<0.01) lowered the IOP of α–chymotrypsinized rabbits, after 24 hours from injection, in a dose–related manner, with a maximum drop of 9 mmHg after administration of 100 mg/kg. Hemin at the lowest concentration (1 mg/kg) did not cause any significant reduction of IOP compared to the vehicle group. The administration of the HO–1 inhibitor ZnPP–IX significantly (p<0.01) abolished the decrease of IOP induced by hemin. Hemin did not cause any significant change of pupil diameter in ocular normotensive rabbits. Conclusions: This study provides the first evidence that the induction of HO–1 by hemin reduced the IOP in alpha–chymotrypsin–induced hypertensive rabbits. Therefore hemin and more in general the HO–1 inducers (i.e. phenolic compounds) may offer a novel class of agents potentially effective in the modulation of ocular hypertension.
Keywords: intraocular pressure • nitric oxide • inflow/ciliary body