THE EFFECT OF N-ACETYLCYSTEINE AND DEXAMETHASONE PARENTERAL ADMINISTRATION ON THE BIOCHEMICAL PROCESSES IN THE AQUEOUS HUMOR OF THE ANTERIOR CHAMBER OF THE EYES IN RABBITS WITH EXPERIMENTAL IMMUNOGENIC UVEITIS

Abstract

Objective. To evaluate the impact and compare the efficiency of parenteral administration of N-acetylcysteine (NAC) and dexamethasone when used as monotherapy or combination therapy in the treatment of experimental immunogenic uveitis (EIU) in rabbits, as well as to explore the changes of biochemical parameters in the aqueous humor of the eyes in experimental animals. Material and Methods. An experimental study was performed on 45 rabbits (90 eyes). Of these 5 healthy intact rabbits (10 eyes) served as a control group. Acute immunogenic uveitis was caused in 40 rabbits by injecting normal horse serum subcutaneously (5 ml) and then intravitreally (0.07 ml). The animals with experimental uveitis were divided into 8 groups (5 animals each). The first 4 groups – control-1, experiment-1, control-3, experiment-3 – received daily intramuscular injections of placebo, NAC, dexamethasone or a combination of NAC and dexamethasone respectively for 3 days, and thereafter they were withdrawn from the experiment. The remaining 4 groups – control-2, experiment-2, control-4, experiment-4 received, respectively, daily intramuscular injections of placebo, NAC, dexamethasone, a combination of NAC and dexamethasone for 7 days, and after that they were also withdrawn from the experiment. The drugs in the aforementioned groups were used from the moment of the horse serum intravitreal injection. When withdrawing animals from the experiment, aqueous humor was taken from the anterior chamber of their eyes, followed by the evaluation of protein (albumin) concentration and the number of leukocytes. Results. A significant elevation of albumin and the number of leukocytes in the aqueous humor of the eyes in the rabbits with experimental immunogenic uveitis was noted. NAC effectively reduced the level of albumin and the number of leukocytes in the aqueous humor. Dexamethasone showed more efficacy in reducing the investigated aqueous humor biochemichal parameters than NAC. Nevertheless, a synergism of the pharmacological action of NAC and dexamethasone was detected, since their combination had the greatest potency in reduction of albumin level and the number of leukocytes in the aqueous humor of the eyes in the rabbits with experimental immunogenic uveitis, even though the dosage of dexamethasone in the groups with combined (NAC and dexamethasone) therapy was reduced by 50% (1 mg / kg body weight). Conclusion. Parenteral administration of NAC significantly reduces inflammation in EIU. Combination of NAC and dexamethasone showed synergy of action in reducing the intensity of inflammatory process in rabbits with EIU, which is an objective rationale for including NAC in the complex therapy of uveitis, which in turn will reduce a single or course dose of dexamethasone and lower the risks of side effects caused by glucocorticoids.