[Oxidative stress in uveitis and its correction with superoxide dismutase antioxidative enzyme (experimental study)].

OBJECTIVE: to study the influence of experimental uveitis on those biochemical parameters of aqueous humor that reflect inflammation acuity as well as local antioxidant and local antiproteolytic activity; to study the effect of topical superoxide dismutase (SOD) on the clinical course of uveitis and ocular metabolism. MATERIAL AND METHODS: Acute uveitis was induced in rabbits by a double injection (subcutaneous and intravitreal) of normal horse serum. The following parameters of aqueous humor were measured: protein concentration, antioxidant activity, SOD activity, alpha2-macroglobulin level, total nitrates and nitrites, and leukocyte number. Clinical assessment and histopathological study were performed. RESULTS: It was found that uveitis is associated with a statistically significant increase in protein concentration, leukocyte number, SOD activity, and alpha2-macroglobulin level in aqueous humor as well as a decrease in anti-hydroxyl radical activity. SOD instillations contributed to the reduction of the listed parameters and improvement of the antioxidant activity. Clinical presentations of uveitis also became less pronounced. CONCLUSION: SOD instillations for oxidative stress correction help reduce clinical presentations of uveitis, which is confirmed by biochemical examination.

[Experimental rationale for local use of angiotensin-converting enzyme inhibitors for the treatment of ocular tissue ischemia on a model of postburn conjunctival ischemia].

The authors have evaluated the local renin-angiotensin system on a model of experimental postburn conjunctival ischemia from the tear activity of angiotensin-converting enzyme (ACE) and studied whether impaired microcirculation might be restored by locally applying the ACE inhibitor captopril. It has been found that in conjunctival ischemia, there is a considerable increase in the activity of ACE, the key enzyme of the renin-angiotensin system, the activity of which largely determines the microcirculation in eye tissues. Instillations of the ACE inhibitor to rabbits within 2 weeks after alkaline burn of the eye result in a reduction in ACE activity and an earlier recovery of microcirculation in the area of conjunctival ischemia. Instillations of the ACE inhibitor captopril in ocular burn facilitate the maintenance of the tear antioxidant potential at the high level, which also suggests that the ACE inhibitor has a positive effect on the course of reparative processes after ocular burn injury. The findings suggest that it is promising to locally use ACE inhibitors for the treatment of ischemic processes in the eye.

[The in vitro cross-effects of inhibitors of renin-angiotensin and fibrinolytic systems on the key enzymes of these systems].

The effects of hypotensive agents (captopril, enalaprilate, and lisinopril) on the activities of components of the fibrinolytic system (FS) and the effects of antifibrinolytic agents (6-aminohexanoic acid (6-AHA) and tranexamic acid (t-AMCHA)) on the activities of angiotensin converting enzyme (ACE) were studied in vitro. Enalaprilate did not affect the FS activity. Captopril considerably inhibited the amidase activities of urokinase (u-PA), plasminogen tissue activator (t-PA), and plasmin ([I]50 (2.0-2.6) +/- 0.1 mM), and the activation of Glu-plasminogen affected by t-PA and u-PA ([I]50 (1.50-1.80) +/- 0.06 mM), which may be due to the presence of a mercapto group in the inhibitor molecule. Lisinopril did not affect the amidase activities of FS enzymes, but stimulated Glu-plasminogen and u-PA activation and inhibited activation of t-PA-fibrin-bound Glu-plasminogen ([I]50 (12.0 +/- 0.5) mM). Presumably, these effects can be explained by the presence in lisinopril of a Lys side residue, whose binding to lysine-binding Glu-plasminogen centers resulted, on the one hand, in the transformation of its closed conformation to a semi-open one and, on the other hand, in its desorption from fibrin. Unspecific inhibition of the activity of ACE, a key enzyme of the renin-angiotensin system, in the presence of 6-AHA and t-AMCHA ([I]50 10.0 +/- 0.5 and 7.5 +/- 0.4 mM, respectively) was found. A decrease in the ACE activity along with the growth of the fibrin monomer concentration was revealed. The data demonstrate that, along with endogenous mediated interactions, relations based on the direct interactions of exogenous inhibitors of one system affecting the activities of components of another system can take place.

[Mental rationale for local use of angiotensin-converting enzyme in the treatment of inflammatory processes in the eye].

A rabbit model of deep alkaline-induced corneal burn was used to study the involvement of the local renin-angiotensin system of the eye in the development of an inflammatory process and wound healing. Corneal burn injury was shown to cause a significant increase in the activity of angiotensin-converting enzyme (ACE) in the tear and internal ocular tissue structures, promoting their microcirculatory disorders and inflammation development. The local use of ACE inhibitors as instillations substantially reduces an inflammatory reaction and the incidence of deep and extensive corneal ulcers. The study performed provides experimental rationale for the local use of ACE inhibitors for the treatment of inflammatory processes in the eye.