Reactive oxygen species mediated-degradation of antiglaucoma drugs. An approach to oxidative stress conditions

Reactive oxygen species (ROS) are generated as by-products of oxygen metabolism and play multiple roles in biological systems. In addition, these species can be generated in the eye as a result of the photosensitizing action of pigments that are naturally present in this organ, such as riboflavin. An imbalance between the production of ROS and the response of the antioxidant defense system results in oxidative stress.

In humans, the oxidative stress can lead to the initiation or development of many ocular diseases and injuries (glaucoma, cataracts, macular degeneration). In this highly oxidative cellular environment, topically administered drugs for the treatment of various pathologies may be susceptible to be attacked by ROS and consequently degraded, losing their clinical efficacy or generating toxic products.

In this contribution, the kinetics of ROS-mediated degradation of the antiglaucoma drugs, acetazolamide and methazolamide, was investigated. In order to analyze the effects that these drugs and their derivatives produce on the viability of normal human cells, this parameter was evaluated in the MRC-5 line.

Results showed that acetazolamide and methazolamide interact with the electronic triplet state of riboflavin and with different photo-generated ROS from this state. Both drugs were chemically degraded by singlet oxygen, although methazolamide was more reactive than acetazolamide. The experiments demonstrated that neither the drugs nor their ROS-mediated oxidation products exhibited cytotoxicity in the MRC-5 cell line.

On the other hand, under direct UV irradiation, AZ and MZ generated O₂(¹Δ_g) with considerable efficiency compared to other ophthalmic drugs and would be considered good sensitizers.