Degradation of widely used antiglaucoma drugs mediated by photo-generated reactive oxygen species

IF 4.4 3区化学 Q2 CHEMISTRY, PHYSICAL

Journal of Photochemistry and Photobiology A-chemistry Pub Date : 2026-09-01 Epub Date: 2026-03-03 DOI:10.1016/j.jphotochem.2026.117158

Charis Parramón Jurado , Cecilia Liaudat , Marcela Altamirano , Cecilia Challier , Susana Criado

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Abstract

Reactive oxygen species (ROS) are produced as by-products of oxygen metabolism and play an essential role in biological systems. In the eye, ROS can also be generated through the photosensitizing action of natural pigments like riboflavin. Disruption of the balance between ROS production and the antioxidant defense system leads to oxidative stress, which contributes to the development and progression of ocular diseases such as glaucoma. Under these conditions, oxidative degradation may occur in ophthalmic drugs used to treat glaucoma, potentially reducing their therapeutic efficacy and generating toxic products.

This study investigates the ROS-mediated degradation of widely used antiglaucoma drugs dorzolamide (DZ), ethoxzolamide (ET) and brimonidine tartrate (BT) in the presence of riboflavin and rose bengal as photosensitizers. Photochemical and spectroscopic analyses confirmed that these drugs interact with the electronically excited states of riboflavin and with various photo-generated ROS from these states, undergoing oxidative degradation via Type I and Type II mechanisms. The antiglaucoma drugs also exhibited pro-oxidant capacity, being able to generate O₂(¹Δ_g) upon direct irradiation and self-degrading under these conditions.

Furthermore, the potential cytotoxic effects of the degradation products were evaluated using human MRC-5 cells. The results showed that neither the drugs nor their oxidation products were significantly cytotoxic under the current experimental conditions.

These findings emphasize the importance of considering oxidative stability when formulating ophthalmic drugs, offering valuable insights into their behavior under oxidative stress scenarios.

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光生成活性氧介导的广泛应用的抗青光眼药物的降解

活性氧（ROS）是氧代谢的副产物，在生物系统中起着至关重要的作用。在眼睛中，ROS也可以通过核黄素等天然色素的光敏作用产生。ROS生成和抗氧化防御系统之间的平衡被破坏导致氧化应激，这有助于青光眼等眼部疾病的发生和进展。在这些条件下，用于治疗青光眼的眼科药物可能发生氧化降解，可能降低其治疗效果并产生有毒产物。本研究研究了在核黄素和玫瑰红作为光敏剂存在下，ros介导的抗青光眼药物多唑胺（DZ）、乙氧唑胺（ET）和酒石酸溴胺（BT）的降解。光化学和光谱分析证实，这些药物与核黄素的电子激发态以及由这些状态产生的各种光生ROS相互作用，通过I型和II型机制进行氧化降解。抗青光眼药物也表现出促氧化能力，能够在直接照射下产生O2(1Δg)，并在这些条件下自降解。此外，利用人MRC-5细胞评估了降解产物的潜在细胞毒性作用。结果表明，在目前的实验条件下，药物及其氧化产物均没有明显的细胞毒性。这些发现强调了在制定眼科药物时考虑氧化稳定性的重要性，为它们在氧化应激情景下的行为提供了有价值的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Photochemistry and Photobiology A-chemistry 化学-物理化学

CiteScore

7.90

自引率

7.00%

发文量

580

审稿时长

48 days

期刊介绍： JPPA publishes the results of fundamental studies on all aspects of chemical phenomena induced by interactions between light and molecules/matter of all kinds. All systems capable of being described at the molecular or integrated multimolecular level are appropriate for the journal. This includes all molecular chemical species as well as biomolecular, supramolecular, polymer and other macromolecular systems, as well as solid state photochemistry. In addition, the journal publishes studies of semiconductor and other photoactive organic and inorganic materials, photocatalysis (organic, inorganic, supramolecular and superconductor). The scope includes condensed and gas phase photochemistry, as well as synchrotron radiation chemistry. A broad range of processes and techniques in photochemistry are covered such as light induced energy, electron and proton transfer; nonlinear photochemical behavior; mechanistic investigation of photochemical reactions and identification of the products of photochemical reactions; quantum yield determinations and measurements of rate constants for primary and secondary photochemical processes; steady-state and time-resolved emission, ultrafast spectroscopic methods, single molecule spectroscopy, time resolved X-ray diffraction, luminescence microscopy, and scattering spectroscopy applied to photochemistry. Papers in emerging and applied areas such as luminescent sensors, electroluminescence, solar energy conversion, atmospheric photochemistry, environmental remediation, and related photocatalytic chemistry are also welcome.