The Inhibitory Effect of Oxibiol on the Process of Protein Modification by Water-Soluble Products of Photo-Oxidative Destruction of Bisretinoid A2E

IF 4.033 Q4 Biochemistry, Genetics and Molecular Biology Biophysics Pub Date : 2024-09-27 DOI:10.1134/S0006350924700246

A. E. Dontsov, N. L. Aronshtam, M. A. Ostrovsky

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Abstract

We have previously shown that the heteroaromatic antioxidant oxibiol (N-acetylcysteinate 6-hydroxy-2-aminobenzothiazole) inhibited the process of fructosylation of serum albumin. The purpose of this study was to elucidate the inhibitory effect of oxibiol on protein modification by photodestruction products of bisretinoid A2E, the main fluorophore of lipofuscin granules of retinal pigment epithelium cells of the human eye. It was found that the water-soluble fraction obtained from A2E-liposomes irradiated with visible light, unlike the water-soluble fraction from nonirradiated A2E-liposomes, significantly modified albumin after a day of incubation at 37°C. Oxibiol at millimolar concentrations effectively inhibited this process. The inhibitory effect of oxibiol was probably based on its antioxidant activity and the ability to competitively interact with reactive aldehydes formed during the photo-oxidative destruction of A2E-cardiolipin liposomes. The acute toxicity of oxibiol in mice with intraperitoneal administration was studied and the values of LD₁₀ and LD₅₀ were determined. The results indicated the promising use of oxibiol in pharmacology for the prevention and treatment of diseases associated with the development of oxidative stress in various fields of medicine, primarily in ophthalmology.

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羰基二醇对双维甲酸 A2E 光氧化破坏的水溶性产物修饰蛋白质过程的抑制作用

我们曾研究发现，杂芳香族抗氧化剂oxibiol（N-乙酰半胱氨酸-6-羟基-2-氨基苯并噻唑）可抑制血清白蛋白的果糖基化过程。本研究的目的是阐明oxibiol 对人眼视网膜色素上皮细胞脂褐质颗粒的主要荧光团双翠绿素 A2E 的光破坏产物对蛋白质修饰的抑制作用。研究发现，与未经过辐照的 A2E 脂质体的水溶性部分不同，经过可见光辐照的 A2E 脂质体的水溶性部分在 37°C 孵育一天后会显著改变白蛋白。毫摩尔浓度的羰基二醇可有效抑制这一过程。oxibiol的抑制作用可能是基于其抗氧化活性以及与A2E-心磷脂脂质体在光氧化破坏过程中形成的活性醛竞争性相互作用的能力。研究了小鼠腹腔注射 Oxibiol 的急性毒性，并确定了 LD10 和 LD50 的值。研究结果表明，oxibiol 在药理学中的应用前景广阔，可用于预防和治疗各医学领域（主要是眼科领域）与氧化应激发展相关的疾病。

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来源期刊

Biophysics Biochemistry, Genetics and Molecular Biology-Biophysics

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1.20

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0.00%

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期刊介绍： Biophysics is a multidisciplinary international peer reviewed journal that covers a wide scope of problems related to the main physical mechanisms of processes taking place at different organization levels in biosystems. It includes structure and dynamics of macromolecules, cells and tissues; the influence of environment; energy transformation and transfer; thermodynamics; biological motility; population dynamics and cell differentiation modeling; biomechanics and tissue rheology; nonlinear phenomena, mathematical and cybernetics modeling of complex systems; and computational biology. The journal publishes short communications devoted and review articles.