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F. Gasso, P. Bogdanov, J. Domingo; Docosahexaenoic Acid Improves Endogen Antioxidant Defense in Arpe-19 Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5932.
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Reactive oxygen species (ROS) are intimately involved in the oxidative damage of retina and its are used by mammalians cells as signaling molecules for redox regulation. Changes in the ratio of intracellular reduced and disulfide forms of glutathione (GSH/GSSG) can affect signaling pathways that participate in the redox status and in the development of the new anti-aging therapeutic agents.
Free radical initiator, 2,2'-azobis-(2-amidinopropane)-dihydrochloride (AAPH) and buthionine sulfoximina (BSO) were used in retina cells to induce the cellular damage associated with lipid peroxidation and DNA breaks. Generation of ROS was measured by the oxidation of fluorescent probes. Next, we examined the protective effects of DHA compounds and we measured the intracellular pool of GSH in BSO and AAPH-treated cells.
Using human retinal pigment epithelial cells as the experimental model, we demonstrated that nearly 50% of intracellular ROS could be removed when AAPH-treated cells were simultaneously incubated with docosahexaenoic acid-triglyceride (DHA-TG). After a treatment with DHA-TG, there was a great protection of the lipid peroxidation and the oxidative DNA damage. Moreover, this antioxidant activity proceeds via an increase of the intracellular GSH. The antioxidant activity of DHA-TG was dependent of DHA content and to the synthesis method. At the same DHA content, ethyl esther and free fatty acid forms shown a reduced antioxidant activity.
Our results demonstrate that DHA-TG may be very beneficial in the treatment of diseases associated with oxidative stress by detoxification of intracellular ROS. This increased antioxidant activity protects DNA of oxidative stress induced damage. In addition, DHA-TG promotes the endogenous antioxidant defense by increasing of GSH concentration. De novo synthesis of GSH contributes to decreasing the intracellular reactive oxygen species level. To our knowledge, this is the first report that shows on a specific and potent effect of DHA for decreasing the oxidative stress on human retinal pigment epithelial cells. This compound could be used as new anti-aging therapeutic agent by the health of the eye.
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