Preventive and therapeutic effects of SkQ1-containing Visomitin eye drops against light-induced retinal degeneration.

The human retina is constantly affected by light of varying intensity, this being especially true for photoreceptor cells and retinal pigment epithelium. Traditionally, photoinduced damages of the retina are induced by visible light of high intensity in albino rats using the LIRD (light-induced retinal degeneration) model. This model allows study of pathological processes in the retina and the search for retinoprotectors preventing retinal photodamage. In addition, the etiology and mechanisms of retina damage in the LIRD model have much in common with the mechanisms of the development of age-related retinal disorders, in particular, with age-related macular degeneration (AMD). We have studied preventive and therapeutic effects of Visomitin eye drops (based on the mitochondria-targeted antioxidant SkQ1) on albino rat retinas damaged by bright light. In the first series of experiments, rats receiving Visomitin for two weeks prior to illumination demonstrated significantly less expressed atrophic and degenerative changes in the retina compared to animals receiving similar drops with no SkQ1. In the second series, the illuminated rats were treated for two weeks with Visomitin or similar drops without SkQ1. The damaged retinas of the experimental animals were repaired much more effectively than those of the control animals. Therefore, we conclude that Visomitin SkQ1-containing eye drops have pronounced preventive and therapeutic effects on the photodamaged retina and might be recommended as a photoprotector and a pharmaceutical preparation for the treatment of AMD in combination with conventional medicines.

Dietary tomato paste protects against ultraviolet light-induced erythema in humans.

Carotenoids are efficient antioxidants capable of scavenging reactive oxygen species generated under conditions of photooxidative stress. It has been shown that supplementation with high doses of beta-carotene protects skin against UV-induced erythema. This study was designed to investigate whether intervention with a natural dietary source rich in lycopene protects against UV-induced erythema in humans. Tomato paste (40 g), providing approximately 16 mg/d of lycopene, was ingested with 10 g of olive oil over a period of 10 wk by 9 volunteers. Controls (n = 10) received olive oil only. Erythema was induced by illumination of dorsal skin (scapular region) with a solar simulator at the beginning of the study, after 4 wk and after 10 wk. Intensity of erythema was measured by chromatometry; the a-value was determined directly before and 24 h after irradiation. Serum carotenoid levels were measured by HPLC. At the beginning of the study, carotenoid levels did not differ between the two groups. Serum levels of lycopene increased in supplemented subjects; the other carotenoids did not change significantly, and no change in serum carotenoids was observed in the control group. At wk 10, dorsal erythema formation was 40% lower in the group that consumed tomato paste compared with controls (P = 0.02; Wilcoxon-Mann-Whitney test). No significant difference between groups was found at wk 4 of treatment. The data demonstrate that it is feasible to achieve protection against UV light-induced erythema by ingestion of a commonly consumed dietary source of lycopene.

Somatostatin inhibits the production of vascular endothelial growth factor in human glioma cells.

In various cell types, the neuro- and endocrine peptide somatostatin induces inhibitory and anti-secretory effects. Since somatostatin receptors, especially of the subtype sst2A, are constantly over-expressed in gliomas, we investigated the influence of somatostatin and the receptor subtype-selective peptide/non-peptide agonists octreotide and L-054,522 on the secretion of the most important angiogenesis factor produced by gliomas, vascular endothelial growth factor (VEGF). Cultivated cells from solid human gliomas of different stages and glioma cell lines secreted variable amounts of VEGF, which could be lowered to 25% to 80% by co-incubation with somatostatin or sst2-selective agonists (octreotide and L-054,522). These effects were dose-dependent at nanomolar concentrations. Stimulation with different growth factors (EGF, bFGF) or hypoxia considerably increased VEGF production over basal levels. Growth factor-induced VEGF synthesis could be suppressed to <50% by co-incubation with somatostatin or an sst2-selective agonist; this was less pronounced in hypoxia-induced VEGF synthesis. The effects were detected at the protein and mRNA levels. These experiments indicate a potent anti-secretory action of somatostatin or sst2 agonists on human glioma cells that may be useful for inhibiting angiogenesis in these tumors.

Profiles of antioxidants in human plasma.

The profile of antioxidants in biological fluids and tissues may be helpful in assessing oxidative stress in humans. Plasma antioxidants can be decreased as compared to established normal values, in abnormal or subnormal conditions, for instance as a consequence of disease-related free radical production. Alternatively, plasma antioxidants may be below the normal range due to insufficient dietary supply. Therefore, the profile of antioxidants can be of use only in conjunction with other parameters of the oxidative stress status. This article examines the profiles of plasma antioxidants in oxidative stress-related conditions, e.g., diabetes and some other diseases, as well as smoking and smoking cessation.