Introduction: Sulodexide (SDX) is used for the treatment of many vascular disorders due to its anticoagulant, anti-inflammatory and anti-atherosclerotic properties. However, the detailed molecular mechanism of its endothelioprotective action is still not completely understood. There is increasing evidence suggesting that antioxidant enzymes play an important role in anti-ischemic properties of SDX. We postulate that up-regulation of glutathione-S-transferase P1 (GSTP1) mediated by the transcription factor Nrf2 could be associated with the antioxidant effect of SDX on vascular endothelial cells. Material and methods: In the present study, we investigated whether SDX affects GSTP1 and Nrf2 in oxygen glucose deprivation (OGD) treated human umbilical vein endothelial cells (HUVECs). The cells treated with/without SDX (0.5 LRU/ml) were subjected to OGD for 1-6 h. To study the influence of SDX on the Nrf2 nucleus accumulation, the cells were incubated with 0.5 LRU/ml SDX in OGD for 1 h. Results: We found that after short-term OGD (1-3 h), the drug increased the expression of both GSTP1 and Nrf2 mRNA/protein in HUVECs (p < 0.05), as determined by real-time PCR and enzyme-linked immunosorbent assay (ELISA). SDX treatment also enhanced the nuclear accumulation of Nrf2 in HUVECs after 1 h of OGD (p < 0.05). Conclusions: SDX induces a rapid onset of the antioxidant response by up-regulating the expression of GSTP1 and Nrf2 in endothelial cells subjected to in vitro simulated ischemia.
Ferrocene‐amino acid ester‐uracil conjugates, derived from four amino acids (l‐alanine, glycine, β‐alanine and γ‐aminobutyric acid), were synthesized via the Cu(I)‐catalyzed azide‐alkyne cycloaddition as the key step. The new compounds were characterized spectroscopically and by single‐crystal X‐ray crystallography in the case of the derivatives of glycine (monoclinic, P21/c) and γ‐aminobutyric acid (orthorhombic, Pca21). Electrochemical measurements showed subtle influence of the compounds’ structure on the redox potential of the Fc/Fc+ couple. Among the four compounds tested for antimicrobial activity, the conjugate obtained from l‐alanine possessed weak antifungal activity against Candida guillermondii.
Sulodexide (SDX) is a mixture of highly purified glycosaminoglycans (GAGs), consisting of 80% fast-moving heparin (FMH) and 20% dermatan sulfate (DS). Recently it is becoming more widely used, not only in the treatment of chronic venous disease, but also many other vascular disorders. The efficacy of SDX in the treatment of peripheral arterial disease (PAD) or diabetic nephropathy has also been demonstrated. The way that SDX operates on the biology of vascular endothelial cells is not fully understood. It has anticoagulant, profibrinolytic and anti-aggregative properties. Moreover, it delivers substrates for the reconstruction of vascular endothelial glycocalyx and, at the same time, inhibits the activity of enzymes responsible for cleaving GAGs. Besides its effects on the glycocalyx, which is located on the surface of endothelium, part of a dose penetrates the endothelial cells and has an effect on the expression of multiple growth factors. It has been observed that SDX has protective, reparative, anti-inflammatory, anti-oxidant, anti-apoptotic and an anti-atherosclerotic influence on vascular endothelial cells. In this review article, each of these aspects of SDX's activity has been thoroughly discussed in the context of chronic venous disease. Special regard was dedicated to the increasing amount of reports about the high efficiency of SDX in the treatment of patients with CVD at various stages. Sulodexide has a wide therapeutic range in the treatment of vascular disorders. Further research is needed to explain the precise mechanism of action of this pleiotropic drug.
Hydra, as sit-and-wait predators with limited food selectivity, could serve as model organisms for the analysis of the effect of a particular dietary component on growth and reproduction. We investigated the effect of food quality and of diets enriched with palmitic (PAM) or α-linolenic acid (ALA) on the life history traits of two hydra species: Hydra oligactis and Hydra vulgaris. We tested the hypothesis that a diet enriched with polyunsaturated fatty acids (PUFA) can stimulate growth and reproduction in simple metazoans with a sit-and-wait type of predatory strategy. Our results revealed that a diet based on Artemia nauplii, which are not a natural food for freshwater hydra, stimulated growth, asexual reproduction, and survival in hydra. Artemia nauplii were characterized by the highest lipid content of all used food sources. The analysis of the fatty acid content of hydra indicated the domination the n-6 fatty acids over n-3 (eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA], and ALA). Arachidonic acid appeared to be the dominant PUFA in Hydra, irrespective of diet supplementation with palmitic acid or ALA. The dietary supplementation of ALA negatively affected the survival, asexual reproductive rate, and size of clonal offspring of H. oligactis and had no effect on the life history traits of H. vulgaris. Our results also suggest that the hydras are not able to efficiently convert ALA into other essential fatty acids, such as EPA and DHA. To our knowledge, this is the first report about the adverse effects of n-3 fatty acid supplementation in primitive metazoans such as hydra.
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