Superoxide dismutase 1 and glutathione peroxidase 1 are involved in the protective effect of sulodexide on vascular endothelial cells exposed to oxygen-glucose deprivation.

Sulodexide (SDX) is widely used in the treatment of both arterial and venous thrombotic disorders. In addition to its recognized antithrombotic action, SDX has endothelial protective potential, which is independent of the coagulation/fibrinolysis system. However, the detailed molecular mechanisms of the endothelioprotective action of the drug are still unresolved. The aim of the present study was to determine whether treatment with SDX at concentrations of 0.125-0.5 lipase releasing unit (LRU)/ml have on the expression and activity of antioxidant enzymes in ischemic endothelial cells and how these effects might be related to the antiapoptotic properties of SDX. In the present study, human umbilical vein endothelial cells (HUVECs) were subjected to ischemia-simulating conditions (combined oxygen and glucose deprivation, OGD) for 6h to determine the protective effects of SDX. SDX (0.25 and 0.5LRU/ml) in OGD significantly increased the cell viability and prevented mitochondrial depolarization in the HUVECs. Moreover, SDX protected the HUVECs against OGD-induced apoptosis. At concentrations of 0.25 and 0.5LRU/ml, the drug increased both superoxide dismutase 1 (SOD1) and glutathione peroxidase 1 (GPx1) mRNA/protein expression together with a significant attenuation of oxidative stress in ischemic HUVECs. Our findings also demonstrate that an increase in both SOD and GPx activity is involved in the protective effect of SDX on ischemic endothelial cells. Altogether, these results suggest that SDX has a positive effect on ischemia-induced endothelial damage because of its antioxidant and antiapoptotic properties.

The impact of family environment on the development of alcohol dependence.

BACKGROUND: Alcoholism is a family disease. Many studies confirm that a family history of alcoholism is associated with the development of later alcohol dependence. The aim of this study is to analyze the impact of family structure and relations between its members in the development of alcohol addiction in children grown up in these families. SUBJECTS AND METHODS: The research study was based on authors` anonymous questionnaire including questions referring to: family structure, parents' divorce, prevalence of alcoholism in the family, parents' attitude towards alcohol and parent-child relationships. The study group consisted of 125 people, 83 men and 42 women, aged from 22 to 68 participating in treatment programs for alcohol addiction. The control group consisted of 231 people, 136 men and 95 women, age from 17 to 65, with no history of alcoholism. RESULTS: The study group participants stated less frequently that they had been raised by both parents (78% vs 87%, p<0.05). In this group one of the parents significantly more frequently abused alcohol (43% vs 19%; p<0.05) or both parents abused alcohol (15% vs 1%; p<0.05). The participants also claimed to be more often punished for their failures, abused physically/verbally and could less often depend on their parents. CONCLUSIONS: Based on these results we concluded that patients addicted to alcohol were more often raised by a single parent, they were more likely to have alcohol-dependent parents and relationships with their parents were more often impaired.

Association of early drinking onset with subsequent alcohol abuse.

BACKGROUND: In the recent years the phenomenon of early alcohol initiation is observed. This problem is often underestimated, in spite of its numerous negative consequences SUBJECTS AND METHODS: The research study was based on authors` anonymous questionnaire including questions referring to: age of alcohol initiation, age of the first blackout after drinking alcohol, the place and circumstances of alcohol initiation and the reason of drinking alcohol for the first time. The study group consisted of 125 people, 83 men and 42 women, aged from 22 to 68 participating in treatment programs for alcohol addiction. RESULTS: In the study group it occurred before the age of 15 more often than in the control group (49% vs. 42%). The same correlation exists for the alcohol initiation before 12 years of age (13% vs. 8%) and is statistically significant (p<0.05). What's very alarming drinking alcohol for the first time took place for some of the respondents before the age of 10 and also significantly more often in the study group (6% vs. 2%, p<0.05). CONCLUSIONS: The obtained results allow to conclude that in patients addicted to alcohol the initiation took place earlier than in the study group (age 13-15 vs. 16-18). Also, very early alcohol initiation (<12 years) occurred more frequently in the study group (12.8% vs 8.2%). Based on our research, we confirmed that early drinking onset is associated with subsequent alcohol dependence.

Sulodexide up-regulates glutathione S-transferase P1 by enhancing Nrf2 expression and translocation in human umbilical vein endothelial cells injured by oxygen glucose deprivation.

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.

Alpha-Linolenic Acid, but Not Palmitic Acid, Negatively Impacts Survival, Asexual Reproductive Rate, and Clonal Offspring Size in Hydra oligactis.

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.