Posted by MM Amin, GF Asaad, RMA Salam, et al.
on 2014-03-11 18:53:37
As a nutritional supplement, coenzyme Q10 (CoQ10) was tested previously in several models of diabetes and/or insulin resistance (IR); however, its exact mechanisms have not been profoundly explicated. Hence, the objective of this work is to verify some of the possible mechanisms that underlie its therapeutic efficacy. Moreover, the study aimed to assess the potential modulatory effect of CoQ10 on the antidiabetic action of glimebiride. An insulin resistance/type 2 diabetic model was adopted, in which rats were fed high fat/high fructose diet (HFFD) for 6 weeks followed by a single sub-diabetogenic dose of streptozotocin (35 mg/kg, i.p.). At the end of the 7th week animals were treated with CoQ10 (20 mg/kg, p.o) and/or glimebiride (0.5 mg/kg, p.o) for 2 weeks. CoQ10 alone opposed the HFFD effect and increased the hepatic/muscular content/activity of tyrosine kinase (TK), phosphatidylinositol kinase (PI3K), and adiponectin receptors. Conversely, it decreased the content/activity of insulin receptor isoforms, myeloperoxidase and glucose transporters (GLUT4; 2). Besides, it lowered significantly the serum levels of glucose, insulin, fructosamine and HOMA index, improved the serum lipid panel and elevated the levels of glutathione, sRAGE and adiponectin. On the other hand, CoQ10 lowered the serum levels of malondialdehyde, visfatin, ALT and AST. Surprisingly, CoQ10 effect surpassed that of glimepiride in almost all the assessed parameters, except for glucose, fructosamine, TK, PI3K, and GLUT4. Combining CoQ10 with glimepiride enhanced the effect of the latter on the aforementioned parameters. Conclusion: These results provided a new insight into the possible mechanisms by which CoQ10 improves insulin sensitivity and adjusts type 2 diabetic disorder. These mechanisms involve modulation of insulin and adiponectin receptors, as well as TK, PI3K, glucose transporters, besides improving lipid profile, redox system, sRAGE, and adipocytokines. The study also points to the potential positive effect of CoQ10 as an adds- on to conventional antidiabetic therapies.
Posted by M Sochacka, J Giebu?towicz, M Remiszewska, et al.
on 2014-03-11 18:37:15
Selol is a novel organoselenium Se(+IV) compound. It reveals lower potential of toxicity than sodium selenite and does not exhibit mutagenic activity. Its antioxidant and anticancer properties including overcoming cancer cell resistance to standard therapy of the drug were proven. This is the first publication describing the influence of Selol 5% on the activity of blood antioxidant status in vivo.
Materials and methods
We investigated the influence of Selol 5% short-term (24 h) and long-term (28 days) administration on the activity of antioxidant enzymes, including the main selenoenzymes, in healthy mice plasma and erythrocytes. Plasma oxygen radical absorbance capacity value (ORAC) and the concentration of malonyldialdehyde (MDA) in plasma as a biomarker of oxidative stress as well as the value of selenium (Se) concentration in erythrocytes were shown.
A significant increase of the selenium dependent glutathione peroxidase (Se-GSHPx) activity in plasma and erythrocytes, plasma selenoprotein P concentration, ORAC values, and Se concentration were observed during long-term supplementation as well as after Selol 5% single-dose administration, with two distinct increases of activity a few hours after the beginning of the experiment and before its end. We found a decreased thioredoxin reductase (THRR) activity and an increased MDA level during Selol 5% long-term supplementation. Glutathione S-transferase activity (GST) remained unchanged.
Selol 5% supplementation in vivo affects the selenoenzymes activities as well as the antioxidant status of plasma and erythrocytes. Selol 5% is an inhibitor of thioredoxin reductase activity, which can be important in anticancer therapy.
Posted by 石金河, 户瑞丽, 杨亚勤, et al.
on 2014-02-28 00:39:59
Posted by A Ceriello, A Novials, E Ortega, et al.
on 2014-02-28 00:28:10
Background and aims
Hypoglycemia produces thrombosis activation, but little attention has been paid to the effects of hyperglycemia following recovery from hypoglycemia on thrombosis activation.
Methods and results
In both twenty-two healthy subjects and twenty-one matched persons with type 1 diabetes, recovery from a 2-h induced hypoglycemia was obtained by reaching normo-glycemia or hyperglycemia for another 2 h. After this, normal glycemia was maintained for the following 6 h. Hyperglycemia after hypoglycemia was also repeated with the concomitant infusion of vitamin C. In both controls and people with diabetes, the recovery with normo-glycemia was accompanied by a significant improvement of Von Willebrand factor (vWF), prothrombin fragment 1 + 2 (F1 + 2), thrombin–antithrombin III-complexes (TAT), P-selectin, plasminogen activator inhibitor-1 (PAI-1), nitrotyrosine and 8-iso-prostaglandin F2α (8-iso-PGF2α) (p < 0.01 vs hypoglycemia for all the parameters), all directly affected by hypoglycemia itself (p < 0.01 vs baseline for all the parameters). On the contrary, the recovery with hyperglycemia after hypoglycemia worsens all these parameters (p < 0.01 vs normoglycemia for all the parameters), an effect persisting even after the additional 6 h of normo-glycemia. The effect of hyperglycemia following hypoglycemia was partially counterbalanced when vitamin C was infused (p < 0.01 vs hyperglycemia alone for all the parameters), suggesting that hyperglycemia following hypoglycemia may activate thrombosis through the oxidative stress production.
This study shows that, in type 1 diabetes as well as in controls, the way in which recovery from hypoglycemia takes place could play an important role in favoring the activation of thrombosis and oxidative stress, widely recognized cardiovascular risk factors.
Posted by A Gendy, H El-Abhar, AR Mohsen.
on 2014-02-28 00:21:15
Abstract- Cilostazol is an antiplatelet that acts by inhibiting phosphodiesterase-3 and that was proven to be effective in models of ischemia/reperfusion (I/R) injury; however, its possible role in hepatic I/R remains indistinct, which is the aim of the current work. To fulfill this goal, rats were randomized into sham, I/R and cilostazol (60mg/kg, p.o) groups. The hepatic artery and portal vein to the left and median liver lobes were occluded for 30 min and then declamped for reperfusion to establish a model of segmental (70%) warm hepatic ischemia. Pretreatment of animals with cilostazol for two weeks prior to I/R insult significantly decreased serum alanine aminotransferase, and inhibited I/R-induced hepatocytes apoptotic death signified by inhibition of caspase-3. Moreover, cilostazol increased ATP content and lowered the level of lipid peroxidation assessed as malondialdehyde. The drug also elevated the nitric oxide content and decreased that of tumor necrosis factor-α, as well as the myeloperoxidase activity, a marker of neutrophil infiltration. Mechanistic studies revealed that cilostazol protected the liver and enhanced its proliferation ability, where it markedly increased the level of β-catenin and cyclin D1, but blocked the phosphorylation of GSK-3β at Ser9. In conclusion, cilostazol pre-administration protected hepatocytes against I/R insult by virtue of its antioxidant, anti-inflammatory, and antiapoptotic effects; besides, the drug increased hepatocytes proliferation by increasing the level of cyclin D1. It increased also the Wnt/ β-catenin pathway, which aid in its hepatoprotective action along with blocking the GSK-3β phosphorylation at the ser9, which had injurious role in this work.