Purine Metabolism in Platelets and Heart Cells of Hyperlipidemic Rats.

PURPOSE: Hyperlipidemia, characterized by an increase in circulating lipid levels, doubles the chance of developing cardiovascular diseases. It prompts inflammation, immune activation, and oxidative stress in the bloodstream and organs of rats. Thus, we theorized that the metabolism of purines, an immunomodulatory mechanism, is altered in cells involved in the development of cardiovascular diseases. METHODS: Therefore, we induced acute hyperlipidemia in Wistar rats with Poloxamer-407 and euthanized the animals 36 h later. The leucocyte differential, the rate of purine metabolism on the surface of platelets and heart cells, and markers of oxidative stress in the heart tissue were evaluated. These parameters were also assessed in animals pretreated for 30 days with curcumin and/or rutin. RESULTS: Hyperlipidemia increased the hydrolyses of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) in platelets. In heart cells, the metabolism of ATP and adenosine (ADO) were increased, while ADP hydrolysis was reduced. Additionally, lipid damage and antioxidant defenses were increased in heart homogenates. Hyperlipidemic rats also exhibited a reduced percentage of eosinophils and lymphocytes. CONCLUSION: Together, these findings are indicative of an increased risk of developing cardiovascular diseases in hyperlipidemic rats. The pretreatments with antioxidants reverted some of the changes prompted by hyperlipidemia preventing detrimental changes in the cells and tissues. Graphical Abstract.

Hypercholesterolemia and Ecto-enzymes of Purinergic System: Effects of Paullinia cupana.

Hypercholesterolemia is a metabolic disorder characterized by high levels of low-density lipoprotein and blood cholesterol, causing inflammatory lesion. Purinergic signaling modulates the inflammatory and immune responses through adenine nucleotides and nucleoside. Guaraná has hypocholesterolemic and antiinflammatory properties. Considering that there are few studies demonstrating the effects of guaraná powder on the metabolism of adenine nucleotides, we investigated its effects on the activity of ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) and ecto-adenosine deaminase activity in lymphocytes of rats with diet-induced hypercholesterolemia. The rats were divided into hypercholesterolemic and normal diet groups. Each group was subdivided by treatment: saline, guaraná powder 12.5, 25, or 50 mg/kg/day and caffeine concentration equivalent to highest dose of guaraná, fed orally for 30 days. An increase in adenosine triphosphate hydrolysis was observed in the lymphocytes of rats with hypercholesterolemia and treated with 25 or 50 mg/kg/day when compared with the other groups. The hypercholesterolemic group treated with the highest concentration of guaraná powder showed decreased ecto-adenosine deaminase activity compared with the normal diet groups. Guaraná was able to reduce the total cholesterol and low-density lipoprotein cholesterol to basal levels in hypercholesterolemic rats. High concentrations of guaraná associated with a hypercholesterolemic diet are likely to have contributed to the reduction of the inflammatory process.

Cytoprotective and genoprotective effects of ß-glucans against aflatoxin B1-induced DNA damage in broiler chicken lymphocytes.

The polysaccharide ß-glucan presents beneficial effects on the immune system, although the mechanisms of the immunomodulatory effect remain poorly understood. The potential cytoprotective and genoprotective effects of ß-glucans were evaluated in broiler chicken lymphocytes exposed to increasing concentrations of aflatoxin B1 (AFB1) and/or ß-glucans. AFB1 significantly decreased cell viability at the concentrations of 10 and 20 µg/ml at 72 h of incubation (p<0.01 and p<0.001, respectively). Moreover, the AFB1 concentrations of 1, 10 and 20 µg/ml increased DNA fragmentation levels at 24 h (p<0.001). Conversely, lymphocyte death was prevented by ß-glucans at the concentrations of 1% and 10%, indicating a cytoprotective effect. Reactive oxygen species levels were increased in the cells treated with 20 µg/ml AFB1 at 24 h (p<0.05) and 10% ß-glucans with or without AFB1 at 24, 48 and 72 h of incubation (p<0.001). DNA damage increased by more than 100% in AFB1-treated lymphocytes when compared to control group. ß-glucans at 1% was able to fully revert the AFB1-induced lymphocyte DNA damage, indicating a genoprotective effect and maintaining DNA integrity. In conclusion, ß-glucans showed in vitro dose-dependent cytoprotective and genoprotective effects in broiler chicken lymphocytes exposed to AFB1.

Improved efficacy in the treatment of contact dermatitis in rats by a dermatological nanomedicine containing clobetasol propionate.

We developed a dermatological nanomedicine containing clobetasol propionate-loaded nanocapsules and evaluated its efficacy in a model of contact dermatitis after topical administration in rats. Hydrogels containing clobetasol propionate-loaded lipid-core nanocapsules or nanoemulsion (HG-CP-NC and HG-CP-NE, respectively) were prepared to evaluate the influence of the polymeric wall. They presented adequate pH values (5.50-6.50) and drug content (0.5 mg g(-1)) and their rheograms exhibited a non-Newtonian pseudoplastic behavior. The best in vitro drug release control was obtained for HG-CP-NC (1.03±0.11 µg cm(-2) h) compared to the HG-CP-NE (1.65±0.19 µg cm(-2) h) and the hydrogels containing nonencapsulated drug (HG-CP) (2.79±0.22 µg cm(-2) h). A significant increase in NTPDase activity was observed in lymphocytes for the group treated with 0.05% HG-CP-NC every other day compared to the group treated with 0.05% HG-CP every day using the in vivo model of contact dermatitis. The nanoencapsulation of clobetasol in nanocapsules led to a better control of the drug release from the semisolid nanomedicine and provided better in vivo dermatological efficacy.