Caffeine and high intensity exercise: Impact on purinergic and cholinergic signalling in lymphocytes and on cytokine levels.

This study evaluated the effects of caffeine in combination with high-intensity interval training (HIIT) on sensitivity to glucocorticoids and proliferation of lymphocytes, IL-6 and IL-10 levels and NTPDase, adenosine deaminase (ADA) and acetylcholinesterase (AChE) activity in rat lymphocytes. The animals were divided into groups: control, caffeine 4 mg/kg, caffeine 8 mg/kg, HIIT, HIIT plus caffeine 4 mg/kg and HIIT plus caffeine 8 mg/kg. The rats were trained three times a week for 6 weeks for a total workload 23% of body weight at the end of the experiment. Caffeine was administered orally 30 min before the training session. When lymphocytes were stimulated with phytohaemagglutinin no changes were observed in proliferative response between trained and sedentary animals; however, when caffeine was associated with HIIT an increase in T lymphocyte proliferation and in the sensitivity of lymphocytes to glucocorticoids occurred. ATP and ADP hydrolysis was decreased in the lymphocytes of the animals only trained and caffeine treatment prevented alterations in ATP hydrolysis. HIIT caused an increase in the ADA and AChE activity in lymphocytes and this effect was more pronounced in rats trained and supplemented with caffeine. The level of IL-6 was increased while the level of IL-10 was decreased in trained animals (HIIT) and caffeine was capable of preventing this exercise effect. Our findings suggest that caffeine ingestion attenuates, as least in part, the immune and inflammatory alterations following a prolonged HIIT protocol.

Protective effect of rosmarinic acid against oxidative stress biomarkers in liver and kidney of strepotozotocin-induced diabetic rats.

In the present study, we investigated the efficiency of rosmarinic acid (RA) in preventing the alteration of oxidative parameters in the liver and kidney of diabetic rats induced by streptozotocin (STZ). The animals were divided into six groups (n = 8): control, ethanol, RA 10 mg/kg, diabetic, diabetic/ethanol, and diabetic/RA 10 mg/kg. After 3 weeks of treatment, we found that TBARS levels in liver and kidney were significantly increased in the diabetic/saline group and the administration of RA prevented this increase in the liver and kidney (P < 0.05). Diabetes caused a significant decrease in the activity of superoxide dismutase (SOD) and catalase (CAT) in the diabetes/saline group (P < 0.05). However, the treatment with 10 mg/kg RA (antioxidant) prevented this alteration in SOD and CAT activity in the diabetic RA group (P < 0.05). In addition, RA reverses the decrease in ascorbic acid and non-protein-thiol (NPSH) levels in diabetic rats. The treatment with RA also prevented the decrease in the Delta-aminolevulinic acid dehydratase (ALA-D) activity in the liver and kidney of diabetic rats. Furthermore, RA did not have any effect on glycemic levels. These results indicate that RA effectively reduced the oxidative stress induced by STZ, suggesting that RA is a potential candidate for the prevention and treatment of pathological conditions in diabetic models.

Neuroprotective effect of quercetin in ectoenzymes and acetylcholinesterase activities in cerebral cortex synaptosomes of cadmium-exposed rats.

This study investigated the effect of quercetin on nucleoside triphosphate diphosphohydrolase (NTP-Dase), 50-nucleotidase, adenosine deaminase (ADA), and acetylcholinesterase (AChE) activities in synaptosomes from cerebral cortex of adult rats exposed to cadmium (Cd). Rats were exposed to Cd (2.5 mg/Kg) and quercetin (5, 25 or 50 mg/Kg) by gavage for 45 days. Rats were randomly divided into eight groups (n = 8-10): saline/ethanol, saline/Querc 5 mg/kg, saline/Querc 25 mg/kg, saline/Querc 50 mg/kg, Cd/ethanol, Cd/Querc 5 mg/kg, Cd/Querc 25 mg/kg, and Cd/Querc 50 mg/kg. Results demonstrated that AChE activity increased in the Cd/ethanol group when compared to saline/ethanol group. Treatment with quercetin prevented the increase in AChE activity when compared to Cd/ethanol group. Quercetin treatment prevented the cadmium-induced increase in NTPDase, 5-nucleotidase, and ADA activities in Cd/ethanol group when compared to saline/ethanol group. Our data showed that quercetin have a protector effect against Cd intoxication. This way, is a promising candidate among the flavonoids to be investigated as a therapeutic agent to attenuate neurological disorders associated with Cd intoxication.

Exercise training prevents ecto-nucleotidases alterations in platelets of hypertensive rats.

In this study, we investigated the effect of 6 weeks of swimming training on the ecto-nucleotidase activities and platelet aggregation from rats that developed hypertension in response to oral administration of L-NAME. The rats were divided into four groups: control (n = 10), exercise (n = 10), L-NAME (n = 10), and exercise L-NAME (n = 10). The animals were trained five times per week in an adapted swimming system for 60 min with a gradual increase of the workload up to 5 % of animal's body weight. The results showed an increase in ATP, ADP, AMP, and adenosine hydrolysis, indicating an augment in NTPDase (from 35.3 ± 8.1 to 53.0 ± 15.1 nmol Pi/min/mg protein for ATP; and from 21.7 ± 7.0 to 46.4 ± 15.6 nmol Pi/min/mg protein for ADP as substrate), ecto-5'-nucleotidase (from 8.0 ± 5.7 to 28.1 ± 6.9 nmol Pi/min/mg protein), and ADA (from 0.8 ± 0.5 to 3.9 ± 0.8 U/L) activities in platelets from L-NAME-treated rats when compared to other groups (p < 0.05). A significant augment on platelet aggregation in L-NAME group was also observed. Exercise training was efficient in preventing these alterations in the exercise L-NAME group, besides showing a significant hypotensive effect. In conclusion, our results clearly indicated a protector action of moderate intensity exercise on nucleotides and nucleoside hydrolysis and on platelet aggregation, which highlights the exercise training effect to avoid hypertension complications related to ecto-nucleotidase activities.

α-Tocopherol regulates ectonucleotidase activities in synaptosomes from rats fed a high-fat diet.

α-Tocopherol (α-Toc) is involved in various physiologic processes, which present antioxidant and neuroprotective properties. High-fat diets have an important role in neurodegenerative diseases and neurological disturbances. This study aimed to investigate the effects of treatment with α-Toc and the consumption of high-fat diets on ectonucleotidase activities in synaptosomes of cerebral cortex, hippocampus and striatum of rats. Animals were divided into four different groups, which received standard diet (control), high-fat saturated diet (HF), α-Toc and high-fat saturated diet plus α-Toc (α-Toc + HF). High-fat saturated diet was administered ad libitum and α-Toc by gavage using a dose of 50 mg·kg(-1). After 3 months of treatment, animals were submitted to euthanasia, and cerebral cortex, hippocampus and striatum were collected for biochemical assays. Results showed that adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP) hydrolysis in the cerebral cortex, hippocampus and striatum were decreased in HF in comparison to the other groups (P < 0·05). When rats that received HF were treated with α-Toc, the activity of the ectonucleotidases was similar to the control. ATP, ADP and AMP hydrolysis in the cerebral cortex, hippocampus and striatum were increased in the α-Toc group when compared with the other groups (P < 0·05). These findings demonstrated that the HF alters the purinergic signaling in the nervous system and that the treatment with α-Toc was capable of modulating the adenine nucleotide hydrolysis in this experimental condition.

Effects of resveratrol on biomarkers of oxidative stress and on the activity of delta aminolevulinic acid dehydratase in liver and kidney of streptozotocin-induced diabetic rats.

The present study investigated the effects of resveratrol (RV), a polyphenol with potent antioxidant properties, on oxidative stress parameters in liver and kidney, as well as on serum biochemical parameters of streptozotocin (STZ)-induced diabetic rats. Animals were divided into six groups (n = 8): control/saline; control/RV 10 mg/kg; control/RV 20 mg/kg; diabetic/saline; diabetic/RV10 mg/kg; diabetic/RV 20 mg/kg. After 30 days of treatment with resveratrol the animals were sacrificed and the liver, kidney and serum were used for experimental determinations. Results showed that TBARS levels were significantly increased in the diabetic/saline group and the administration of resveratrol prevented this increase in the diabetic/RV10 and diabetic/RV20 groups (P < 0.05). The activities of catalase (CAT), superoxide dismutase (SOD) and aminolevulinic acid dehydratase (δ-ALA-D) and the levels of non protein thiols (NPSH) and vitamin C presented a significant decrease in the diabetic/saline group when compared with the control/saline group (P < 0.05). The treatment with resveratrol was able to prevent these decrease improving the antioxidant defense of the diabetic/RV10 and diabetic/RV20 groups (P < 0.05). In addition, the elevation in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamiltransferase (γ-GT) activities as well as in levels of urea, creatinine, cholesterol and triglycerides observed in the diabetic/saline group were reverted to levels close to normal by the administration of resveratrol in the diabetic/RV10 and diabetic/RV20 groups (P < 0.05). These findings suggest that resveratrol could have a protector effect against hepatic and renal damage induced by oxidative stress in the diabetic state, which was evidenced by the capacity of this polyphenol to modulate the antioxidant defense and to decrease the lipid peroxidation in these tissues.