Coffee, caffeine, chlorogenic acid, and the purinergic system

Coffee is a drink prepared from roasted coffee beans and is lauded for its aroma and flavour. It is the third most popular beverage in the world. This beverage is known by its stimulant effect associated with the presence of methylxanthines. Caffeine, a purine-like molecule (1,3,7 trymetylxantine), is the most important bioactive compound in coffee, among others such as chlorogenic acid (CGA), diterpenes, and trigonelline. CGA is a phenolic acid with biological properties as antioxidant, anti-inflammatory, neuroprotector, hypolipidemic, and hypoglicemic. Purinergic system plays a key role inneuromodulation and homeostasis. Extracellular ATP, other nucleotides and adenosine are signalling molecules that act through their specific receptors, namely purinoceptors, P1 for nucleosides and P2 for nucleotides. They regulate many pathological processes, since adenosine, for instance, can limit the damage caused by ATP in the excitotoxicity from the neuronal cells. The primary purpose of this review is to discuss the effects of coffee, caffeine, and CGA on the purinergic system. This review focuses on the relationship/interplay between coffee, caffeine, CGA, and adenosine, and their effects on ectonucleotidases activities as well as on the modulation of P1 and P2 receptors from central nervous system and also in peripheral tissue

Dietary supplementation of ginger and turmeric improves reproductive function in hypertensive male rats

AbstractGinger [Zingiber officinale Roscoe (Zingiberaceae)] and turmeric [Curcuma longa Linn (Zingiberaceae)] rhizomes have been reportedly used in folk medicine for the treatment of hypertension. However, the prevention of its complication such as male infertility remains unexplored. Hence, the aim of the present study was to investigate the preventive effects of ginger and turmeric rhizomes on some biomarkers of male reproductive function in L-NAME-induced hypertensive rats. Male Wistar rats were divided into seven groups (n=10): normotensive control rats; induced (L-NAME hypertensive) rats; hypertensive rats treated with atenolol (10mg/kg/day); normotensive and hypertensive rats treated with 4% supplementation of turmeric or ginger, respectively. After 14 days of pre-treatment, the animals were induced with hypertension by oral administration of L-NAME (40mg/kg/day). The results revealed significant decrease in serum total testosterone and epididymal sperm progressive motility without affecting sperm viability in hypertensive rats. Moreover, increased oxidative stress in the testes and epididymides of hypertensive rats was evidenced by significant decrease in total and non-protein thiol levels, glutathione S-transferase (GST) activity with concomitant increase in 2′,7′-dichlorofluorescein (DFCH) oxidation and thiobarbituric acid reactive substances (TBARS) production. Similarly, decreased testicular and epididymal NO level with concomitant elevation in arginase activity was observed in hypertensive rats. However, dietary supplementation with turmeric or ginger efficiently prevented these alterations in biomarkers of reproductive function in hypertensive rats. The inhibition of arginase activity and increase in NO and testosterone levels by both rhizomes could suggest possible mechanism of action for the prevention of male infertility in hypertension. Therefore, both rhizomes could be harnessed as functional foods to prevent hypertension-mediated male reproductive dysfunction

Crosstalk between the Purinergic and Immune Systems: Implications for the Glutathione Antioxidant System in Health and Disease

Glutathione (GSH) represents the major nonprotein thiol in cells and, alongside with glutathione-dependent enzymes such as glutathione reductase (GR), glutathione peroxidase (GPx), and glutathione S-transferase (GST), exerts several biological functions including the protection against free radicals and other essential metabolic reactions within the body. Disturbances in the homeostasis of this complex glutathione antioxidant system may damage cells and have been implicated with the development and progression of several human diseases. In this context, the immune and purinergic systems are also essential, since the dysregulation in both systems may also be correlated with numerous diseases. These two networks are closely related and control inflammatory responses, especially by the crosstalk of signaling molecules, receptors, and enzymes; thus, they can exacerbate or slow down the progression of diseases. Based on this background, we aimed to provide a general scenario of the purinergic and immune systems and the connection between both and the modulation of glutathione and glutathione-dependent enzyme expression and activity in the context of health and disease

Oral Administration of N-acetylcysteine Improves Biochemical Parameters in Diabetic Rats

To evaluate the effect of N-acetylcysteine (NAC), a potent ROS scavenger and thiol group supplier, on normoglycemic and diabetic rats, the animals received 50 or 200 mg/kg NAC by gavage daily for 45 days. The results showed a lack of uniformity in acetylcholinesterase activity among the four cerebral structures. While neither dose of NAC produced significant hypoglycemic activity, 50 mg/kg NAC partially reverted the weight loss of diabetics and was effective in restoring aminolevulinate dehydratase activity and non-protein thiol content in liver, and in diminishing serum protein carbonylation. The dose of 200 mg/kg NAC presented some negative effects per se in both the antioxidant and cholinergic systems. In conclusion, 50 mg/kg NAC produced an improvement in some parameters suggesting NAC as a possible drug in antioxidant therapies against diabetic state. However, future studies are necessary to investigate the better dose of this compound to counteract its undesirable effects

Effect of dietary supplementation of Padauk (Pterocarpus soyauxii) leaf on high fat diet/streptozotocin induced diabetes in rats’ brain and platelets

Background This study investigated the effects of Padauk leaf on brain malondialdehyde (MDA) content, acetylcholinesterase (AChE) activities, ectonucleotidases and adenosine deaminase (ADA) activities in the platelet of high fat diet and streptozotocin (STZ)-induced diabetic rats. Methods The animals were divided into six groups (n = 7): normal control rats; diabetic rats + high fat diet (HFD); diabetic rats + HFD + Metformin; diabetic rats + HFD + acarbose; diabetic rats + HFD + 10% Padauk leaf; normal rats + basal diet + 10% Padauk leaf. After 30 days of experiment comprising of acclimatization, dietary manipulation, pre-treatment with STZ and supplementation with Padauk leaf, the animals were sacrificed and the rats’ brain and blood were collected for subsequent analysis. Results The results demonstrated that the elevated MDA content and AChE activity in the diabetic rats were significantly reduced when compared with the control rats. Furthermore, the increased NTPDases, 5′-nucleotidase and ADA activities in the diabetic rats were significantly reduced when compared with the control rats. Conclusion This study demonstrated that Padauk leaf exhibited modulatory effects on purinergic and cholinergic enzymes involved in the prevention of platelet abnormality and consequent vascular complications in diabetic state

Cholinesterase Activities and Oxidative Stress in Cattle Experimentally Exposed to Nitrate/Nitrite in Cultivated Pasture with Different Fertilization Schemes

Background: Nitrate and nitrite poisoning is associated with pasture intake that has high nitrate levels and leads to acute methemoglobinemia. Pasture may accumulate nitrate under certain conditions, such as excessively fertilized soil or environmental conditions that enhance the N absorption (rain preceded by a period of drought). After ingestion of plants, this substrate reaches the rumen and, in physiological conditions, is reduced to nitrite and afterward to ammonia. The aim of this study was to evaluate changes in cholinesterase activities and oxidative stress caused by subclinical poisoning for nitrate and nitrite in cattle fed with Pennisetum glaucum in three different fertilization schemes.Materials, Methods & Results: In order to perform the experimental poisoning, the pasture was cultivated in three different paddocks: with nitrogen topdressing (urea; group 1), organic fertilizer (group 2) or without fertilizer (group 3; control). Nitrate accumulation in forage was evaluated by the diphenylamine test. After food fasting of 12 h, nine bovine were randomly allocated to one of the experimental groups and fed with fresh forage (ad libitum) from respective paddock. In different time points from beginning of pasture intake (0, 2, 4, 6 and 9 h) heart rate and respiratory frequency were assessed, as well as mucous membrane color and behavioral changes. Blood samples from jugular vein into vials with and without anticoagulant were collected. From blood samples, serum nitrite levels, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme activity were evaluated, as well as oxidative stress through the following parameters: levels of nitrate/nitrite (NOx ), thiobarbituric acid reactive substances (TBARS) and reactive oxygen species (ROS), beyond the antioxidant system by enzyme activity measurement of catalase (CAT) and superoxide dismutase (SOD). The diphenylamine test was positive to group 1 and 2, so that the pasture presented 3.16 mg/kg, 2.98 mg/kg and 1.67 mg/kg of nitrate for group 1, 2 and 3, respectively. In addition, cows from group 1 demonstrated increased (P < 0.05) nitrite levels in serum, compared to other groups, and greater heart rate after 9 h (P < 0.05). The AChE and BChE activity in group 1 showed significant increase (P < 0.05) at 4 and 6 h (AChE), and 4 and 9 h (BChE) compared to group 3. Also, NOx levels were lower at 6 and 9 h (P < 0.05) and at 9 h (P < 0.05) for animals of group 1 and 2, respectively, when compared to group 3. Furthermore, in the group 1 levels of ROS and TBARS were significantly higher (P < 0.05) after 2 and 4 h, and 6 and 9 h compared to other groups, respectively. The CAT activity increased significantly (P < 0.05) with 2 and 4 h of the experiment, but on the other hand, decreased at 6 and 9 h in group 1. Nevertheless, the animals from group 2 presented only a significant reduction in this enzyme activity at 9 h. Furthermore, SOD activity was reduced in animals of groups 1 (P < 0.05) at 4, 6 and 9 h, compared to other groups.Discussion: It was concluded that the nitrate and nitrite poisoning by pasture intake cultivated and fertilized with urea leads to increased levels of serum nitrite, as well as the cholinesterase activity and causes oxidative stress in cattle. It is conjectured that the cholinesterase activity and oxidative stress may assist in understanding the pathophysiology of changes caused by poisoning

The Protective Effects of an Adsorbent against Oxidative Stress in Quails Fed Aflatoxin-Contaminated Diet

Background: Contamination of crops with aflatoxin is considered a serious global threat to food safety, since potent carcinogenic, teratogenic, mutagenic and immunosuppressive effects of aflatoxins are well recognized. Recently, the use of adsorbents has been linked with protective effects against oxidative stress in several diseases. Thus, the aim of this study was to assess the occurrence of oxidative stress in quails (Coturnix coturnix) fed with aflatoxin-contaminated diet, as well as the protective effect of an adsorbent.Materials, Methods &amp; Results: Twenty-eight quails were divided into four groups (n = 7): diet without additives (control; the group A), diet and adsorbent containing aluminosilicates (the group B), aflatoxin-contaminated diet (200 ppb) (the group C), and aflatoxin-contaminated diet (200 ppb) and adsorbent containing aluminosilicates (the group D). The composition of the adsorbent containing aluminosilicates was 0.3% based on yeast cell wall, silymarin, and bentonite. The animals received feed and water ad libitum during 20 days. At the end of the experimental period, total blood was collected by cardiac puncture in tubes without anticoagulant to obtain serum (centrifuged at 3500 g during 10 min) for later determination of biochemical parameters. The liver was placed in a solution of Tris–HCl 10 mM, pH 7.4 for TBARS (Thiobarbituric acid reactive substances), ROS (Reactive oxygen species), SOD (Superoxide dismutase) and CAT (Catalase) analysis. The hepatic tissue was gently homogenized in a glass potter in specific buffer, homogenated, and centrifuged at 10.000 g at 4ºC for 10 min to yield a supernatant (S1) used for analyses. Homogenate aliquots were stored at -80°C until utilization. Fragments of liver and intestine (5 cm) were collected for histopathological analyses. Between days 15 to 20 of the experiment, group C quails showed clinical signs, such as apathy, creepy feathers and reduced feed intake. At day 20 of experiment, macroscopically, the liver of quails belonging to the group C showed greenish yellow color differently from the other groups. Microscopically, no alterations were observed in the liver of animals in groups A and B. Severe diffuse microvacuolar degeneration (hydropic) of hepatocytes and small foci of necrosis in the liver were observed in the group C, as observed in the group D, but in a more moderate degree to microvacuolar degeneration. Seric total protein, albumin, globulin and uric acid levels decreased in the group C and D. The levels of alanine aminotransferase (ALT) increased in the group C, and the treatment with adsorbent was able to avoid this increment. Seric and hepatic reactive oxygen species and TBARS increased in the group C, and the treatment with adsorbent reduced theses parameters in the group D. Catalase (CAT) activity decreased, while ALA-D increased in the group C. The treatment with adsorbent was able to prevent CAT activity decrease, but it did not prevent the increase in ALA-D activity.Discussion: Aflatoxins are considered one of the most important problems in poultry production causing high economic losses to producers. In this study, the use of adsorbent showed a protective effect to hepatic tissue, minimizing histopathological lesions, as well as by preventing lipid peroxidation and exacerbated production of free radicals. Based on this data, aflatoxin intoxication causes hepatic oxidative stress that contributes directly to disease pathogenesis, and the addition of an adsorbent containing 0.3% based on bentonite, yeast cell wall and silymarin may be considered a new approach to prevent cellular and hepatic damage caused by aflatoxins

Biochemical detection of E-ADA on Neospora caninum tachyzoites and the effects of a specific enzymatic inhibitor

Objective. This study aimed to investigate the presence and activity of the ecto adenosine deaminase (E-ADA) enzyme in tachyzoites of Neospora caninum (Nc-1 strain), as well as to assess the activity of a well-known E-ADA inhibitor, the deoxycoformycin. Materials and methods. The parasites were grown in cell culture, being subsequently separated in a pellet of tachyzoites, on which the E-ADA activity was tested using the concentrations 0 (control), 0.2, 0.4 and 0.8 mg mL-1. Results. The E-ADA showed high activity, progressively increasing its activity according to the enhancement of the protein concentration. The test was carried out with different concentrations of deoxycoformycin, showing that it was able to inhibit the E-ADA present on the free form of the parasite. Conclusions. Based on these results we conclude that the E-ADA is present on tachyzoites of N. caninum, and deoxycoformycin is able to inhibit this enzyme. In this sense, knowing the negative impact of N. caninum on reproductive issue in cattle (mainly abortion), might it is an alternative in order to deal with this parasitic infection. Key words: adenosine deaminase, deoxycoformycin, neosporosis (Source: CAB, MeSH)

Anthocyanins restore behavioral and biochemical changes caused by streptozotocin-induced sporadic dementia of Alzheimer's type

Aims The aim of this study was to analyze if the pre-administration of anthocyanin on memory and anxiety prevented the effects caused by intracerebroventricular streptozotocin (icv-STZ) administration-induced sporadic dementia of Alzheimer's type (SDAT) in rats. Moreover, we evaluated whether the levels of nitrite/nitrate (NOx), Na+,K+-ATPase, Ca2 +-ATPase and acethylcholinesterase (AChE) activities in the cerebral cortex (CC) and hippocampus (HC) are altered in this experimental SDAT. Main methods Male Wistar rats were divided in 4 different groups: control (CTRL), anthocyanin (ANT), streptozotocin (STZ) and streptozotocin + anthocyanin (STZ + ANT). After seven days of treatment with ANT (200 mg/kg; oral), the rats were icv-STZ injected (3 mg/kg), and four days later the behavior parameters were performed and the animals submitted to euthanasia. Key findings A memory deficit was found in the STZ group, but ANT treatment showed that it prevents this impairment of memory (P < 0.05). Our results showed a higher anxiety in the icv-STZ group, but treatment with ANT showed a per se effect and prevented the anxiogenic behavior induced by STZ. Our results reveal that the ANT treatment (100 μM) tested displaces the specific binding of [3H] flunitrazepam to the benzodiazepinic site of GABAA receptors. AChE, Ca+-ATPase activities and NOx levels were found to be increased in HC and CC in the STZ group, which was attenuated by ANT (P < 0.05). STZ decreased Na+,K+-ATPase activity and ANT was able to prevent these effects (P < 0.05). Significance In conclusion, these findings demonstrated that ANT is able to regulate ion pump activity and cholinergic neurotransmission, as well as being able to enhance memory and act as an anxiolytic compound in animals with SDAT