Increased Adenosine Deaminase Activity Research Articles

ОСОБЕННОСТИ МЕТАБОЛИЗМА ЭПИТЕЛИАЛЬНОЙ ОПУХОЛИ ПРИ ЕЁ МЕЗЕНХИМАЛЬНОМ ПЕРЕХОДЕ

The epithelial tumors of various localizations are capable of producing reactive oxygen species that stimulate their epithelial-mesenchymal transformation. For tumors of non-small cell lung cancer (NSCLC), gastric and intestinal adenocarcinomas (GIAC) their metabolic heterogeneity was established. By the results of analysis in morphologically homogeneous tumors of the same localization we detected clusters of tumors characterized by increased activity of xanthine oxidase, superoxide dismutase, decreased activity of glutathione peroxidase (negative relation with pathology (ρ = -0,465, p < 0,05)). Thus, glutathione peroxidase activity was minimal in the second GIAC cluster, 1.4-fold lower, and 1.8-fold lower in their first cluster than in NSCLC tumors of the corresponding clusters. In the second NSCLC cluster, it was 1.5-fold lower than in their first cluster. Against this background, superoxide dismutase activity in tumors of different localizations included in the second clusters, on the contrary, increased 2-fold in NSCLC and 1.7-fold in GIAC, respectively. It leads to increased production of hydrogen peroxide in the tumor. Increase of adenosine deaminase activity detected (positive strong correlation (Spearman rank correlation coefficient ρ = 0,805, p < 0.01)) may be accompanied by a decrease of adenosine levels and its regulatory effects preventing tumor aggressive properties. Correlation of enzymatic activity with pathology was established. In different localization tumors the possibility of metabolic stimulation of tumor epithelial-mesenchymal transformation was revealed.

Relationship between Adenosine Deaminase Activity in the Cerebral Cortex and the Stimulating Effect of Caffeine in Adult Wistar Rats of Different Ages.

The aim of this study was to test the hypothesis that the higher the activity of adenosinedeaminase (ADA) in the brain, the greater should be the motor activity of animals, and possibly the stronger the psychostimulant effect of caffeine. We studied the effect of caffeine (10 and 20 mg/kg) on the motor activity and ADA activity in the frontal cortex of the brain in 2- and 5-month-old rats with different levels of spontaneous motor activity. Total motor activity significantly decreased with age, which was accompanied by a decrease in ADA activity. Administration of caffeine in a dose of 10 mg/kg stimulated motor activity in both 2- and 5-month-old animals, while ADA activity decreased in 2-month-old rats and increased in 5-month-old animals. Administration of caffeine in a dose of 20 mg/kg did not change the motor activity, however, in 5-month-old animals it led to an even greater increase in ADA activity. Thus, the age-related decrease in motor activity can be due to a decrease in ADA activity. However, the effect of caffeine on motor activity is not directly related to ADA activity in the cerebral cortex.

The features of enzymes activity to nucleoside and antioxidant systems in solid tumors

Background. Solid tumors can create their aggressive properties. There are characterized by the invasion and metastatic activity, the resistance of the tumor clone to apoptosis. These pathways triggering may be realized both by 2-deoxy-D-ribose and its phosphorylated form (2-d-D-Rib-1-P), and by hydrogen peroxide.Aim. To investigate the peculiarities of enzymes activity to nucleoside metabolism and antioxidant system in epithelial tumors of different localization.Materials and methods. The features of the thymidine phosphorylase, adenosine deaminase, superoxide dismutase (SOD) and glutathione peroxidase (GPO) activity were studied in tumor homogenates. The visually no transformed tissues of the surgical resection edges were used as a control. Enzymes activity was determined by spectrophotometrical and morphological features were examined by the immunohistochemical methods in tissues of non-small cell lung cancer (NSCLC), samples of gastric and colon carcinomas (GCC).Results. Thymidine phosphorylase activity and adenosine deaminase activity in various malignant tumors were increased in comparison to the control. Respectively, thymidine phosphorylase activity was higher than by 1.8 times (p= 0.002 for NSCLC,p= 0.001 for GCC). An increase of adenosine deaminase activity was revealed both in tissues of NSCLC (more than 1.7 times) and in GCC (by 1.9 times,p= 0.001). No significant changes in SOD activity were detected in the tumors. GPO activity tended to decrease by an average of 1.3 times (p= 0.01 for NSCLC,p= 0.02 for GCC). A cluster analysis of the enzymatic activity features of the studied NSCLC tumors, as well as GCC, revealed their metabolic heterogeneity. According to its results, tumors of different localization were distinguished into 2 clusters. Common feature to their second clusters was an increase the SOD activity. It was accompanied by increase of thymidine phosphorylase activity (p= 0.045 for NSCLC,p= 0.049 for GCC). Therefore, both hydrogen peroxide and 2-d-D-Rib-1-P could be formed in them more intensively. It is important to note that morphological indicators of tumor aggression (decreased or lost expression of cell-cell adhesion marker, expression of mesenchymal markers, active angiogenesis) were detected more frequently in these subgroups.Conclusion. The obtained results reveal that individual features of the enzymes activity in epithelial tumors may be available source of 2-d-D-Rib-1-P and hydrogen peroxide generation in human cancer cells. In the case of individual higher tumor activity of thymidine phosphorylase and SOD and low GPO activity the metabolic stimulation of tumor progression may be occur.

Neurotoxicity of anthracene and benz[a]anthracene involves oxidative stress-induced neuronal damage, cholinergic dysfunction and disruption of monoaminergic and purinergic enzymes.

In this study, the modulatory effects of anthracene (ANT) and benz[a]anthracene (BEN) on biochemical markers associated with neurodegeneration were assessed in mouse hippocampal neuronal cells (HT-22). Neuronal cells were cultured and exposed to ANT and BEN (25-125µM) for 5days, and the cell viability was determined via MTT assay. Morphological characteristics of the cells were assessed using a compound microscope. Biochemical parameters such as acetylcholinesterase (AChE), monoamine oxidase (MAO) and adenosine deaminase (ADA) activities as well as oxidative stress biomarkers (catalase [CAT], glutathione -S- transferase [GST] activities and Glutathione [GSH] levels) and nitric oxide [NO] levels were assessed after cells were treated with ANT and BEN for two days. The results showed that cell viability reduced with an increase in exposure time. After the fifth day of treatment, BEN and ANT (125µM) reduced percentage viability to 41 and 38.1%, respectively. Light micrographs showed shrinkage of cells, neuronal injury and cell death in cells treated with higher concentrations of BEN and ANT (50 and 125µM). Furthermore, AChE and MAO activities reduced significantly after treatment for 48h with ANT and BEN. A significant decrease in CAT and GST activities and low GSH levels were observed after treatment with BEN and ANT. However, both polycyclic aromatic hydrocarbons caused a significant increase in ADA activity and NO levels. These results suggest that ANT and BEN may induce neurodegeneration in neuronal cells via oxidative stress-induced-neuronal injury, disruption of cholinergic, monoaminergic and purinergic transmission, and increased nitric oxide levels.

Adenosine deaminase gene variant in diabetes and obesity.

Personal medicine is a new notion for individualizing treatment in the future. Studying pathogenic markers including genetic variants would be beneficial in better diagnosis and management of complex diseases such as diabetes and obesity. Adenosine deaminase (ADA) is a purine metabolic enzyme and modulates insulin activity in various tissues through several different mechanisms. Increased ADA activity is associated with decreased glucose uptake. A significant increase in serum deaminase activity has been reported in patients with T2DM and obesity. ADA gene polymorphisms seem to affect ADA enzymatic activity and a polymorphism at the position 4223 in the first intron of ADA gene (ADA 4223 A/C) has been previously associated with obesity. The aim of this study was to explore ADA gene 4223 A/C polymorphism and its association with obesity in patients with Type 2 diabetes. Obese patients (N = 133: 64 diabetic +69 non-diabetic) with BMI ≥ 30 and subjects with BMI < 30 (N = 152: 83 diabetics +69 non-diabetic) were recruited into a case-control association study. Blood samples were collected and after DNA extraction, the allele and genotype frequency for ADA gene polymorphism was determined using PCR-RFLP technique. We observed a significant increase for the frequency of AA+CA genotype in non-obese patients with diabetes compared to obese patients with diabetes (P = 0.04, OR = 2.1, 95%CI; 0.93-4.9). The higher frequency of AA+CA genotype in none obese diabetes individuals and lower frequency of this genotype in obese diabetes subjects indicates an important role for ADA gene polymorphism in diabetes subjects without obesity.

Quercetin enhances sexual behavior and improves ectonucleotidases activity in the hypothalamus of rats treated with cyclosporine.

In order to confirm the erectile potential of Quercetin (Q) in cyclosporine-induced hypertensive rats, this research assesses the influence of Q on the ectonucleotidases and adenosine deaminase (ADA) in the brains of rats. Male Wistar rats (200 g-250 g) were divided into five groups at random: Normal control (CTRL), cyclosporine-induced hypertensive rats (25 mgkgday-1 ) (HT) group, positive control (Sildenafil [SIL], 5 mgkgday-1 ), Quercetin 25 mgkgday-1 (25 Q), and Quercetin 50 mgkgday-1 (50 Q). Aside from standard diet-fed male rats; cyclosporine was given i.p for the period of 30days as well as Q orally while the female rats were only given a standard diet. The animals were subjected to sexual activity (copulation) after which the male rat hypothalamus was dissected for biochemical examination (E-NTPDase activities, ecto-5'-nucleotidase as well as ADA and also levels of nitric oxide [NO]). We observed that Q enhanced copulatory behavior as evident in mounting, intromission, ejaculation numbers, and latencies. A substantial (p<.05) increase in the activity of E-NTPDase (ATP and ADP as substrate) without any notable difference in the action of ecto-5' nucleotidase was facilitated by cyclosporine-induction when compared to the CTRL. The 50mg/kg, however, had the highest reversal effect in accordance with dose manner. Also, cyclosporine increased ADA activity with a concomitant reduction of NO level while both doses of Q down-regulated ADA activity and, increased NO levels. Enhanced sexual behavior, modulation of ectonucleotidases as well as ADA activity and increased NO levels suggest that Q-rich plant foods may be promising sources of dietary phytonutrients for erectile dysfunction (ED) management. PRACTICAL APPLICATIONS: Behavioral and biochemical assays evaluated showed that Q significantly enhanced sexual behavior as well as improved ATP bioavailability in cyclosporine-induced erectile dysfunctional rats. The modulatory effects of Q on ectonucleotidases, along with its ability to minimize adenosine deaminase activity and increase nitric oxide levels, indicate that Q-rich plants and/or plant foods may be promising sources of dietary phytonutrients for erectile dysfunction management.

Function of Serum Adenosine Deaminase as an Indicator of Immune Status in HIV Patients treated with Combination Antiretroviral Therapy

Acquired immunodeficiency syndrome (AIDS) is one of the greatest public health and social problems threatening the human race. The trend of annual AIDS deaths is showing a steady decline since the implementation of the free Anti-Retroviral Therapy (ART) program in India (2004). HIV infection is characterized by replication of virus by abnormal non specific immune activation and persistent inflammation. Adenosine deaminase (ADA) has a cytokine-like co-stimulatory role in T cell proliferation which is independent of catalytic activity. Therefore, we decided to study the role of ADA as an indicator of immune status in HIV patients treated with combination antiretroviral therapy (cART). Adenosine deaminase activity (ADA) in HIV patients was estimated before and after 3 months interval of antiretroviral therapy (ART) up to 9 months. The study included 150 HIV positive patients between age group of 20-50 years from ICTC (Integrated Counseling and Testing Centre) and ART centre. Venous blood samples were collected in plain bulb to estimate serum ADA activity before and after 3 months interval upto 9 months of ART. Serum ADA activity was estimated using colorimetric method of Giusti and Galanti. Activity of serum ADA was significantly raised before and after 3 months interval of ART with decrease in CD4 cell count. After 6 months, increased ADA activity started declining and comes to near normal after 9 months of ART (p&lt;0.001). Elevated serum adenosine deaminase activity in HIV patients is an indicator of T-cell activation. Serum ADA activity along with other markers can be used as a prognostic marker to monitor response to antiretroviral therapy and immunocompetence in HIV patients.

Study of Serum Adenosine Deaminase Level in Type 2 Diabetes Mellitus and its Correlation with Glycemic Control

Diabetes mellitus is a cluster of abnormal metabolic disorder having common features of hyperglycaemia with a state of increased free radical activity. Chronic hyperglycemic status favours auto-oxidation and the formation of advanced glycation end products. Adenosine deaminase (ADA) is considered as a good marker of cell mediated immunity. Increased ADA activity in diabetic individuals could be due to altered insulin related T-lymphocyte function. Hyperglycaemia is associated with increased level of (ADA), which is one of the factor which leads to increase oxidative stress level by generatingthe reactve oxygen species (ROS) leading to insulin resistance. In our study, ADA level was significantly high in controlled diabetes mellitus type 2 (group II with HbA1c &lt; 7) and was much higher in uncontrolled diabetics (group III with HbA1c &gt; 7) compared to healthy controls (group I). The present study was aimed to find the level of Serum (ADA) among the patients with type 2 diabetes mellitus through a case control study and correlation of Adenosine deaminase with glycemic control (HbA1c). Comparison of the parameters fasting plasma glucose (FPG), post prandial plasma glucose (PPPG) HbA1c, and ADA between the 3 groups were done using Student t test and was statistically significant. Pearson’s coefficient correlation was done between ADA and HbA1c and a positive correlaion was seen that was also statistically significant. This indicates that ADA ses with the extent of severity of type 2 diabetes. Positive correlation of ADA with HbA1c provides the information that ADA can be considered to reflect the glycemic status of the individual.

Untargeted Metabolomic Fingerprinting As a Potential Tool in the Diagnostic Evaluation of Diamond Blackfan Anemia

Background: Diamond-Blackfan anemia (DBA) is a rare inherited bone marrow failure syndrome (IBMFS) marked by erythroid hypoplasia, reticulocytopenia and macrocytosis, and associated with congenital malformations and an increased risk of developing malignancies. From a clinical and molecular perspective this disease is highly heterogeneous, and no clear genotype-phenotype correlations can be found. Since the majority of molecular defects have been found in ribosomal protein (RP) genes, DBA is regarded a "ribosomopathy". While the molecular basis has been studied intensively, the pathophysiology of DBA is still not fully understood. One of the major unresolved issues is how RP gene mutations result in the specific erythroid defect seen in DBA, with macrocytic erythrocytes and increased adenosine deaminase activity. In addition, the highly heterogeneous and variable clinical presentation and disease course, even in patients with similar molecular defects, remains enigmatic. Hence, in order to investigate the cellular defect, and increase our understanding of disease pathophysiology and clinical heterogeneity, novel tools are needed. In this study, we explore the potential of untargeted metabolomics on dried blood spots and report for the first time a metabolic fingerprint for DBA. Aims: Defining a metabolic signature for DBA in order to: 1. Increase our understanding of cellular determinants of impaired ribosome biogenesis, and 2. Extend the toolbox for diagnostic evaluation. Methods: Untargeted metabolic profiling was performed on DBS samples obtained from 18 DBA patients and 45 healthy controls using direct infusion high resolution mass spectrometry following a previously established approach1. Statistical analysis was performed in MetaboAnalyst and predictive modeling was executed within R-software. Results: In total, 1917 unique metabolite features were identified in DBS samples from patients and controls. Multivariate analysis yielded distinct metabolic profiles, reflected by natural separation detected by principal component analysis (Figure 1A), and emphasized by clear distinction with partial least square discriminant analysis (Figure 1B). This 'metabolic fingerprint' was incorporated into a machine learning algorithm, and subsequently a binary classification (or prediction) model was constructed by randomly dividing patient and controls into 'training' (32 HC, 13 DBA) or 'test' set (13 HC, 5 DBA). Accurate class assignment was achieved for all patients and controls in the training set (Figure 1C). Prominent metabolites in the fingerprint and classification algorithm were a.o. menadione (a vitamin K precursor), 4-hydroxyproline (collagen component) and methylmalonylcarnitine (an acylcarnitine). In addition a large number of interesting metabolites were identified that could provide novel starting points for studying/understanding downstream effects of RP defects in DBA and therapeutic mechanisms (Figure 1D). Conclusion: In this study we performed untargeted metabolomics on dried blood spots from a substantial cohort of DBA patients and report for the first time a metabolic fingerprint of this disease. By incorporating this fingerprint in a machine learning algorithm we underlined the diagnostic potential of this approach. Moreover, the metabolites identified in this fingerprint, provide promising starting points for further studies to increase our insights in disease pathophysiology, including the mechanism involved in elevated eADA activity, as well as the development of new therapeutic strategies.

Adenosine Deaminase as a Biomarker of Tenofovir Mediated Inflammation in Naïve HIV Patients.

Plasma levels of adenosine deaminase (ADA), an enzyme that deaminates adenosine to inosine, are increased during inflammation. An increase in ADA activity occurs with lower human immunodeficiency virus (HIV) viral load and higher CD4+ T cell counts. We aimed to investigate the role of plasma ADA as a biomarker of inflammation in treatment-naïve HIV patients who received tenofovir or another nucleoside analog for comparison. Ninety-two treatment-naïve patients were included in the study and grouped by treatment, i.e., tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) or Triumeq. ADA activity was measured in plasma and cytokines were analyzed by MILLIPLEX® MAP-Luminex® Technology. Plasma concentration of monocytes and neutrophils was measured at 0, 3, and 12 months post-treatment. Treatment-naïve HIV patients had increased ADA concentrations (over 15 U/L) that decreased after treatment with TAF and Triumeq, though this did not occur in TDF-treated patients. However, all groups exhibited a pro-inflammatory systemic profile at 12 months of treatment. Plasma GM-CSF levels decreased after 12 months of treatment in the TDF group, with a concomitant decrease in blood monocyte count, and a negative correlation with ADA values was found. In conclusion, ADA levels may be modulated by antiretroviral therapy in HIV patients, possibly affecting inflammatory status.

Tea tree oil attenuates cerebral damage in silver catfish (Rhamdia quelen) fed with an aflatoxin-contaminated diet

Aflatoxins are fungal metabolites that contaminate foods and feeds, causing adverse health effects in humans and animals. From an economic standpoint, aflatoxins represent one of the most severe problems for the livestock and feed industries. Currently, natural supplements are used to prevent various fungal infections in farmed fish. The aim of the present study was to determine whether dietary supplementation with tea tree oil (TTO: Melaleuca alternifolia) would prevent or minimize the effects of aflatoxin (AFB) on silver catfish (Rhamdia quelen). Four treatments were tested: control (without AFB);AFB (fish fed with a mycotoxin-contaminated diet – 1893 μg/kg of AFB1 and 52.2 μg/ kg AFB2); TTO (fish fed with a control diet +1 mL/kg of TTO), and TTO + AFB (fish fed with a mycotoxin contaminated diet - 2324 μg/kg of AFB1 and 43.5 μg/kg AFB2 + 1 mL/kg of TTO). Treatments were tested in three replications and were analyzed at days 5 and 10 of dietary intake. Increased activities of nucleoside triphosphate diphosphohydrolase (NTPDase) using ADP as substrate and adenosine deaminase (ADA) were observed after 5 day-feeding with AFB1 diet. Feed contaminated with AFB1 caused an inhibition of acetylcholinesterase (AChE) activity. Aflatoxicosis caused severe gliosis and subarachnoid edema. The addition of TTO in AFB1-contaminated feed prevented the inhibition of AChE activity and increased ADA activity. TTO supplementation increased p2y11 receptor expression, most likely in an attempt to deal with inflammation caused by aflatoxicosis. TTO treatment ameliorated aflatoxin-associated brain tissue damage. These findings suggest that TTO supplementation reduces the effects of aflatoxicosis in silver catfish brain tissue because it prevents most changes caused by AFB1-contaminated diet. Overall, the results obtained in the present study suggest that TTO could be used as an aflatoxin-detoxifying agent in fish.

BDNF is obverse to oxidative stress (adenosine deaminase and nitric oxide) in type II diabetes mellitus

The relational analysis of adenosine deaminase (ADA), nitric oxide (NO), BDNF (brain-derived neurotrophic factor), and TP (total protein) is accomplished by comparing these parameters with glucose levels of healthy and type II diabetes mellitus people. Type 2 diabetes (T2DM) is associated with impairment in many domains of cognitive function which may result from reduced BDNF. ADA is an important enzyme that plays a relevant role in purine and DNA metabolism, immune responses, and peptidase activity and for modulating the bioactivity of insulin. Nitric oxide is associated with loss of normal cellular function and increases the generation of nitric oxide synthetase products like nitroxyl (NO-), peroxynitrite (OONO-), and S-nitrosothiol (RSNO). In our study, a group of one hundred adult patients of either sex who had a history of not less than 6 years of diabetes mellitus and an equal number of healthy non-diabetics was selected as controls, respectively. The results of the parameters were analyzed using the SISA software and the correlation between the parameters was retrieved and represented graphically. A significant increase in adenosine deaminase activity and nitric oxide levels was observed in diabetic subjects when compared with that in controls. A significant decrease in total protein concentration and BDNF was observed in diabetic subjects when compared with that in controls. The results suggest that the increase in the glucose level has contributed to an increase in the inflammation factor ADA and oxidative stress factor NO and decrease in the total proteins especially BDNF, a neuron sentinel.

Is adenosine deaminase level a predictive biochemical marker of type II diabetes mellitus in obese Indian subjects

Objective: To evaluate serum Adenosine Deaminase (ADA) levels in obese and non obese Type II Diabetes Mellitus (T2DM) and compare it with healthy controls (obese and non obese). Materials and Methods: Total 100 subjects were included in the study. Fasting blood sugar (FBS) and ADA activity along with other routine biochemical parameters were determined in their serum. Based on their BMI and FBS level study subjects were divided into four groups: Control, Obese, Non obese T2DM and Obese T2DM.  Results: ADA activity was significantly increased (P Conclusion: In this study we observed an increased ADA activity in obesity and T2DM. A close relation may be present between insulin resistance produced in obese subjects and diabetics. Therefore ADA could therefore be used in routine lab investigations, especially in obese patients as a predictive marker for assessing the development of insulin resistance and hence diabetes. Keywords: Diabesity, ADA, Obesity, Insulin resistance, Fasting blood sugar.

Post-thyroidectomy hypothyroidism increases the expression and activity of ectonucleotidases in platelets: Possible involvement of reactive oxygen species

Signaling mediated by purines is a widespread mechanism of cell–cell communication related to vasomotor responses and the control of platelet function in the vascular system. However, little is known about the involvement of this signaling as well as the role of reactive oxygen species (ROS) in the development of hypothyroidism. Therefore, the present study investigates changes in the purinergic system, including enzyme activities and expression in platelets, and oxidative profiles in patients with post-thyroidectomy hypothyroidism. The nucleoside triphosphate diphosphohydrolase 1 (NTPDase/CD39) expression in patients increased by 40%, and the adenosine triphosphate (ATP) or adenosine diphosphate (ADP) hydrolyzing activity increased by 82% and 70%, respectively. The activities of ecto-5´-nucleotidase and adenosine deaminase (ADA) also significantly enhanced (39% and 52%, respectively), which correlates with a 45% decrease in adenosine concentration. Furthermore, these patients demonstrated an increased production of ROS (42%), thiobarbituric acid reactive substances (TBARS) (115%), carbonyl protein (30%) and a decreased glutathione S-transferase (GST) activity (20%). This study demonstrates that hypothyroidism interferes with adenine nucleoside and nucleotide hydrolysis and this is correlated with oxidative stress, which might be responsible for the increase in ADA activity. This increase causes rapid adenosine deamination, which can generate a decrease in their concentration in the systemic circulation, which can be associated with the development of vascular complications.

Involvement of cholinergic and adenosinergic systems on the branchial immune response of experimentally infected silver catfish with Streptococcus agalactiae

It has been recognized that the cholinergic and adenosinergic systems have an essential role in immune and inflammatory responses during bacterial fish pathogens, such as the enzymes acetylcholinesterase (AChE) and adenosine deaminase (ADA), which are responsible for catalysis of the anti-inflammatory molecules acetylcholine (ACh) and adenosine (Ado) respectively. Thus, the aim of this study was to investigate the involvement of the cholinergic and adenosinergic systems on the immune response and inflammatory process in gills of experimentally infected Rhamdia quelen with Streptococcus agalactiae. Acetylcholinesterase activity decreased, while ACh levels increased in gills of infected animals compared to uninfected animals. On the other hand, a significant increase in ADA activity with a concomitant decrease in Ado levels was observed in infected animals compared to uninfected animals. Based on this evidence, we concluded that infection by S.agalactiae in silver catfish alters the cholinergic and adenosinergic systems, suggesting the involvement of AChE and ADA activities on immune and inflammatory responses, regulating the ACh and Ado levels. In summary, the downregulation of AChE activity exerts an anti-inflammatory profile in an attempt to reduce or prevent the tissue damage, while the upregulation of ADA activity exerts a pro-inflammatory profile, contributing to disease pathophysiology.

Diphenyl Diselenide Reduces Oxidative Stress and Toxicity Caused by HSV-2 Infection in Mice.

Herpes simplex viruses can cause uncommon systemic complications as acute liver failure (ALT) or urinary tract dysfunctions. Diphenyl diselenide, (PhSe)2 , a classical studied organic selenium compound, has a novel antiviral action against HSV-2 infection and well-known antioxidant and anti-inflammatory properties. This study aimed to investigate if (PhSe)2 reduces oxidative stress and systemic toxicity caused by HSV-2 infection in mice. Adult BALB/c mice were pre-treated with (PhSe)2 (5 mg kg-1 /day, intragastric, i.g.) during 5 days; at day 6 mice were infected with HSV-2 (10 μl-105 PFU/mL-1 ) and post-treated with (PhSe)2 for more 5 days. At day 11, they were killed and samples of liver and kidney were obtained to determine: reactive species (RS); malondialdehyde (MDA), and non-protein thiols (NPSH) levels; the activities of antioxidant enzymes, superoxide dismutase (SOD), and catalase (CAT). The activities of adenosine deaminase (ADA), Na+ /K+ -ATPase (liver and kidney); alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the levels of urea (plasma) were determined as markers of hepatic and renal toxicity. The results revealed that (PhSe)2 treatment was effective against the increase of renal and hepatic oxidative stress in infected mice and also normalized hepatic and renal ADA activity. It recovered the activity of Na+ /K+ - and was not effective against the increase in urea levels in infected mice. Different from (PhSe)2 , acyclovir (positive control), caused an increase in ADA activity and a decrease in hepatic CAT activity. Considering the interest of alternative therapies to treat HSV-2 infections and secondary complications, (PhSe)2 become a notable candidate. J. Cell. Biochem. 118: 1028-1037, 2017. © 2016 Wiley Periodicals, Inc.

Protective effect of gallic acid and Syzygium cumini extract against oxidative stress-induced cellular injury in human lymphocytes

Context: Syzygium cumini (Myrtaceae) presents antioxidant, anti-inflammatory, hypoglycemic and antibacterial effects; however, the cellular and molecular mechanisms of action in the immune system are not yet completely elucidated. Objective: This study evaluates the in vitro effect of gallic acid and aqueous S. cumini leaf extract (ASc) on adenosine deaminase (ADA) and dipeptidyl peptidase IV (DPP-IV) activities, cell viability and oxidative stress parameters in lymphocytes exposed to 2, 2′-azobis-2-amidinopropane dihydrochloride (AAPH). Materials and methods: Lymphocytes were incubated with ASc (100 and 500 µg/ml) and gallic acid (50 and 200 µM) at 37 °C for 30 min followed by incubation with AAPH (1 mM) at 37 °C for 2 h. After the incubation time, the lymphocytes were used for determinations of ADA, DPP-IV and lactate dehydrogenase (LDH) activities, lipid peroxidation, protein thiol (P-SH) group levels and cellular viability by colorimetric methods. Results: (i) HPLC fingerprinting of ASc revealed the presence of catechin, epicatechin, rutin, quercitrin, isoquercitrin, quercetin, kaempferol and chlorogenic, caffeic, gallic and ellagic acids; (ii) for the first time, ASc reduced the AAPH-induced increase in ADA activity, but no effect was observed on DPP-IV activity; (iii) ASc increased P-SH groups and cellular viability and decreased LDH activity, but was not able to reduce the AAPH-induced lipid peroxidation; (iv) gallic acid showed less protective effects than ASc. Discussion and conclusion: ASc affects the purinergic system and may modulate adenosine levels, indicating that the extract of this plant exhibits immunomodulatory properties. ASc also may potentially prevent the cellular injury induced by oxidative stress, highlighting its cytoprotective effects.

Dietary Modulation of Thymic Enzymes

Malnutrition is a complex syndrome caused by an inadequate intake of energy, protein, minerals and vitamins which affects the immune system. Nutritional imbalances, present in children with energy-protein malnutrition and infections, make defining the specific effects of each of them on the thymus difficult. For this reason, it is necessary to design an experimental model in animals that could define a single variable. As the thymus atrophy described in humans is similar to that observed in murines, a rat experimental model makes the extrapolation to man possible. Some authors suggest that the activity of Adenosine Deaminase (ADA) and Purine Nucleoside Phosphorylase (PNP)--involved in purine metabolism--have an influence on T lymphocyte development and the immune system, due to intracellular accumulation of toxic levels of deoxynucleotides. Studies in our group, performed in an experimental model on Wistar growing rats, have demonstrated that protein deficiency or imbalance in the profile of essential amino acids in the diet, produce loss of thymus weight, reduction in the number of thymocytes, a diminished proportion of T cells presenting the W3/13 antigenic determinant and DNA content with concomitant increase in cell size, and the proportion of immature T cells and activity of ADA and PNP, without modifying the activity of 5´Nucleotidase in the thymus. It is important to point out that there were neither differences in energy intake between experimental groups and their controls, nor clinical symptoms of deficiency of other nutrients. The increase in these thymic enzyme activities was an alternative mechanism to avoid the accumulation of high levels of deoxynucleotides, which would be toxic for T lymphocytes. On the other hand, the administration of a recovery diet, with a high amount of high quality protein, was able to reverse the mentioned effects. The quick reply of Adenosine Deaminase to nutritional disorders and the following nutritional recovery, points out to this determination as a potential functional marker of nutritional status. Some authors have demonstrated an increase in ADA activity, in serum and other biological fluids in patients with various diseases involving defense mechanisms. According to these findings, it could be inferred that ADA activity in serum would follow the same behavior as observed in a rat thymus. So, we have analyzed if its determination could be considered a functional biochemical parameter in populations at nutritional risk. We analyzed the serum ADA activity in groups of individuals with altered nutritional status evaluated through different markers--young adult patients with Nervous Anorexia, overweight or obese school children, children suffering cystic fibrosis. The results show a statistically significant increase in the ADA activity in all groups, with respect to their healthy controls--same age range and socio economic status. The results obtained to date suggest the importance of including the determination of serum Adenosine Deaminase activity in the biochemical evaluation of the nutritional status, as a functional marker related to defense mechanisms.

Serum Adenosine Deaminase in patients with Type-2 Diabetes Mellitus and its Relation with Blood Glucose and Glycated Haemoglobin levels

Background: Diabetes mellitus is a metabolic characterized bydeficiency of insulin and insulin resistance. Adenosine deaminase (ADA) modulates the bioactivity of insulin and Adenosine receptorsstimulate glucogenolysis and gluconeogenesis . but its role in Type 2 diabetes mellitus is not yet characterized. Aim & Objectives : The present study aimed to evaluate the serum Adenosine Deaminase level and to correlate ADA levels with Blood Glucose and Glycated hemoglobin levels in Type-2 Diabetes Mellitus patients. Material and Method: The study population of 120 patients were divided into 3 groups: Group A which consisted of 40 normal healthy individuals without any complication or history of Diabetes. Group B included 40 patients of Type 2 Diabetes Mellitus both with HbA1c 7% (n=40). Fasting blood sugar, HbA1c, ADA, and body mass Index were estimated in all the subjects under study. Results: The study showed that mean Fasting Blood Sugar, Post prandial Blood sugar and HbA1c concentration was significantly higher in Group C & Group B compared to Group A. Compared with the well-controlled Type-2 Diabetes Mellitus patients (HbA1c 7%) showed significantly increased ADA activity (49.79 18.12 U/L vs. 90.10 32.75; P <0.001). The correlation between Adenosine Deaminase and HbA1c was positive and significant in both Group B (r= 0. 389; p= 0.007) and Group C (r = 0.430; p<0.001). Conclusion: Serum ADA levels may have an important role in determining the glycemic status in Diabetics. A positive correlation between ADA level with glycemic control suggest its important role in glucose and lipid metabolic derangements seen in Type 2 Diabetes Mellitus patients.

Role of adenosine deaminase in alteration of cortisol and tumor necrosis factor α concentration following exhaustive exercise sessions

Context: Cortisol and tumor necrosis factor-α (TNF-α) has a significant role on the immune system. Previous studies have shown a significant increase in cortisol and TNF-α in athlete; however, the alteration of adenosine deaminase (ADA) activity in athletes has not been previously reported. Aims: This study was aimed to investigate the effect of exhaustive exercise on cortisol, TNF-α and serum ADA activity in endurance runners. Settings and Design: All endurance male athletes were enrolled in this case control study. Subjects and Methods: The participants were submitted to the same experimental protocol used in the exercise trials, they run on a treadmill until exhausting state. Saliva and blood sample were collected in resting and immediately after exercise; serums were separated and stored at −70°C pending assays. Serum was analyzed for ADA activity and TNF-α. Salivary cortisol measured by enzyme-linked immunosorbent assay method. Statistical Analysis Used: Data was analyzed using the statistical package for the social sciences 16 (SPSS Inc., Chicago) and one-sample Kolmogorov-Smirnov test. Results were presented as mean ± standard deviation and independent samples t-test used to compare mean differences. In addition, linear regression analysis was performed and means of the Pearson's correlation coefficient (r) were determined to show the correlation between variables. Results: Cortisol and TNF-α elevated following intensified training compared with the resting state. There was a significant increase in serum ADA activity between athletes and non-athletes groups. In addition, our results showed a strong direct correlation between serum total ADA activity and TNF-α. Conclusions: Based on the obtained data, an acute period of intensified training can induce an increase of ADA activity accompanies with the increase of cortisol and TNF-α. ADA is involved in the immune system development. Our results hypothesized that ADA can be associated with an increase in fatigue which lends to reduced physical activity. We showed that excessive exercise can induce an inflammatory response resulting in elevated levels of cortisol and TNF-α and perhaps by increasing activity of adenosin deaminase.