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The aim of this study was to investigate the toxicity of Syzygium jambos and Solanum guaraniticum leaf extracts, through Artemia salina lethality testing and cytotoxicity evaluations in rat spleen lymphocytes, using methyl tetrazolium (MTT), neutral red uptake (NRU), trypan blue dye exclusion, and lactate dehydrogenase (LDH) leakage assays, besides by their in vitro effects on acetylcholinesterase (AChE) activity. The LC50 calculated in the A. salina bioassay demonstrated that both extracts might well be toxic. Solanum guaraniticum presented cytotoxic effects against lymphocytes, as demonstrated by viable cells count reductions, NR uptake, and increased LDH leakage. Syzygium jambos appears to present immunomodulatory properties, increasing lymphocyte mitochondrial activity and inhibiting AChE activity. The results demonstrated the possible harmful effects of these vegetal preparations and may be helpful in therapeutic decisions and future studies with respect to the toxicology of these extracts, when used as phytotherapeutic medicines.

Background This study investigated the association between urinary levels of interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) with estimated glomerular filtration rate (eGFR), urinary albumin/creatinine ratio (uACR), and urinary neutrophil gelatinase-associated lipocalin (uNGAL) in patients with type 2 diabetes (T2D). Methods Urinary concentrations of IL-6, IL-10, TNF-α, ACR, and NGAL were measured in 121 patients with T2D. Results Urinary IL-6 and TNF-α increased 45.5% and 49.4% in the highest uACR quartile compared to lowest quartile. Urinary IL-10 levels decreased 40.9% in the highest uACR quartile compared to the lowest quartile. Urinary IL-6 and TNF-α were 75.3% and 81.6%, higher in the highest uNGAL quartile compared to the lowest quartile. Urinary IL-10 concentration was 69.8% lower in patients from the highest uNGAL quartile compared to lowest quartile. Conclusions Urinary IL-6, IL-10, and TNF-α were associated with indicators of glomerular and tubular injuries in patients with T2D.

Glioma is a malignant brain tumor with rapid proliferation, infiltrative growth, poor prognosis and it is chemoresistent. Pomegranate seed oil (PSO) has antioxidant, anti-inflammatory and antitumor properties. This study showed the optimization of PSO nanoemulsions (NEs) as an alternative for glioma treatment.The study aimed to evaluate PSO NEs cytotoxicity on human blood cells and antiglioma effects against C6 cells.NEs were prepared by the spontaneous emulsification method, using PSO at 1.5 and 3.0%, and were evaluated regarding their physical stability and antioxidant activity. Toxicity evaluations in human blood cells were performed in terms of cell viability, genotoxicity, lipid peroxidation, protein carbonylation, catalase activity and hemolysis at 0.1, 0.25 and 0.5 mg/mL PSO, after a 72-h incubation period. In vitro antitumor effect was determined against glioma cells after 24 and 48 h, and astrocytes were used as a non-transformed cell model.Formulations presented droplet size below 250 nm, low polydispersity index, negative zeta potential and pH in the acid range. NEs and PSO had scavenging capacity around 30% and promoted a proliferative effect in mononuclear cells, increasing about 50% cell viability. No genotoxic and oxidative damage was observed in lipid peroxidation, protein carbonylation and catalase activity evaluations for NEs. Hemolysis study showed a hemolytic effect at high concentrations. Moreover, formulations reduced only tumor cell viability to 47%, approximately.Formulations are adequate and safe for intravenous administration. Besides, in vitro antitumor activity indicates that NEs are promising for glioma treatment.

Syzygium cumini seeds were used for the preparation of an aqueous extract (ASc) and of polymeric nanoparticles containing ASc (NPASc) with the aim to evaluate and compare their in vitro efficacy against the complications of Diabetes mellitus (DM) and the in vivo toxicity. NPASc were produced by the emulsification/evaporation solvent technique, employing poly-e-caprolactone, a biocompatible polymer. The antioxidant activity of both ASc and NPASc was evaluated by the scavenging of DPPH radicals and by the ferric reducing antioxidant power assay (FRAP). The in vitro efficacy of both formulations against oxidized LDL particles (ox-LDL) and fungal species was also assessed. NPASc presented properties compatible with nanometric systems, and chromatogram analysis demonstrated that the composition of S. cumini was not affected. The antioxidant properties of the extract were also maintained in the new formulation. Indeed, both formulations showed high protection against ox-LDL. The antifungal activity of NPASc against Candida guilliermondii and Candida haemulonii was superior to that observed for the ASc. No acute toxicity was observed in the Artemia salina lethality assay and in rats. These findings highlight the possibility of expanding the use of S. cumini to ameliorate the chronic complications of DM. The lack of toxicity of the nanoparticles indicates that NPASc might be a safe candidate for drug delivery systems.

Solanum guaraniticum is a medicinal plant traditionally used to treat gastric and liver diseases. However, there is no documented evidence corroborating its safety. The present study evaluated the potential toxicity of S. guaraniticum leaf extract after acute administration in rats. Single doses of the extract (1.250, 2.500, and 5.000 mg/kg) were administered by gavage, and the rats were then monitored for 48 h and/or 14 days. Mortality, acute signs of toxicity, and general activity in the open field test were assessed as well as hematological and biochemical parameters, enzymatic activity (δ-aminolevulinate dehydratase and acetylcholinesterase), and oxidative stress parameters (lipid peroxidation level, non-protein thiol content, tissue catalase activity, and serum ferrous reducing power). Phytochemical analysis was also performed by HPLC. The results showed that extract administration produced no deaths (LD50 > 5,000 mg/kg), and no significant adverse effects regarding food consumption, body weight gain, gross pathology, or other parameters. However, the open field tests showed a decrease in spontaneous activity (crossing and rearing) mainly at 48 h after treatment. The results suggest that S. guaraniticum extract is not acutely toxic, but causes alterations in central nervous system activity. RESUMO Solanum guaraniticum é uma planta medicinal tradicionalmente usada para tratar doenças gástricas e hepáticas. Porém, não há evidências documentadas sobre sua segurança. O presente estudo avaliou a toxicidade do extrato das folhas de S. guaraniticum após administração aguda em ratos. Doses únicas do extrato (1.250, 2.500 and 5.000 mg/kg) foram administradas por gavagem e os animais foram monitorados por 48 h ou 14 dias. Mortalidade, sinais de toxicidade aguda e atividade geral, através do teste de campo aberto, foram analisados, assim como parâmetros hematológicos e bioquímicos, atividades enzimáticas (δ-aminolevulinato desidratase e acetilcolinesterase) e parâmetros de estresse oxidativo (nível de peroxidação lipídica, conteúdo de tióis não protéicos, atividade da catalase em tecidos e poder redutor em soro). A análise fitoquímica também foi realizada por HPLC. Os resultados mostraram que a administração do extrato não provoca mortes (LD50>5.000 mg/kg) ou efeitos adversos significativos com relação ao consumo de comida, ganho de peso corporal, análise patológica, entre outros. Entretanto, o teste de campo aberto mostrou uma diminuição na atividade espontânea geral (cruzamentos e levantadas), principalmente em 48 h após o tratamento. Portanto, nossos resultados sugerem que o extrato de S. guaraniticum não é agudamente tóxico, mas causa alterações na atividade do sistema nervoso central.

The accumulation of advanced oxidation protein products (AOPPs) has been linked to several pathological conditions. Here, we investigated collagen as a potential source for AOPP formation and determined the effects of hypochlorous acid (HOCl)-treated collagen (collagen-AOPPs) on human neutrophil activity. We also assessed whether alpha-tocopherol could counteract these effects. Exposure to HOCl increased the levels of collagen-AOPPs. Collagen-AOPPs also stimulated the production of AOPPs, nitric oxide (NO), superoxide radicals (O2 −), and HOCl by neutrophils. Collagen-AOPPs induced apoptosis and decreased the number of viable cells. Alpha-tocopherol prevented the formation of collagen-AOPPs, strongly inhibited the collagen-AOPP-induced production of O2 − and HOCl, and increased the viability of neutrophils. Our results suggest that collagen is an important protein that interacts with HOCl to form AOPPs, and consequently, collagen-AOPP formation is related to human neutrophil activation and cell death.

Renal dysfunction has been reported in normoalbuminuric patients, demonstrating the necessity to improve the diagnostic and prognostic tools for diabetic kidney disease (DKD) investigation. Therefore, the aim of this study was to investigate whether the urinary levels of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are increased in type 2 diabetes mellitus (DM) patients with normal or mildly increased albuminuria.In this study, 117 type 2 DM patients classified into three groups according to urinary albumin/creatinine ratio (uACR): uACR10mg/g creatinine, uACR 10-30mg/g creatinine and uACR30mg/g creatinine were enrolled. Urinary concentrations of KIM-1 (uKIM-1) and NGAL (uNGAL) were measured.uKIM-1 levels increased progressively from uACR10mg/g creatinine (69.0±20.8pg/ml) to uACR 10-30mg/g creatinine (106.1±41.2pg/ml) and to uACR30mg/g creatinine (166.0±31.9pg/ml) (P0.001). In addition, uNGAL levels increased progressively from uACR10mg/g creatinine (29.5±8.8ng/ml) to uACR 10-30mg/g creatinine (51.7±10.9ng/ml) and to uACR30mg/g creatinine (71.0±9.6ng/ml) (P0.001) patients. Similarly, both uKIM-1 and uNGAL adjusted by urinary creatinine were increased in patients with uACR 10-30mg/g creatinine. Significant and positive correlations were observed between uACR, uKIM-1 and uNGAL.uKIM-1 and uNGAL were increased in type 2 DM patients with normal or mildly increased albuminuria, which indicates that tubular and glomerular injuries may be occurring even at the earliest stage of DKD.

Uric acid presents different roles in an organism, since it can act as an antioxidant or a pro-oxidant molecule. High serum uric acid levels may cause damage to several structures, including nucleic acids and its components. Therefore, in this study the association between increased serum uric acid concentrations and oxidation of nucleosides was investigated by assessment of urinary 8-hydroxydeoxyguanosine (8-OHdG) in patients with type 2 diabetes (T2D) and in healthy individuals. Urinary 8-OHdG and biochemical parameters were assessed in 61 patients who were initially grouped into 2 groups based on the median serum uric acid levels (5.3 mg/dL and ≥5.3 mg/dL). Urinary 8-OHdG was higher in patients with T2D and serum uric acid levels ≥5.3 mg/dL, when compared with the patients with serum uric acid levels5.3 mg/dL; however, co-occurrence of high serum uric acid with high urinary 8-OHdG was not observed in healthy individuals. A significant positive correlation between 8-OHdG and uric acid (r = 0.40, P 0.01) was observed in patients with T2D. High serum uric acid levels were associated with high urinary 8-OHdG levels in patients with T2D, and this association was independent of gender, hypertension, body mass index, and serum creatinine.

The aim of the study was to investigate the association between Glutathione S-transferase P1 (GSTP1) gene polymorphism with obesity and markers of cardiometabolic risk. A cross-sectional study was carried out in individuals aged≥18 and ≤30 years. The study included 54 normal weight, 27 overweight and 68 obese volunteers. Anthropometric measurements and biochemical parameters were evaluated, the DNA was extracted from blood samples and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to measure GSTP1 Ile105Val gene polymorphism of the study participants. Also, biochemical analysis and hormone assays were carried out. A positive association between GSTP1 polymorphism and obesity was observed on subjects carrying at least one G allele (AG and GG). GG genotype was found only in the obese group. The G allele carriers presented 2.4 times higher chance of obesity when compared to those with the AA genotype. These results were independent of sex and age. We suggest that despite a study in population regional (south of Brazil), the GSTP1 gene polymorphism may play a significant role in the increase of susceptibility of obesity and contribute to identify the cardiovascular risk in young adults.

Objective This study aimed to investigate the effect of the leaf extracts of Syzygium jambos and Solanum guaraniticum on the δ-aminolevulinate dehydratase (δ-ALA-D) activity, their antioxidant activity and potential protective action on oxidatively stressed erythrocytes, in order to demonstrate the safety or toxicity of the plant. Methods In erythrocyte samples, the effect of both extracts on δ-ALA-D activity, H(2)O(2)-induced oxidative stress, and 2,2′azobis (2-amidinopropane) (AAPH)-induced hemolysis was evaluated, as well as some antioxidant mechanisms. Results Both extracts inhibited δ-ALA-D activity (S. guaraniticum > S. jambos), and an involvement of the zinc ion of the δ-ALA-D structure on the inhibition of enzyme activity was verified. S. jambos leaf extract showed marked efficiency in countering H(2)O(2)-induced lipid peroxidation and in maintaining cellular integrity against AAPH-induced hemolysis. Furthermore, S. jambos exhibited greater H(2)O(2) scavenging activity and stronger reduction power than S. guaraniticum. Discussion Both extracts bear potent antioxidant property as an important beneficial effect. However, the inhibition of δ-ALA-D activity suggests a possible harmful effect of these vegetal preparations and indicates the need for further investigation regarding their toxicological properties. All together, these data represent a significant contribution to the knowledge of these plants, both to the scientific community and to the folk medicine.

Ethnopharmacological relevance The infusion or decoction of Mirabilis jalapa leaves is used in traditional medicine in Brazil to treat inflammatory and painful diseases. Thus, the present study was designed to investigate whether the leaf ethyl acetate (Eta) fraction from Mirabilis jalapa exhibits antinociceptive effect in clinically relevant pain models in mice. Furthermore, we have investigated the role of cholinergic system in the antinociceptive action produced by Eta in mice. Materials and methods The effect of Eta administered orally (10 mg/kg, p.o.) in mice was verified on the painful hypersensitivity (mechanical allodynia) in models of chronic inflammation (subcutaneous injection of complete Freund’s Adjuvant—CFA in the plantar surface of the right hind paw), postoperative (paw surgical incision) and neuropathic (partial sciatic nerve ligation) pain. In the chronic inflammation model, we further verified the effect of Eta treatment on paw edema and interleukin-1β (IL-1β) levels. We also investigated the role of muscarinic and nicotinic receptors in the antiallodynic action produced by Eta as well as the possible action of Eta on in vitro and ex vivo acetylcholinesterase activity in CFA treated animals. Furthermore, we verified the effect of Eta treatment on the parameters of liver and kidney lesion (level of urea, and activity of aspartate aminotransferase and alanine aminotransferase). Results Eta produced marked reduction in the allodynia caused by CFA, surgical incision and partial sciatic nerve ligation. However, Eta did not alter the paw edema or the increase of IL-1β levels produced by CFA. The antinociceptive effect of Eta was reversed by the pre-treatment of animals with the antagonists of muscarinic (atropine, 5 mg/kg, s.c) or nicotinic (mecamylamine, 0.001 mg/kg, s.c.) receptors. Eta did not alter in vitro acetylcholinesterase activity in blood or spinal cord samples, but it reversed the increase in the acetylcholinesterase activity observed in the spinal cord samples from mice injected with CFA. Moreover, Eta did not alter the indicators of liver or kidney lesion. Conclusions Based on its use in traditional medicine, the results of the present study confirmed the antinociceptive properties of Eta in clinically relevant pain models. Also its effect on the CFA-induced chronic inflammation seems to be related to acetylcholinesterase inhibition and cholinergic system.

It is well known that the levels of adenosine in the brain increase dramatically during cerebral hypoxic-ischemic (HI) insults. Its levels are tightly regulated by physiological and pathophysiological changes that occur during the injury acute phase. The aim of the present study was to examine the effects of the neonatal HI event on cytosolic and ecto-enzymes of purinergic system--NTPDase, 5'-nucleotidase (5'-NT) and adenosine deaminase (ADA)--in cerebral cortex of rats immediately post insult. Furthermore, the Na(+)/K(+)-ATPase activity, adenosine kinase (ADK) expression and thiobarbituric acid reactive species (TBARS) levels were assessed. Immediately after the HI event the cytosolic NTPDase and 5'-NT activities were increased in the cerebral cortex. In synaptosomes there was an increase in the ecto-ADA activity while the Na(+)/K(+) ATPase activity presented a decrease. The difference between ATP, ADP, AMP and adenosine degradation in synaptosomal and cytosolic fractions could indicate that NTPDase, 5'-NT and ADA were differently affected after insult. Interestingly, no alterations in the ADK expression were observed. Furthermore, the Na(+)/K(+)-ATPase activity was correlated negatively with the cytosolic NTPDase activity and TBARS content. The increased hydrolysis of nucleotides ATP, ADP and AMP in the cytosol could contribute to increased adenosine levels, which could be related to a possible innate neuroprotective mechanism aiming at potentiating the ambient levels of adenosine. Together, these results may help the understanding of the mechanism by which adenosine is produced following neonatal HI injury, therefore highlighting putative therapeutical targets to minimize ischemic injury and enhance recovery.

The aim of this study was to investigate whether urinary levels of interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) are altered in normoalbuminuric patients with type 2 diabetes mellitus (T2DM), and whether these cytokines are able to identify diabetic kidney disease (DKD) among these patients.This study included 125 T2DM patients classified into 3 groups according to urinary albumin/creatinine ratio (uACR): uACR10mg/g creatinine, uACR 10-30mg/g creatinine and uACR30mg/g creatinine. Urinary inflammatory cytokines were measured.The urinary IL-6 concentrations increased from uACR10 (97.2±26.4pg/ml) to uACR 10-30 (113.6±28.0pg/ml) and to uACR30mg/g creatinine (163.5±25.6pg/ml) (P0.05 and P0.001, respectively) patients. The urinary IL-10 concentrations decreased in these uACR ranges [100.0 (58.0-141.0) pg/ml vs. 62.0 (54.5-71.5) pg/ml vs. 42.0 (32.0-48.0) pg/ml] (P0.05 and P0.001, respectively). All urinary cytokines demonstrated good ability to identify DKD (areas under curves0.9).Urinary inflammatory cytokines, especially IL-6 and IL-10, may assist in the identification of DKD in T2DM patients, even in the absence of micro- and macroalbuminuria.

Methylmercury (MeHg) is an organic form of mercury with toxic effects in multiple organs. The aim of the present investigation was to evaluate the in vivo effects of MeHg (1 and 4 mg/kg) given orally for seven consecutive days on adenosine deaminase (ADA), n-acetyl-β-D-glucosaminidase (NAG) and ecto-nucleoside triphosphate phosphohydrolase (NTPDase) activities, and on lipid peroxidation in hippocampus, cerebral cortex, kidney and liver of suckling rat pups. The results showed that NAG activity and lipid peroxidation levels increased in the kidney in both treatments, whereas urinary NAG activity increased only in the 1 mg/kg treatment. Despite the fact that the lipid peroxidation increased in both cerebral cortex and hippocampus, the latter appeared to be more vulnerable to MeHg exposure as it also had an increase in ADA activity. Thus, although dietary MeHg modified renal cell function, it did not alter histological features in suckling rat pups. The results of our investigation are of significant importance because they demonstrated responses to exposition to low doses of MeHg in target organs during the development of the rat. Especially the kidney was affected by the oral exposure to MeHg, suggesting the vulnerability of this organ at this stage of development. Moreover, the urinary NAG may provide important data that could serve as basis for risk assessment purposes following MeHg exposure.

Syzygium cumini (Sc) have been intensively studied in the last years due its beneficial effects including anti-diabetic and anti-inflammatory potential. Thus, the aim of this study was to evaluate the effect of aqueous seed extract of Sc (ASc) in the activity of enzymes involved in lymphocyte functions. To perform this study, we isolated lymphocytes from healthy donors. Lymphocytes were exposed to 10, 30, and 100 mg/mL of ASc during 4 and 6 h and adenosine deaminase (ADA), dipeptidyl peptidase IV (DPP-IV), and acetylcholinesterase (AChE) activities as well as CD26 expression and cellular viability were evaluated. ASc inhibited the ADA and DPP-IV activities without alteration in the CD26 expression (DPP-IV protein). No alterations were observed in the AChE activity or in the cell viability. These results indicate that the inhibition of the DPP-IV and ADA activities was dependent on the time of exposition to ASc. We suggest that ASc exhibits immunomodulatory properties probably via the pathway of DPP-IV-ADA complex, contributing to the understanding of these proceedings in the purinergic signaling.

Chagas disease (CD) is a chronic and endemic illness caused by the parasite Trypanosoma cruzi. Microvascular disturbances play an important role in the progress of the disease. The purinergic signaling system participates in regulatory functions, such as immunomodulation, neuroprotection, and thromboregulation. This study aimed to investigate the activities of purinergic system ecto-enzymes present on the platelet surface and the platelet aggregation profile from patients with indeterminate form of Chagas disease (IFCD). Thirty patients diagnosed with IFCD and 30 healthy subjects were selected. Ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase), ecto-nucleotide pyrophosphatase/phosphodiesterase (E-NPP), ecto-5′-nucleotidase (E-5′-NT) and ecto-adenosine deaminase (E-ADA) activities were measured in platelets isolated from these individuals as well as the platelet aggregation. Results demonstrated an increase of 21 % in the E-NPP activity and 30 % in the E-5′-NT activity in IFCD group (P

To investigate the activity of δ-Aminolevulinate dehydratase (δ-ALA-D) and its possible relationship with oxidative status, lipid profile, body mass index (BMI) in type 2 diabetics (DM2) patients.δ-ALA-D activity and reactivation index, as well as markers of oxidative stress and biochemical and anthropometrics parameters were determined in DM2 patients (n = 63) and controls (n = 63).There was a decreased δ-ALA-D activity and a higher reactivation index (p0.05) in DM2 patients besides an elevated level of oxidative stress. Disturbances on lipid profile were related to the enzymatic activity and BMI also was correlated with oxidative level in DM2 patients (p0.05).There is an association between oxidative stress, abnormalities on lipid profile, distribution of body fat and δ-ALA-D activity inhibition as well as the enzyme is more oxidized in the DM2 suggesting that it would be a good biomarker for assessing prejudice in chronic metabolic processes.

The aim of the present study was to investigate the effect of curcumin (Cur) on the activity of ectonucleoside triphosphate diphosphohydrolase (CD39), 5'-nucleotidase (CD73) and adenosine deaminase in platelets of cigarette smoke-exposed rats. For that purpose, we subjected male Wistar rats to a treatment with Cur and cigarette smoke, once a day, 5 days each week, for 30 days. The rats were treated by gavage with Cur or corn oil and then exposed to cigarette smoke. The experimental procedures were divided into two sets of experiments. In the first, the animals were divided into four groups: vehicle (corn oil) or Cur 12·5, 25 or 50 mg·kg-1. In the second, the animals were divided into five groups: vehicle (corn oil), smoke, or smoke and Cur 12·5, 25 or 50 mg·kg-1. The results showed that treatment with Cur significantly prevented the increased adenosine triphosphate (ATP) (121%) and adenosine monophosphate (AMP) (159%) and the decreased adenosine diphosphate (ADP) (51%) hydrolysis observed in the cigarette smoke-exposed rats Our results suggest that those purinergic enzyme alterations observed in the cigarette smoke-exposed rats could be related to an excessive platelet aggregation and point toward the potential of Cur to modulate purinergic signalling and, consequently, regulate the thrombus formation. Copyright © 2011 John Wiley & Sons, Ltd.

Nucleotide and nucleoside-degrading enzymes, such as nucleoside triphosphate diphosphohydrose (NTPDase), 5'-nucleotidase and adenosine deaminase (ADA) are present in the surface membranes of platelets, involved in clotting disturbances of Trypanosoma evansi-infected animals. Thus, this study was aimed at evaluating the activities of these enzymes in platelets of rats experimentally infected with T. evansi. Animals were divided into four groups, according to the level of parasitemia. Blood samples were collected on days 3 (group A: at the beginning of parasitemia), 5 (group B: high parasitemia) and 15 (group C: chronic infection), post-infection. Group D (control group) was composed of non-infected animals for platelet count, separation and enzymatic assays. Animals from groups A and B showed marked thrombocytopenia, but platelet count was not affected in chronically infected rats. NTPDase, 5'-nucleotidase and ADA activities decreased (p0.05) in platelets from rats of groups A and B, when compared to the control group. In group C, only NTPDase and 5'-nucleoside activities decreased (p0.001). The correlations between platelet count and nucleotide/nucleoside hydrolysis were positive and statistically significant (p0.05) in groups A and B. Platelet aggregation was decreased in all infected groups, in comparison to the control group (p0.05). It is concluded that the alterations observed in the activities of NTPDase, 5'-nucleotidase and ADA in platelets of T. evansi-infected animals might be related to thrombocytopenia, that by reducing the number of platelets, there was less release of ATP and ADP. Another possibility being suggested is that changes have occurred in the membrane of these cells, decreasing the expression of these enzymes in the cell membrane.

Selenium (Se) is a dietary essential trace element with important biological roles. Sodium selenate (Na(2)SeO(4)) is an inorganic Se compound used in human and animal nutrition that acts as precursor for selenoprotein synthesis. The organoselenium 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one (C(21)H(2)HOSe) is an α,β-unsaturated ketone functionalized vinyl chalcogenide that has been found as a potential tool in organic synthesis. Adenosine deaminase (ADA) is an important enzyme in the degradation of adenine nucleotides. In this study, we investigated the in vitro effects of both Se compounds on ADA activity and cell viability in leukocyte suspension (LS) of healthy donors (n=12). We first observed an inhibition of ADA activity using 0.1 μM of 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one, and an increase in cellular viability when 30 μM were used. However, we did not observe alterations in the presence of sodium selenate. Moreover, both Se compounds did not alter lactate dehydrogenase activity and thiobarbituric acid reactive substance levels. These results suggest that the inhibition of ADA activity caused by α,β-unsaturated ketone may affect the adenosine levels in LS and modulate cell viability, attenuating conditions that involve the activation of the immune system.

The study was undertaken to evaluate changes in the activity of adenosine deaminase (ADA) in brains of rats infected by Trypanosoma evansi. Each rat was intraperitoneally infected with 10(6) trypomastigotes either suspended in fresh (group A; n = 13) and cryopreserved blood (group B; n = 13). Thirteen animals were used as control (group C). ADA activity was estimated in the cerebellum, cerebral cortex, striatum and hippocampus. No differences (P0.05) in ADA activity were observed in the cerebellum between infected and non-infected animals. Significant (P0.05) reductions in ADA activity occurred in cerebral cortex in acutely (day 4 post-infection; PI) and chronically (day 20 PI) infected rats. ADA activity was significantly (P0.05) decreased in the hippocampus in acutely infected rats, but significantly (P0.05) increased in the chronically infected rats. Significant (P0.05) reductions in ADA activity occurred in the striatum of chronically infected rats. Parasites could be found in peripheral blood and brain tissue through microscopic examination and PCR assay, respectively, in acutely and chronically infected rats. The reduction of ADA activity in the brain was associated with high levels of parasitemia and anemia in acute infections. Alterations in ADA activity of the brain in T. evansi-infected rats may have implications for pathogenesis of the disease.

Diabetes mellitus, a chronic metabolic disorder, has assumed epidemic proportions and its long-term complications can have devastating consequences. The oxidative stress in diabetes was greatly increased due to prolonged exposure to hyperglycemia and impairment of oxidant/antioxidant equilibrium. Syzygium cumini is being widely used to treat diabetes by the traditional practitioners over many centuries. Adenosine deaminase (ADA) and 5′-Nucleotidase (5′NT) are enzymes of purine nucleoside metabolism that play an important role in the regulation of adenosine (Ado) levels. In this study, we investigated the effect of Syzygium cumini aqueous leaves extract (ASc) on ADA and 5′NT activities and on parameters of oxidative stress under in vitro conditions, using platelets of patients with Type 2 diabetes mellitus. Platelet-Rich Plasma (PRP) was assayed by ADA, 5′NT, Catalase (CAT), Superoxide Dismutase (SOD) activities and Thiobarbituric acid reactive substances (TBARS) levels. We observed that ADA, 5′NT activities and TBARS levels were significantly higher when compared to the control group, and ASc (100 and 200 µg/mL) prevented these effects. Our study demonstrates that ASc was able to remove oxidant species generated in diabetic conditions and modulates in the Ado levels. Then, ASc may promote a compensatory response in platelet function, improving the susceptibility-induced by the diabetes mellitus.

Background Ischemia-modified albumin (IMA) has been shown to be a rapidly rising and sensitive biochemical marker for the diagnosis of myocardial ischemia. In this study, we evaluated the levels of IMA in myocardial infarction and prostate diseases, as well as the influence of HDL cholesterol levels on C-reactive protein (CRP) and IMA levels. Methods A total of 27 patients with myocardial infarction (MI), 102 patients with benign prostatic hyperplasia (BPH), 84 patients with prostate cancer (PCA), and 21 healthy subjects were enrolled in this study. IMA levels were measured in whole studied patients. Cardiac troponin I (cTnI), cholesterol, HDL cholesterol, and CRP were measured in MI and control groups. Results IMA values were significantly higher in patients with MI (0.5215 ± 0.0241 ABSU) and BPH (0.4150 ± 0.0156 ABSU) in comparison to control subjects (0.3381 ± 0.0194 ABSU). IMA and CRP were higher in MI group, especially in patients with HDL cholesterol levels lower than 38 mg/dL. The ability of IMA to discriminate myocardial infarction was higher than CRP. Significant correlations between CRP and HDL, CRP and IMA, and HDL and IMA were reported. Conclusions IMA and CRP increase in myocardial damage, and the decrease of HDL cholesterol appears to enhance the inflammatory response. IMA also increase in benign prostate hyperplasia and this finding suggests that the diagnosis of prostate diseases must be considered on evaluation of IMA as a marker of cardiac ischemia.

Syzigium cumini (L.) Skeels from the Myrtaceae family is among the most common medicinal plants used to treat diabetes in Brazil. Leaves, fruits, and barks of S. cumini have been used for their hypoglycemic activity. Adenosine deaminase (ADA) is an important enzyme that plays a relevant role in purine and DNA metabolism, immune responses, and peptidase activity. ADA is suggested to be an important enzyme for modulating the bioactivity of insulin, but its clinical significance in diabetes mellitus (DM) has not yet been proven. In this study, we examined the effect of aqueous leaf extracts of S. cumini (L.) (ASC) on ADA activity of hyperglycemic subjects and the activity of total ADA, and its isoenzymes in serum and erythrocytes. The present study indicates that: (i) the ADA activity in hyperglycemic serum was higher than normoglycemic serum and ADA activity was higher when the blood glucose level was more elevated; (ii) ASC (60-1000 microg/mL) in vitro caused a concentration-dependent inhibition of total ADA activity and a decrease in the blood glucose level in serum; (iii) ADA1 and 2 were reduced both in erythrocytes and in hyperglycemic serum. These results suggest that the decrease of ADA activity provoked by ASC may contribute to control adenosine levels and the antioxidant defense system of red cells and could be related to the complex ADA/DPP-IV-CD26 and the properties of dipeptidyl peptidase IV (DPP-IV) inhibitors which serve as important regulators of blood glucose.

Aims Diabetes mellitus is associated with platelet alterations that may contribute to the development of cardiovascular complications. The present study investigates the effects of resveratrol (RSV), an important compound with cardioprotective activities, on NTPDase, ecto-nucleotide pyrophosphatase/phosphodiesterase (E-NPP), 5′-nucleotidase and adenosine deaminase (ADA) activities in platelets from streptozotocin (STZ)-induced diabetic rats. Main methods The animals were divided into six groups (n = 8): control/saline; control/RSV 10 mg/kg; control/RSV 20 mg/kg; diabetic/saline; diabetic/RSV 10 mg/kg; diabetic/RSV 20 mg/kg. RSV was administered during 30 days and after this period the blood was collected for enzymatic assay. Key findings The results demonstrated that NTPDase, E-NPP and 5′-nucleotidase activities were significantly higher in the diabetic/saline group (P

In nervous tissue, the calcium (Ca 2+ ) release induces neurotransmitter exocytosis and synaptic plasticity in neurons and is essential for Ca 2+ waves and oscillations in astrocytes. In this work, we have investigated the effect of organocalchogens on calcium influx in synaptosomal preparations under basal and depolarizing conditions. Acute administration of ebselen caused a significant increase of 34% (p < 0.05) Ca 2+ influx, when under basal conditions but showed no effect on potassium stimulated calcium conditions by brain synaptosomes. Diphenyl ditelluride (PhTe) 2 increased 45 Ca 2+ influx by 40% (p < 0.05) under depolarizing conditions, while diphenyl diselenide (PhSe) 2 had no effect on the brain synaptosomes studied. In addition, we characterized an "in vitro" model with the purpose of studying Ca 2+ movements in slices. In this model, we examined the effect of diorganylchalcogenides using brain hippocampal slices, which showed the decrease of calcium influx with the three drugs studied. These findings showed that there are different effects of diorganylchalcogenides in the different models evaluated. It is possible that these differential effects result from the action of neural signal transduction pathways at different levels, possibly involving neurotransmitter release and channel targeting.

Background Diabetes mellitus (DM) is a heterogeneous group of metabolic disorders which affects over 10% of the world population. The diabetes-induced oxidized low-density lipoprotein (ox-LDL) can affect several components of the atherogenic process [1]. Nanodosage forms can provide advantages for herbal drugs, including increase of therapeutic index, improvement of stability and controlled delivery.

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.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).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.(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.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.

Objective The aim of the study was to assess the influence of overweight and obesity in youth on adipocytokines levels, inflammatory and oxidative markers. Design and methods Cross-sectional study of 149 young adults (54 normal weight, 27 overweight, 68 obese).Clinical and biochemical parameters, including lipid profile, fasting glucose, insulin and HOMA were determined. The levels of adipocytokines(adiponectin, retinol-binding protein 4 (RBP4), and resistin), markers of inflammation (high-sensitivity C-reactive protein (hs-CRP) adenosine deaminase (ADA), dipeptidyl peptidase-IV (DPP-IV) activities, serum IL-6 levels and oxidative stress (malondialdehyde and ferric reducing antioxidant power — FRAP) were measured. Results Obese subjects presented significantly lower levels of Sulfhydryl groups (SH groups), adiponectin, HDL-C and the highest levels of RBP4, hs-CRP, resistin, IL-6, ADA, DPP-IV activities, and oxidative markers than compared to those who were of normal weight. There was a positive correlation between hs-CRP, IL-6, DDP-IV activity, anthropometric measurements and biochemical parameters. Conclusions This analysis shows that resistin, RBP4, IL-6, ADA and DPP-IV activities and the reduction of adiponectin can promote inflammation, impairment of insulin sensitivity, and may contribute development of the pathways involved in obesity. These findings may hold promise in identifying new inflammatory markers, benchmarks that assist in the diagnosis and monitoring of patients with overweight and obese.

An in vitro evaluation on the antioxidant effect of diphenyl diselenide (PhSe)(2), an organochalcogenide, against sodium nitroprusside (SNP)-induced lipid peroxidation (LPO) was conduced. Human platelets and erythrocyte membranes (ghosts), as well as rat brain homogenates (S(1)), were pre-incubated with different concentrations of SNP (0-10 microM). All SNP concentrations tested significantly increased LPO in human platelets and S(1). Platelets were more sensitive to SNP-induced peroxidative damage when compared to S(1). SNP 10 microM decreased glutathione peroxidase (GPx) activity and did not affect glutathione reductase (GR) and catalase (CAT) activities in human platelets. However, ghosts were insensitive to SNP-induced LPO and no changes on GPx, GR and CAT activities were observed. Diphenyl diselenide significantly protected human platelets against SNP-induced LPO and recovered GPx inactivation. This effect was more evident at (PhSe)(2) concentrations above 2 microM. The presented results indicate that (PhSe)(2) exerts protective effects on SNP-induced oxidative damage in human blood components and in rat brain. These phenomena seem to be related to its thiol peroxidase-like activity and to a possible direct interaction with SNP and derivatives. Based on our results and on literature, diphenyl diselenide can be pointed as a promising antioxidant molecule.

Neurological symptoms are common in patients with glutaric acidemia type I (GA-I). Although the pathophysiology of this disorder is not yet fully established, 3-hydroxyglutaric acid (3-HGA), which accumulates in affected patients, has recently been demonstrated to be excitotoxic to embryonic chick and neonatal rat neurons probably via NMDA glutamate receptors. In the present study, we investigated the in vitro effects of 3-HGA on the [ 3 H ]glutamate and [ 3 H ]MK-801 (dizocilpine) binding to rat synaptic plasma membranes from cerebral cortex of young rats in order to elucidate the interactions of 3-HGA with glutamate receptors and its possible contribution to the in vitro excitotoxic properties of 3-HGA. 3-HGA (10–100 μM) significantly decreased Na+-dependent (up to 62%) and Na+-independent (up to 30%) [ 3 H ]glutamate binding to synaptic membranes, reflecting a possible competition between glutamate and 3-HGA for the glutamate transporter and receptor sites, respectively. Since a decrease in Na+-independent glutamate binding might represent an interaction of 3-HGA with glutamate receptors, we next investigated whether 3-HGA interacts with NMDA receptors by adding NMDA alone or combined with 3-HGA and measuring Na+-independent [ 3 H ]glutamate binding to synaptic membranes (binding to receptors). We verified that 3-HGA and NMDA, at 10 and 100 μM concentrations, decreased glutamate binding by up to 20 and 45%, respectively, and that the simultaneous addition of both substances did not provoke an additive effect, implying that they bind to NMDA receptors at the same site. Furthermore, the binding of the NMDA-channel blocker [ 3 H ]MK-801 was significantly increased (approximately 32–40%) by 10 and 100 μM 3-HGA, implying that 3-HGA was able to open the NMDA channel allowing MK-801 binding, which is a characteristic of NMDA agonists. On the other hand, glutamate had a much higher stimulatory effect on this binding (180% increase), reflecting its strong NMDA agonist property. Furthermore, the simultaneous addition of 3-HGA and glutamate provoked an additive stimulatory effect on [ 3 H ]MK-801 binding to the NMDA receptor. These data indicate that, relatively to glutamate, 3-HGA is a weak agonist of NMDA receptors. Finally, we demonstrated that 3-HGA provoked a significant increase of extracellular calcium uptake by cerebral cortex slices, strengthening therefore, the view that 3-HGA activates NMDA receptors. The present study therefore, demonstrates at the molecular level that 3-HGA modulates glutamatergic neurotransmission and may explain previous findings relating the neurotoxic actions of this organic acid with excitotoxicity.

BACKGROUND The effects of the aqueous seed extract of Syzygium cumini (ASc) in a short-term model of diabetes in rats are little explored. The present study was designed to evaluate the effect of the ASc on adenosine deaminase (ADA) activity and on biochemical and histopathological parameters in diabetic rats. METHODS ASc (100 mg/kg) was administered for 21 days in control and streptozotocin (STZ)-induced (60 mg/kg) diabetic rats. ADA activity, lipoperoxidation (cerebral cortex, kidney, liver and pancreas) and biochemical (serum) and histopathological (pancreas) parameters were evaluated. RESULTS The main findings in this short-term model of Diabetes mellitus (DM) were that the ASc (i) significantly reverted the increase of ADA activity in serum and kidney; (ii) ameliorated the lipoperoxidation in the cerebral cortex and pancreas of the diabetic group; (iii) demonstrated hypolipidemic and hypoglycemic properties and recovered the liver glycogen; and iv) prevented the HOMA-IR index increase in the diabetic group. Therefore, the ASc can be a positive factor for increasing the availability of substrates with significant protective actions, such as adenosine. Moreover, by maintaining glycogen and HOMA-IR levels, the extract could modulate the hyperglycemic state through the direct peripheral glucose uptake. CONCLUSIONS Our data revealed that the short-term treatment with ASc has an important protective role under pathophysiological conditions caused by the early stage of DM. These results enhance our understanding of the effect of the ASc on the purinergic system in DM.

Hypoxic-ischemic (HI) injury perinatal brain is a major contributor to morbidity and mortality to infants and children. Adenosine may play a role in the pathophysiology of HI, since it modulates the inflammatory process and the release of several neurotransmitters. Thus, the aim of this study was to identify the isoforms of adenosine deaminase (ADA) responsible for the enzymatic activity as well as the adenosine kinase (ADK) and A1 adenosine receptor (A1R) expression in the cerebral cortex eight days after HI. Myeloperoxidase (MPO) and N-acetyl-glucosaminidase (NAG) were assessed as inflammation markers. ADA activity was analyzed, in the presence or absence of a specific ADA1 inhibitor, erythro-9-(2-hydroxy-3-nonyl) adenine. The ADA1 activity (92.6%) was significantly higher than ADA2 (7.4%) activity in the cerebral cortex eight days after HI. A1Rs and ADK protein expression showed decreased 8 days after insult. Interestingly, the ADA1, MPO, and NAG activities were correlated positively. In view of this, we conclude that the inhibitor of ADA1, in in vitro conditions, was effective in decreasing the ADA activity, and that mainly ADA1 isoform is responsible for the increase in the ADA activity 8 days after HI insult. Therefore, HI neonatal was able to alter the ADK and A1R expression. Thus, due to the importance of adenosine signaling in the regulation of inflammatory and immune process and the crucial role of ADA in the postischemic homeostase of adenosine as well as during inflammatory process, we suggest that ADA1 inhibitors may play an important role in the regulation of events that follow the HI insult, favoring the increase in the adenosine in the sites of tissue injury. Together, these results highlight a role of the purinergic signaling cascade in the pathophysiology of HI neonatal.

Background Obesity is the hallmark of the metabolic syndrome representing a major global health problem. It is considered a state of chronic inflammation with minimal exploration of salivary biomarkers. Thus, the intent of the present study was to assess the activities of salivary dipeptidyl peptidase IV (DPP-IV), adenosine deaminase (ADA) and lipid peroxidation in obese young and overweight young subjects. Methods ADA, DPP-IV activities and lipid peroxidation were investigated in saliva, as well as insulin, glucose, HbA1c, HOMA and anthropometric measurements in 149 young adults, including 54 with normal weight, 27 overweight and 68 obese subjects. Results Salivary ADA and DPP-IV activities as well as lipid peroxidation were higher in patients with obesity compared to the normal weight group. Correlations between ADA/DPP-IV activities, lipid peroxidation/ADA activity, ADA activity/hip circumference and BMI/weight were observed. Conclusions Our results indicate that the increase in the salivary ADA and DPP-IV activities as well as in the lipid peroxidation could be related of the regulation to various aspects of adipose tissue function and inflammatory obesity. It is suggested that these salivary biomarkers may be used as biochemical test in clinical abnormalities present in obesity, in the absence of oral inflammatory diseases.

This study examines the effect of new 1,5 benzodiazepines on acetylcholinesterase (AChE) and ATPDase (apyrase) activities from cerebral cortex of adult rats. Simultaneously, the effects of the classical 1,4-benzodiazepine on these enzymes were also studied for comparative purpose. The compounds 2-trichloromethyl-4-phenyl-3H-1,5-benzodiazepin and 2-trichloromethyl-4-(p-methyl-phenyl)-3H-1,5-benzodiazepin significantly inhibited acetylcholinesterase activity (p < 0.01) when tested in the range of 0.18–0.35 mM. The inhibition caused by these two new benzodiazepines was noncompetitive in nature. Similarly, at concentrations ranging from 0.063 to 0.25 mM, the 1,5 benzodiazepines inhibited ATP and ADP hydrolysis by synaptosomes from cerebral cortex (p < 0.01). However, the inhibition of nucleotide hydrolysis was uncompetitive in nature. Our results suggest that, although diazepam and the new benzodiazepines have chemical differences, they both presented an inhibitory effect on acetylcholinesterase and ATPDase activities.

Syzygium cumini (S. cumini) is a plant known for its antidiabetic properties. The aim of this study was to evaluate the effect of Sc aqueous leaf extract (ASc) on adenosine deaminase (ADA) activity in erythrocytes (RBCs) exposed to high glucose concentrations (30 mM) in vitro. We also investigated the effects of the main phenolic compounds found in ASc (gallic acid, rutin, and chlorogenic acid) and the effects of insulin, caffeine, and dipyridamole, which are substances involved in the adenosine metabolism, on ADA activity in vitro. Blood samples were obtained from healthy volunteers and a suspension of RBCs was used for the determination of ADA activity. The results showed that: (1) the effect of ASc on ADA activity was more significant than the combination of phenolic compounds; (2) insulin, caffeine, or dipyridamole prevented high glucose increase of ADA activity at doses as low as 50 μU/mL, 25 μM, and 1 μM, respectively; (3) the inhibitory effect caused by ASc on erythrocyte ADA activity remained practically the same after the combination of the extract with insulin or caffeine; (4) when RBCs were exposed to ASc plus dipyridamole, this chemical attenuated the effect of ASc on ADA activity, suggesting an antagonism or a competition with ASc by the same site of action. Therefore, ASc was more effective in preventing the increase in ADA activity than phenolic compounds, suggesting that ASc may collaborate to improve endothelial dysfunction, antioxidant, anti-inflammatory, and antithrombotic properties of adenosine by affecting its metabolism. The results of this study help to provide evidence of the empirically supported benefits of the use of S. cumini in diabetes.

Syzygium jambos and Solanum guaraniticum are both employed in Brazil as medicinal plants, even though their potential toxicity is not well established and they are frequently misused. The aim of this study was investigate the effect of the aqueous leaf extracts of both plants on δ-aminolevulinate dehydratase (δ-ALA-D) and acetylcholinesterase (AChE) activities and the antioxidant action against oxidative damage induced by sodium nitroprusside in rats, using in vitro assays. In addition, the presence of gallic, caffeic and chlorogenic acids, as well as rutin, quercetin and kaempferol as bioactive compounds in the extracts was identified by HPLC and their levels quantified. The antioxidant activities of both extracts were assessed by their capabilities to scavenge nitric oxide and to inhibit lipid peroxidation. Only Syzygium jambos presented thiol-peroxidase-like activity. Although neither extract affected the AChE activity, the aqueous extract of Solanum guaraniticum inhibited brain δ-ALA-D activity, suggesting a possible impairment effect on the central nervous system. Our results showed that both extracts exhibited efficient free radical scavenger activity and are an interesting source of bioactive compounds, justifying their use in folk medicine, although Solanum guaraniticum extract could have neurotoxicity properties and we therefore suggest that its use should be restricted to ensure the health of the population.

Introduction: Tuberculosis (TB) is a major global health problem and requires special attention from health professionals and society as a whole. Among the extrapulmonary forms, pleural TB stands out as the most common cause of pleural effusion (PE). To perform a differential diagnosis between tuberculous and non-tuberculous PE is a critical clinical problem, since the conventional methods are not always useful in diagnosis, because they present limitations. Adenosine deaminase (ADA) is an enzyme found mainly in lymphocytes, directly related to the activation of these cells and plays an important role in the immune system. Objective: To verify the activity of ADA in pleural effusion of patients treated at the University Hospital of Santa Maria, to aid in the diagnosis of pleural TB, as well as the relationship of the enzyme with biochemical parameters routinely performed in pleural fluid as protein, glucose and lactate dehydrogenase activity (LDH). Methods: Through a retrospective study, it was analyzed 200 medical records of patients admitted with pleural effusion from December 2008 to December 2011. Statistical analyses was performed by non-parametrical tests, Kruskal - Wallis and Pearson correlation, the data were expressed as median (25% e 75% percentis) and a p value

BACKGROUND We assessed plasma malondialdehyde (MDA) levels as a biomarker of lipid peroxidation in type 2 diabetic patients on insulin therapy. Associations among MDA levels and some risk factors for the development of chronic complications of diabetes were also evaluated. METHODS MDA, fasting glucose, fructosamine, urinary albumin, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, creatinine, uric acid, serum albumin, lactate, high sensitive C reactive protein (hsCRP), and vitamin E were measured in 53 type 2 diabetic patients and 26 healthy subjects. RESULTS MDA levels were higher in type 2 diabetes insulin users (12.8 +/- 3.0 micromol/L) and type 2 diabetes no insulin users (10.3 +/- 2.1 micromol/L) compared to control subjects (8.2 +/- 2.1 micromol/L). Fasting glucose, fructosamine, urinary albumin, and hsCRP were higher in all type 2 diabetic patients compared to controls. Significant correlations were observed between MDA and fasting glucose (r = 0.685, p < 0.001), fructosamine (r = 0.526, p < 0.001), urinary albumin (r = 0.516, p < 0.001), and the duration of type 2 diabetes (r = 0.401, p = 0.005). CONCLUSIONS MDA levels increased in type 2 diabetes, especially in patients on insulin therapy. Chronic hyperglycemia and other biomarkers, such as urinary albumin, were correlated with MDA levels, suggesting the involvement of lipid peroxidation in the pathogenesis of diabetes complications.

Perinatal hypoxic-ischemic (HI) brain injury is a common problem with severe neurologic sequelae. The definitive brain injury is a consequence of pathophysiological mechanisms that begin at the moment of HI insult and may extend for days or weeks. In this context, the inflammatory response and the formation of reactive oxygen species seem to play a key role during evolution of brain damage after injury. Thus, the aim of this study was to describe the chronological sequence of acetylcholinesterase (AChE) activity and the lipid peroxidation changes in the cerebral cortex using the classic model of neonatal HI. Furthermore, the erythrocyte AChE and adenosine deaminase (ADA) activities as well as the serum levels of proinflammatory cytokines were assessed. We observed that neonatal HI caused an increase of lipid peroxidation immediately after HI insult, which remained for several days afterward. There was a time-related change in the AChE activity in the cerebral cortex and the same was observed in erythrocyte AChE and ADA activities. In addition, immediately after HI, ADA activity showed a strong positive correlation with all proinflammatory cytokines assessed. Together, these findings may help the understanding of some mechanism related to the pathophysiology of neonatal HI, therefore highlighting the putative therapeutic targets to minimize brain injury and enhance recovery.

The aim of this study was to evaluate the inflammatory and oxidative biomarkers’ levels in obese subjects and their associations with body mass index (BMI), in order to investigate the role of these biomarkers in obesity. Fasting glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, apolipoprotein A, apolipoprotein B, albumin, urinary albumin, creatinine, glomerular filtration rate, interleukin-6 (IL-6), nitrate/nitrite (NOx), and ischemia-modified albumin (IMA) were measured in 93 subjects divided according to different BMI. IL-6, urinary albumin, and IMA levels were significantly higher in obese subjects. However, the levels of NOx were significantly lower in this population. Significant correlations between BMI and IL-6 (r = 0.326, P = 0.002), NOx (r = −0.249, P = 0.021), urinary albumin (r = 0.270, P = 0.008), and IMA (r = 0.286, P = 0.005) were reported. We have shown an increase of IL-6, urinary albumin, and IMA combined with lower levels of NOx in obese patients and an association between of these biomarkers with BMI, suggesting a possible interplay of oxidative stress, inflammation, and endothelial dysfunction state in obesity.

Metabolic syndrome (MetS) is considered a state of chronic inflammation. This study aimed to ascertain selected parameters of purinergic and cholinergic systems related to glucose metabolism and inflammation, as well as (γ)-glutamyltransferase (GGT) and N-acetyl-b-glucosaminidase (NAG) activities and lipoperoxidation in lymphocytes of patients with MetS.The adenosine deaminase (ADA), dipeptidyl peptidase IV (DPP-IV), acetylcholinesterase (AChE), GGT and NAG activities, as well as thiobarbituric acid reactive substances (TBARS) levels were investigated in lymphocytes of patients with MetS (n=38) and healthy volunteers (n=41). We also evaluated the insulin levels, anthropometric measurements and routine biochemical analyses.ADA (p0.05), DPP-IV and AChE (p0.0001) activities were higher in patients with MetS when compared to the control group. Furthermore, we observed correlations between ADA and DPP-IV activities (p=0.0002; r=0.5945), TBARS levels and ADA (p=0.0021; r=0.5172) and DPP-IV activities (p=0.0022; r=0.5010).Our findings showed that MetS might cause tissue distress that disturbed lymphocytic ADA, DPP-IV and AChE activities in response to inflammatory stimuli. These alterations evidence clinical abnormalities, since these enzymatic systems are able to regulate several aspects of adipose tissue function and inflammatory state of MetS and could be used successfully both for preventing and for halting the progression of MetS.

To assess the effect of hypertension on δ-aminolevulinate dehydratase (δ-ALA-D) activity of type 2 diabetic patients (T2DM).δ-ALA-D activity and reactivation index, as well as markers of oxidative stress, biochemical and anthropometrics parameters were determined in T2DM (n=23), type 2 diabetic patients with hypertension (T2DM/HT) (n=30) and controls (n=30).T2DM/HT presented a greater inhibition of δ-ALA-D activity, a higher reactivation index (p0.05) and a greater depletion of plasma protein thiol groups (P-SH) when compared to T2DM. Moreover, δ-ALA-D activity was positively associated with SH groups and negatively associated with serum protein carbonyl (PC) while its reactivation index was negatively associated with SH groups and positively associated with PC.These results point out that there is a possible interference of hypertension on the mechanism of the δ-ALA-D activity suggesting that this condition aggravated the oxidative stress of diabetes mellitus.

Immune response and inflammation were suggested to play certain roles in the development and complications of type 2 diabetes mellitus. The main objective of this study was to investigate the CD26 expression and its relationship with adenosine deaminase (ADA), dipeptidyl peptidase IV (DPP-IV), γ-glutamyltransferase (GGT), and N-acetyl-β-glucosaminidase (NAG) activities in lymphocytes of type 2 diabetics (T2DM) patients. These parameters were assessed in 25 T2DM patients and 20 control subjects. We observed a decrease in CD26 expression and a significant increase in the ADA activity in T2DM patients when compared with control subjects. There were no differences between activities of DPP-IV, NAG, and GGT in lymphocytes of T2DM patients and control subjects. Meanwhile, a significant negative correlation was observed between CD26 expression and DPP-IV activity in lymphocytes of T2DM patients. Moreover, a positive correlation was found between DPPIV and ADA activities. The results suggest that the reduction of CD26 expression may be associated in the regulation of DPP-IV in T2DM patients.

The aim of the present study was to investigate the effect of curcumin (Cur) on the activity of ectonucleoside triphosphate diphosphohydrolase (CD39), 5'-nucleotidase (CD73) and adenosine deaminase in platelets of cigarette smoke-exposed rats. For that purpose, we subjected male Wistar rats to a treatment with Cur and cigarette smoke, once a day, 5 days each week, for 30 days. The rats were treated by gavage with Cur or corn oil and then exposed to cigarette smoke. The experimental procedures were divided into two sets of experiments. In the first, the animals were divided into four groups: vehicle (corn oil) or Cur 12·5, 25 or 50 mg·kg(-1) . In the second, the animals were divided into five groups: vehicle (corn oil), smoke, or smoke and Cur 12·5, 25 or 50 mg·kg(-1) . The results showed that treatment with Cur significantly prevented the increased adenosine triphosphate (ATP) (121%) and adenosine monophosphate (AMP) (159%) and the decreased adenosine diphosphate (ADP) (51%) hydrolysis observed in the cigarette smoke-exposed rats Our results suggest that those purinergic enzyme alterations observed in the cigarette smoke-exposed rats could be related to an excessive platelet aggregation and point toward the potential of Cur to modulate purinergic signalling and, consequently, regulate the thrombus formation.