Curcumin modulates neurogliogenesis and purinergic receptor expression in neural precursor cells infected with Toxoplasma gondii.

Toxoplasma gondii is an obligate intracellular parasite that causes toxoplasmosis, and its congenital transmission is of paramount concern. During embryonic development, infection with the parasite causes irreversible damage to the still-forming fetus's central nervous system (CNS). In the pathogenesis of neurotoxoplasmosis, purinergic receptors prejudice neuroprotection, neuroinflammation, and activation of microbicide mechanisms against the parasitic vacuole. This study used curcumin as a treatment for neural precursor cells (NPCs) infected with T. gondii. The congenital toxoplasmosis induction consisted of maternal infection with the VEG strain, and NPCs were obtained from the telencephalon of mouse embryos. Curcumin at increasing concentrations was administered in vitro to analyze NPC metabolic activity, cell number, and size, as well as neurogliogenesis, proving to be effective in recovering the size of infected NPCs. Curcumin partially re-established impaired neurogenesis. Purinergic A1, A2A, and P2X7 receptors may be related to neuroprotection, neuroinflammatory control, and activation of mechanisms for inducing the parasite's death. ERK 1/2 was highly expressed in infected cells, while its expression rates decreased after the addition of the treatment, highlighting the possible anti-inflammatory action of curcumin. These findings suggest that curcumin treats neurological perturbations induced by toxoplasmosis.

Impact of free curcumin and curcumin nanocapsules on viability and oxidative status of neural cell lines.

Curcumin is an active polyphenol substance found in the highest concentrations in the roots of Curcuma longa. Its health benefits have led to recent increases in the consumption of curcumin. It has anti-inflammatory and antioxidant activities and is a potent neuroprotective against diseases of the brain. Nevertheless, its low bioavailability and its relative difficulty crossing the blood-brain barrier limit curcumin's use for these purposes. Curcumin-loaded nanoparticles may be an effective treatment for several diseases although there is a paucity of studies reporting its safety in the central nervous system (CNS). Therefore, this study aimed to identify non-neurotoxic concentrations of free curcumin and two nanoformulations of curcumin. Cell lines BV-2 and SH-SY5Y, both originating from the CNS, were evaluated after 24, 48, and 72 h of treatment with free curcumin and nanocapsules We measured viability, proliferation, and dsDNA levels. We measured levels of reactive oxygen species and nitric oxide as proxies for oxidative stress in culture supernatants. We found that free curcumin was toxic at 10 and 20 µM, principally at 72 h. Nanoformulations were more neurotoxic than the free form. Safe concentrations of free curcumin are between 1-5 µM, and these concentrations were lower for nanoformulations. We determined the ideal concentrations of free curcumin and nanocapsules serving as a basis for studies of injuries that affect the CNS.

Berberine increases the expression of cytokines and proteins linked to apoptosis in human melanoma cells.

BACKGROUND: Melanoma is the most lethal form of skin cancer, and its incidence has increased considerably in the last decades. Melanoma presents difficult treatment with strong resistance of tumor cells, due to its extremely invasive nature with high capacity to metastases. Berberine (BBR), an isoquinoline alkaloid, is a molecule found in several medicinal plants, and has been studied in several diseases, demonstrating antimicrobial, antidiabetic and anti-inflammatory properties and anti-tumorigenic effects. METHODS AND RESULTS: In SK-MEL-28 cells, 50 µM BBR treatment for 24 h decreased cell viability by 50 percent. This concentration generated cell death both by early apoptosis and necrosis, with an increase in the DNA damage index. BBR increased (*p < 0.05) the proportion of cells in G1/G0 phase and decreased (###p < 0.005) the percentage of cells in S phase. The alcaloid increased (****p < 0.001) ROS production compared to untreated controls with an increase in activated caspase 3 and phosphorylated p53 protein levels. In addition, BBR significantly enhanced ERK as well as both pro- and anti-inflammatory cytokine expression compared to untreated controls. CONCLUSIONS: BBR has important antiproliferative effects and may be alone or in adjunct therapy a promising candidate for melanoma treatment, a cancer with great incidence and high lethality.

Feed supplementation with inulin on broiler performance and meat quality challenged with Clostridium perfringens: Infection and prebiotic impacts.

Following the ban on the use of antibiotics as growth enhancers in 2006 by the European Union, alternative products have been sought. Inulin is a prebiotic that is found naturally in many plants. It reaches large intestine of animals unaltered, where it is fermented by beneficial bacteria that comprise the intestinal microbiota. Inulin also inhibits the growth of pathogenic bacteria. Consumption of inulin in chicken diets improves performance at slaughter; nevertheless, little is known about its effects on poultry meat. Therefore, the objective of this study was to evaluate the effects of inulin on feeding of broilers challenged with Clostridium perfringens (4.0 × 108 CFU) and its consequences on the quality of breast meat. Four hundred Cobb male broiler chickens were distributed in a completely randomized design with four treatments and five replications each, as follows: T1: control treatment, basal diet (DB); T2: DB + 21-day challenged with C. perfringens orally; T3: DB + 21-day challenge with C. perfringens orally +25 mg/kg inulin; T4: DB + 21-day challenge by C. perfringens orally +4.4 mg/kg lincomycin. There were no significant differences between treatments in terms of pH, color parameters (L, a*, b*), water retention capacity, or shear force cooking weight loss. However, we found that the meat of poultry challenged by C. perfringens showed lower lipid peroxidation and increased activity of the antioxidant enzymes SOD and CAT, suggesting improvement in antioxidant profile. Nitrate/nitrite levels were lower with T3 and higher with T4 than with T1. We therefore conclude that inulin can replace antibiotics as growth promoters without causing changes in the physicochemical characteristics of meat. C. perfringens challenge caused lower lipid peroxidation and stimulated antioxidant responses in breast meat.

Impacts of Escherichia coli infection in young breeder chicks on the animal behavior and cerebral activity of purinergic and cholinergic enzymes involved in the regulation of molecules with neurotransmitter and neuromodulator function.

The objective of this study was to evaluate if infection by Escherichia coli in juvenile breeder chicks alters the activity of enzymes involved in neurotransmission and cerebral immunomodulation, including acetylcholinesterase (AChE), nucleoside triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase (5'NT) and adenosine deaminase (ADA), as well as their effects on the pathogenesis of the disease. We divided 20 growing breeder chicks into two groups (n = 10 per group). One group was experimentally infected with 1 mL of culture medium containing 1 × 108 CFU of E. coli intraperitoneally. The other was the negative control. On the tenth day after infection, the animals were euthanized and brain samples were collected. Macroscopically, pericarditis and hepatic congestion were observed in the birds, but without histopathological lesions in the encephalon although the bacterium was present in the cerebral cortex of all animals in the infected group (i.e., they were PCR-positive). The activity of AChE, NTPDase, 5'-NT and ADA were evaluated in the cerebral homogenates of the birds after 10 days of infection. AChE activity in the cerebral cortex was lower in the infected group than in the control; there was an increase in the activity of NTPDase, 5'-nucleotidase and ADA, possibly indicating greater hydrolysis of ATP (P < 0.001), ADP (P < 0.01) and AMP (P < 0.01), followed by increased adenosine deamination (P < 0.001). Despite these changes, no apparently diseased animals were observed throughout the experimental period. Therefore, such changes in enzymatic activity may affect the functioning of the central nervous system because these enzymes are responsible for extracellular regulation of molecules that act on neurotransmission and immunomodulation such as acetylcholine, ATP and adenosine.

Berberine induces apoptosis in glioblastoma multiforme U87MG cells via oxidative stress and independent of AMPK activity.

Glioblastoma multiforme (GM) is the most prevalent tumor among gliomas and presents the highest mortality rate among brain tumors. Berberine (BBR) is an alkaloid isoquinoline found in medicinal plants such as Coptis chinensis. Studies have been showed that BBR presents protective activity in mesenchymal cells and neurons, and antitumor properties in breast cancer and hepatocarcinoma. The aim of this study was to investigate the antitumor effects of BBR in GM U87MG cells, as well as to identify, whether such effects are mediated by oxidative stress and canonical apoptotic pathways. After treatment with several concentrations of BBR (10, 25, 100 and 250 µM) for 24, 48 and 72 h of exposure, BBR reduce cell viability of U87MG cells in a concentration- and time-dependent manner. Afterwards, it was observed that BBR, starting at a concentration of 25 µM of 24 h exposure, significantly suppressed proliferation and increased early apoptosis (53.5% ± 11.15 of annexin V+ propidium iodide- cells) compared to untreated cells (7.5% ± 4.6). BBR-induced apoptosis was independent from AMPK activity and did not change total caspase-3 and p-p53 levels. Moreover, BBR (25 µM/24 h) increased oxidative stress in U87MG cells, evidenced by high levels of reactive oxygen species, thiobarbituric acid reactive substance and protein carbonylation. Considering the antitumor effects of BBR in U87MG cells, this compound may be a potential candidate for adjuvant GM treatment.

1α, 25-Dihydroxyvitamin D3 alters ectonucleotidase expression and activity in human cutaneous melanoma cells.

PURPOSE: We hypothesized that vitamin D decreases rates of adenosine formation in human cutaneous melanoma cells through the inhibition of extracellular adenosine 5'-triphosphate breakdown, thereby affecting tumor cell viability. Therefore, the objective of this study was to explore the mechanisms of action of 1α, 25-dihydroxyvitamin D3 (1,25(OH)2 D3) on the activity and expression of ectonucleotidases in cutaneous melanoma cells. METHODS: A human melanoma cell line, SK-Mel-28, was treated with 1 to 50 nM of the active vitamin D metabolite (1,25(OH)2 D3) over 24 hours, followed by determination of NTPDase1/CD39 and ecto-5'-nucleotidase/CD73 activity and expression rates of the purinergic system-related NTPDASE1, NT5E and adenosine deaminase and vitamin D receptor. An 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay was used to evaluate cellular viability. RESULTS: 1,25(OH)2 D3 decreased adenosine monophosphate hydrolysis via ecto-5'-nucleotidase/CD73 and expression of CD73, but did not change NTPDase1/CD39 activity; it increased the CD39 expression. We also observed an increase of cell viability at 1 nM, but this viability decreased as the concentrations of vitamin D active metabolite increased to 50 nM. There were no differences in gene expression levels. CONCLUSION: To the best of our knowledge, we showed for the first time a mechanism of control of adenosine production via modulation of the purinergic system in cutaneous melanoma cells treated with the active metabolite of vitamin D. This study provides original information regarding mechanisms, in which vitamin D plays a key role in preventing tumor progression in human melanoma cells.

Physical exercise prevents alterations in purinergic system and oxidative status in lipopolysaccharide-induced sepsis in rats.

Sepsis is a generalized infection that involves alterations in inflammatory parameters, oxidant status, and purinergic signaling in many tissues. Physical exercise has emerged as a tool to prevent this disease because of its anti-inflammatory and antioxidant properties. Thus, in this study, we investigated the effects of physical exercise on preventing alterations in purinergic system components, oxidative stress, and inflammatory parameters in lipopolysaccharide (LPS)-induced sepsis in rats. Male Wistar rats were divided into four groups: control, exercise (EX), LPS, and EX+LPS. The resisted physical exercise was performed for 12 weeks on a ladder with 1 m height. After 72 hours of the last exercise session, the animals received 2.5 mg/kg of LPS for induction of sepsis, and after 24 hours, lungs and blood samples were collected for analysis. The results showed that the exercise protocol used was able to prevent, in septic animals: (1) the increase in body temperature; (2) the increase of lipid peroxidation and reactive species levels in the lung, (3) the increase in adenosine triphosphate levels in serum; (4) the change in the activity of the enzymes ectonucleotidases in lymphocytes, partially; (5) the change in the density of purinergic enzymes and receptors in the lung, and (6) the increase of IL-6 and IL-1ß gene expression. Our results revealed the involvement of purinergic signaling and oxidative damage in the mechanisms by which exercise prevents sepsis aggravations. Therefore, the regular practice of physical exercise is encouraged as a better way to prepare the body against sepsis complications.

Superoxide-hydrogen peroxide imbalance differentially modulates the keratinocytes cell line (HaCaT) oxidative metabolism via Keap1-Nrf2 redox signaling pathway.

The purpose of this study was to investigate the effect of a superoxide-hydrogen peroxide (S-HP) imbalance of the superoxide dismutase manganese dependent (SOD2) gene, generated by paraquat and porphyrin exposure, on the keratinocytes cell line (HaCaT) oxidative metabolism. Paraquat acts increasing superoxide (O2·-) levels, while porphyrin increases hydrogen peroxide (H2O2) levels, acting as VV-SOD2-like and AA-SOD2-like molecules, respectively. First of all, HaCAT cells were treated with different concentrations of paraquat and porphyrin (1; 10; 30, and 70 µM) to determine the concentration of both that causes imbalance. After defining the concentration of paraquat and porphyrin (70 µM), a time curve was performed (1, 3, 6, and 24 h) to evaluate ROS production levels. Other oxidative parameters, such as nitric oxide (NO), lipoperoxidation (TBARS) and protein carbonyl, were evaluated after 24 h of incubation, as well as genotoxic analyses, apoptosis detection, and gene expression. Our findings revealed that paraquat exposure decreased cell viability, increasing lipoperoxidation, DNA damage, and apoptosis. On the other hand, porphyrin treatment increased cell viability and proliferation, ROS and NO production, triggering protein and DNA damage. In addition, porphyrin up-regulated Keap1 and Nrf2 gene expression, while paraquat decreased Nrf2 gene expression. In this sense, we suggested that the superoxide-hydrogen peroxide imbalance differentially modulates oxidative stress on keratinocytes cell line via Keap1-Nrf2 gene expression pathway.

Antiproliferative and apoptotic effects of caffeic acid on SK-Mel-28 human melanoma cancer cells.

Cutaneous melanoma (CM) is an extremely aggressive cancer presenting low survival and high mortality. The vast majority of patients affected by this disease does not respond or show resistance to the chemotherapeutic drugs, which makes the treatment ineffective. In this sense, the necessity for the development of new agents to assist in CM therapy is extremely important. One of the sources of great interest in this search are compounds of natural origin. Among these compounds, caffeic acid has demonstrated a broad spectrum of pharmacological activities as well as antitumor effects in some types of cancer. Therefore, the objective of this work was to investigate the possible antitumor effect of caffeic acid on the SK-Mel-28 cell line, human CM cells. Cells were cultured in flasks with culture medium containing fetal bovine serum, antibiotic, and antifungal, and maintained in ideal conditions. Cells were treated with 25 µM, 50 µM, 100 µM, 150 µM and 200 µM of caffeic acid and dacarbazine at 1 mg/mL. We verified the effect on cell viability and cell death, apoptosis, cell cycle, colony formation and gene expression of caspases. Results showed a decrease in cell viability, cell death induction by apoptosis, inhibition of colony formation, modulation of cell cycle and alterations in gene expression of caspases after caffeic acid treatment. These results suggest an antitumor effect of the compound on SK-Mel-28 cells. This study provides original information on mechanisms by which caffeic acid may play a key role in preventing tumor progression in human melanoma cells.

High-intensity intermittent exercise increases adenosine hydrolysis in platelets and lymphocytes and promotes platelet aggregation in futsal athletes.

Acute bouts of high-intensity intermittent exercise (HIIE) or sports are associated with changes in lymphocytes and platelet functions and we hypothesized that the purinergic system is involved with these alterations. We investigated the activity of ectonucleotidases in platelets and lymphocytes as well as the platelet aggregation of futsal players in response to an acute protocol of HIIE. Thus, 19 male semi-professional futsal players were submitted to 40 min of HIIE on a treadmill. Blood samples were collected three-time points: before exercise, immediately after, and 30 min after the end of the session. Platelet-rich plasma (PRP) and lymphocytes were isolated. ATP, ADP, AMP, and adenosine hydrolysis, NTPDase1 (CD39) expression as well as platelet aggregation were measured. Our results showed HIIE induced a decrease in ATP and ADP hydrolysis in platelets, an increase in adenosine hydrolysis and an increase in platelet aggregation immediately after exercise. After 30 min of recovery, enzymatic activity and platelet aggregation returned to baseline levels. In lymphocytes, adenosine hydrolysis was augmented immediately after exercise and remained increased even after 30 min of recovery. In conclusion, acute HIIE triggers a transient proaggregant status that is reverted after a 30 min of recovery. The effects of HIIE in lymphocytes remained after 30 min of recovery, indicating a pro-inflammatory response. This work elucidated some of the mechanisms by which purinergic system regulates lymphocytes and platelets activities related to HIIE, suggesting that the type of exercise may influence an increase in platelet aggregation even in trained individuals.

High levels of extracellular ATP lead to chronic inflammatory response in melanoma patients.

Skin cancer represents a serious public health problem and melanoma is considered the most significant due to its high metastasis capacity. Evasion mechanisms are the main characteristic of these tumor cells to escape of immune response. Extracellular nucleotides and nucleosides play an important role in inflammatory and immune responses. In this study, we analyzed the expression and activity of purinergic system enzymes in platelets and lymphocytes, ATP levels quantification, as well the level of pro and anti-inflammatory interleukins in the serum of 23 patients with surgical melanoma removal (CM group) and 23 control subjects (CT group). Results showed a decrease in ATP, ADP, and AMP hydrolysis and an increase in ATP levels quantification in CM group. The pro-inflammatory cytokines were elevated in CM group when compared to CT group. These results suggest an inflammatory process, even after surgical removal, due to elevated extracellular ATP levels. Besides, CM group displayed an increase in IL-10 levels and an increased in ADA activity in platelets and lymphocytes. Once adenosine and IL-10 are anti-inflammatory molecules, these results indicate a down-regulation of immune system front to malignant process. The alteration in nucleotide and nucleoside hydrolysis reinforces the purinergic systems role in this cancer. Therefore, even after surgical removal, the purinergic system can develop a chronic inflammatory micro-environment that can influence directly on relapse or metastasis.

A prophylactic protocol to stimulate the immune response also controls infectious disease and, consequently, minimizes diarrhea in newborn heifers.

The immunostimulatory and immunomodulatory properties of selenium (Se), an essential trace element for animals, has increase its use because may prevent/or reduce the occurrence of infectious diseases. Thus, the aim of this study was to verify whether Se and vitamins (A and E) applied via subcutaneous associated with secnidazole via oral exert positive effects in the antioxidant and immune systems, as well as whether prevent infections caused by protozoan and bacteria, and consequently, reduce the number of cases of diarrhea in heifers. Thirty-two newborn Holstein heifers were divided into two groups with sixteen animals each: the control group and the treated group that received sodium selenite (0.2 mg/kg) and vitamins A (35 mg/kg) and E (1 mg/kg) with one day of life, and a second application associated with secnidazole (400 mg/animal) on day 10 of life. Sample collection (blood and feces) were performed on days 1, 15, 30, 45 and 60 of life. Heifers from the treated group showed higher hematocrit values compared to the control group on day 60 of life, while total serum protein levels were higher on days 15 and 30. The ceruloplasmin (days 15, 30 and 60), IgG of heavy chain (days 15, 30, 45 and 60), IgG of light chain (days 45 and 60) and haptoglobin (days 15, 30, 45 and 60) were higher in the treated group compared to the control group. Serum levels of glucose decreased in treated animals on day 60 of life, while serum levels of albumin, triglycerides, urea, cholesterol, thiobarbituric acid reactive substances, reactive oxygen species and glutathione S-transferase activity did not differ between groups. Secnidazole was able to prevent infections caused by Giardia duodenalis in the first few days of life, but no difference was observed between groups. Moreover, there was no difference on total bacteria count and the incidence of diarrhea between groups. No difference on weight gain was observed on day 60 of life, but on day 210 of life treated animals had higher weight gain compared to the control group. Based on these evidences, we concluded that the injectable application of Se and vitamins (A and E) associated to secnidazole can improve the immunological system, and consequently, favor animal's performance.

Physiological changes in the adenosine deaminase activity, antioxidant and inflammatory parameters in pregnant cows and at post-partum.

The aim of this study was to evaluate the behaviour of adenosine deaminase (ADA) activity, as well as its participation in the immunomodulation of pregnant cows. Thus, sixteen cows were divided into two groups (A and B): the group A was composed by cows not pregnant (n = 8), while the group B was composed by pregnant cows (n = 8). Serum levels of interleukin-10 (IL-10), IL-6, tumour necrosis factor alpha (TNF-α), reactive oxygen species (ROS) and C-reactive protein (CRP), as well as ADA and glutathione S-transferase (GST) activities, were measured on five sampling times (3, 5, 7 and 8 months of gestation, and soon after calving). Serum ADA activity was similar throughout the experiment in the cows belonging to the group A, but its activity increased during the experiment in cows from the group B, that is it was lower in the third and fifth months of pregnancy, and higher on months 7, 8 and after calving when compared to the group A. TNF-α and IL-6 serum levels were lower in pregnant cows compared to non-pregnant animals; however, they significantly increased after calving. Serum levels of IL-10 increased after 8 months of gestation, but it reduced after calving when compared to the group A, while CRP increased on month 8 of gestation and after calving compared to the group A. Pregnant cows showed lower serum ROS levels on months 3, 5 and 7 of gestation, and higher levels at the post-partum. Serum GST activity was higher on month 5 of gestation in pregnant cows, but it was lower on months 7, 8 and in the post-partum compared to the group A. Based on these evidence, we concluded that ADA activity and the others mediators or inflammatory modulators have important role in the maintenance of cow's gestation due to their immunomodulatory effects.

Hypothyroidism Enhanced Ectonucleotidases and Acetylcholinesterase Activities in Rat Synaptosomes can be Prevented by the Naturally Occurring Polyphenol Quercetin.

Thyroid hormones have an influence on the functioning of the central nervous system. Furthermore, the cholinergic and purinergic systems also are extensively involved in brain function. In this context, quercetin is a polyphenol with antioxidant and neuroprotective properties. This study investigated the effects of (MMI)-induced hypothyroidism on the NTPDase, 5'-nucleotidase, adenosine deaminase (ADA), and acetylcholinesterase (AChE) activities in synaptosomes of rats and whether the quercetin can prevent it. MMI at a concentration of 20 mg/100 mL was administered for 90 days in the drinking water. The animals were divided into six groups: control/water (CT/W), control/quercetin 10 mg/kg, control/quercetin 25 mg/kg, methimazole/water (MMI/W), methimazole/quercetin 10 mg/kg (MMI/Q10), and methimazole/quercetin 25 mg/kg (MMI/Q25). On the 30th day, hormonal dosing was performed to confirm hypothyroidism, and the animals were subsequently treated with 10 or 25 mg/kg quercetin for 60 days. NTPDase activity was not altered in the MMI/W group. However, treatment with quercetin decreased ATP and ADP hydrolysis in the MMI/Q10 and MMI/Q25 groups. 5'-nucleotidase activity increased in the MMI/W group, but treatments with 10 or 25 mg/kg quercetin decreased 5'-nucleotidase activity. ADA activity decreased in the CT/25 and MMI/Q25 groups. Furthermore, AChE activity was reduced in all groups with hypothyroidism. In vitro tests also demonstrated that quercetin per se decreased NTPDase, 5'-nucleotidase, and AChE activities. This study demonstrated changes in the 5'-nucleotidase and AChE activities indicating that purinergic and cholinergic neurotransmission are altered in this condition. In addition, quercetin can alter these parameters and may be a promising natural compound with important neuroprotective actions in hypothyroidism.

Chronic administration of methionine and/or methionine sulfoxide alters oxidative stress parameters and ALA-D activity in liver and kidney of young rats.

High levels of methionine (Met) and methionine sulfoxide (MetO) are found in several genetic abnormalities. Oxidative stress is involved in the pathophysiology of many inborn errors of metabolism. However, little is known about the role of oxidative damage in hepatic and renal changes in hypermethioninemia. We investigated the effect of chronic treatment with Met and/or MetO on oxidative stress parameters in liver and kidney, as lipid peroxidation (TBARS), total sulfhydryl content (SH), reactive oxygen species (ROS) and enzymes activities superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and delta aminolevulinic dehydratase (ALA-D). Serum biochemical parameters were evaluated. Wistar rats were treated daily with two subcutaneous injections of saline (control), Met (0.2-0.4 g/kg), MetO (0.05-0.1 g/kg) and the association between these (Met plus MetO) from the 6th to the 28th day of life. Our data demonstrated an increase of glucose and urea levels in all experimental groups. Cholesterol (MetO and Met plus MetO) were decreased and triglycerides (MetO) were increased. SOD (MetO and Met plus MetO) and CAT (Met, MetO and Met plus MetO) activities were decreased, while GPx was enhanced by MetO and Met plus MetO treatment in liver. In kidney, we observed a reduction of SH levels, SOD and CAT activities and an increase of TBARS levels in all experimental groups. ROS levels in kidney were increased in MetO and Met plus MetO groups. ALA-D activity was enhanced in liver (MetO and Met plus MetO) and kidney (Met plus MetO). These findings help to understand the pathophysiology of hepatic and renal alterations present in hypermethioninemia.

Evaluation of mediators of oxidative stress and inflammation in patients with acute appendicitis.

CONTEXT: This study aims to explore the potential of new inflammatory markers for improving the challenging diagnosis of acute appendicitis (AA). METHODS: Levels of IL-1, IL-6, IL-8, IL-10, CRP, INF-γ, and TNF-α in serum were measured in 73 patients with AA. Oxidative stress and antioxidant enzymes were analyzed. RESULTS: Serum levels of interleukins, TNF-α, and INF-γ were significantly elevated in patients with appendicitis (p < 0.0001), except for IL-10, which presented decreased levels. There were no significant differences in SOD (p = 0.29), CAT (p = 0.19), or TBARS levels (p = 0.18), whereas protein carbonyls presented significant increase (p < 0.0001). CONCLUSION: Evaluating these biomarkers could aid in diagnosing AA.

Oxidative Profile of Patients with ST Segment Elevation Myocardial Infarction.

BACKGROUND: Patients with ST-segment elevation (STEMI) have totally occluded vessels, while patients with non-ST-segment elevation (NSTEMI) present partial vessel occlusion, which may generate different levels of Reactive Oxygen Species (ROS). Objectives: The aim of this study was to compare the oxidative profile in AMI patients with ST segment elevation and non-STEMI as well as control subjects. METHODS: This study was carried with 46 AMI patients divided into STEMI and NSTEMI. The control group consisted of 40 healthy subjects. Oxidative stress profile was evaluated analyzing carbonyl protein (PCO), lipid peroxidation (TBARS), ischemia-modified albumin (IMA), vitamin C (VIT C), superoxide dismutase (SOD) and catalase (CAT). RESULTS: Serum PCO (p < 0.001), plasma TBARS (p < 0.01), serum IMA (p < 0.0001) levels, erythrocytes CAT (p < 0.001), and SOD activities (p < 0.05) were significantly higher in STEMI patients when compared with the control group (p < 0.001). No difference in the IMA levels and oxidative stress parameters was observed between conditions of AMI. Only plasma VIT C in STEMI patients was significantly lower when compared with NSTEMI patients and control group (p < 0.001). CONCLUSIONS: Results suggest that the oxidative profile generated by STEMI and NSTEMI is similar regardless of the size of arterial occlusion generated by thrombus.

Effect of Ginger and Turmeric Rhizomes on Inflammatory Cytokines Levels and Enzyme Activities of Cholinergic and Purinergic Systems in Hypertensive Rats.

Inflammation exerts a crucial pathogenic role in the development of hypertension. Hence, the aim of the present study was to investigate the effects of ginger (Zingiber officinale) and turmeric (Curcuma longa) on enzyme activities of purinergic and cholinergic systems as well as inflammatory cytokine levels in Nω-nitro-L-arginine methyl ester hydrochloride-induced hypertensive rats. The rats were divided into seven groups (n = 10); groups 1-3 included normotensive control rats, hypertensive (Nω-nitro-L-arginine methyl ester hydrochloride) rats, and hypertensive control rats treated with atenolol (an antihypertensive drug), while groups 4 and 5 included normotensive and hypertensive (Nω-nitro-L-arginine methyl ester hydrochloride) rats treated with 4 % supplementation of turmeric, respectively, and groups 6 and 7 included normotensive and hypertensive rats treated with 4 % supplementation of ginger, respectively. The animals were induced with hypertension by oral administration of Nω-nitro-L-arginine methyl ester hydrochloride, 40 mg/kg body weight. The results revealed a significant increase in ATP and ADP hydrolysis, adenosine deaminase, and acetylcholinesterase activities in lymphocytes from Nω-nitro-L-arginine methyl ester hydrochloride hypertensive rats when compared with the control rats. In addition, an increase in serum butyrylcholinesterase activity and proinflammatory cytokines (interleukin-1 and - 6, interferon-γ, and tumor necrosis factor-α) with a concomitant decrease in anti-inflammatory cytokines (interleukin-10) was observed in Nω-nitro-L-arginine methyl ester hydrochloride hypertensive rats. However, dietary supplementation of both rhizomes was efficient in preventing these alterations in hypertensive rats by decreasing ATP hydrolysis, acetylcholinesterase, and butyrylcholinesterase activities and proinflammatory cytokines in hypertensive rats. Thus, these activities could suggest a possible insight about the protective mechanisms of the rhizomes against hypertension-related inflammation.

Dietary Supplementation of Ginger and Turmeric Rhizomes Modulates Platelets Ectonucleotidase and Adenosine Deaminase Activities in Normotensive and Hypertensive Rats.

Hypertension is associated with platelet alterations that could contribute to the development of cardiovascular complications. Several studies have reported antiplatelet aggregation properties of ginger (Zingiber officinale) and turmeric (Curcuma longa) with limited scientific basis. Hence, this study assessed the effect of dietary supplementation of these rhizomes on platelet ectonucleotidase and adenosine deaminase (ADA) activities in Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME) induced hypertensive rats. Animals were divided into seven groups (n = 10): normotensive control rats; induced (l-NAME hypertensive) rats; hypertensive rats treated with atenolol (10 mg/kg/day); normotensive and hypertensive rats treated with 4% supplementation of turmeric or ginger, respectively. After 14 days of pre-treatment, the animals were induced with hypertension by oral administration of l-NAME (40 mg/kg/day). The results revealed a significant (p < 0.05) increase in platelet ADA activity and ATP hydrolysis with a concomitant decrease in ADP and AMP hydrolysis of l-NAME hypertensive rats when compared with the control. However, dietary supplementation with turmeric or ginger efficiently prevented these alterations by modulating the hydrolysis of ATP, ADP and AMP with a concomitant decrease in ADA activity. Thus, these activities could suggest some possible mechanism of the rhizomes against hypertension-derived complications associated to platelet hyperactivity. Copyright © 2016 John Wiley & Sons, Ltd.