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The objective of this study was to determine whether the addition of grape residue flour (GRF) in the diet of suckling lambs would improve their health and consequently enhance their growth. We used 48 lambs, 30 days of age divided into four treatments with four repetitions each, with each repetition consisting of three animals. The groups were identified as follows: G-0%, used as a control (without GRF) and G-0.5%, G-1% and G-2% referring to treatment with grape residue flour in doses of 0.5%, 1%, and 2% of inclusion in the concentrate, respectively. Lambs in groups G-1% and G-2% had higher final body weights, weight gain and average daily gain (ADG) compared to the other groups. GRF dietary supplementation had good antioxidant potential, being able to stimulate glutathione S-transferase (GST) activity and consequently reduce levels of reactive oxygen species (ROS) in lambs that consumed the highest dose of GRF (G-2%). GRF supplementation improved humoral responses, with increased serum levels of heavy-chain and light-chain immunoglobulins; however, there was a reduction in serum ceruloplasmin levels in these lambs. We observed higher concentrations of glucose and triglycerides in lambs in the 2% group. There were lower lymphocyte counts in lambs that received GRF. Lambs supplemented with the highest doses of GRF (G-1% and G-2%) had lower total bacterial counts in the feces. We conclude that the use of GRF in the supplementation of suckling lambs improved animal health, as it stimulated the antioxidant and immune systems and consequently favored their growth.

Moringa stenopetala is often consumed as food and used in folkloric medicine for the management of several diseases. Purpose: This study was set up in order to assess the effect of aqueous extract of Moringa stenopetala on cell viability and oxidative stress biomarkers in BV-2 microglial cells. Aqueous extracts of M. stenopetala were prepared, lyophilized and reconstituted in 0.5% dimethylsulphoxide (DMSO). Cells were treated with M. stenopetala extracts (0.1 - 100 µg/ml) for cell viability and nitric oxide (NO) production tests. However, M. stenopetala extract (50 µg/ml) was used in the treatment of cells for the determination of protein carbonyl content and reactive oxygen species (ROS) level. Incubation of BV-2 microglia cell with M. stenopetala extract maintained cell viability, diminished NO and ROS levels, and reduced protein carbonyl contents Chlorogenic acid, rutin, kaempferol and quercetin derivatives were the main phenolic compounds identified in M. stenopetala leaf extract. These phenolic compounds present in M. stenopetala may be responsible for the mitigation of oxidative stress in BV-2 microglial 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

Background: Curcumin has been used as an additive in the diet of animals in recent years due to the potent medicinal properties of this molecule. Objective: To evaluate whether the addition of curcumin to the diet of calves at different phases (pre- and post-weaning) has a positive effect on metabolic profile, performance, and anti-coccidian action. Methods: Thirtythree Holstein calves were selected at various phases of development: Experiment 1 (E1: n=10) 18±7 (pre-weaning), Experiment 2 (E2: n=11) 64±4 (pre-weaning) and Experiment 3 (E3: n=12) 95±8 (post-weaning) days of life. The calves were separated in three groups according to their phase of development. In each experiment, animals were divided into two sub-groups: control and curcumin. The curcumin groups received 200 mg of additive per animal/day either in milk (pre-weaning) or concentrate (post-weaning). Fecal collections were performed on days 0, 10 and 15 of the experiment to count Eimeria oocysts per gram of feces and to perform fecal score analysis. Complete blood counts, oxidant and antioxidant profiles, protein metabolism markers, lipid levels, glucose levels, and animal weights were measured. Analyses of digestibility and composition of the diet used in Experiment 3 (post-weaning) were also performed. Results: Independent of phase, animals that received curcumin had greater weight gain on days 0 to 15 (E1, E2 and E3 p=0.04, 0.001 and 0.001, respectively), probably due to the increased digestibility of hay and concentrate at 72h (p=0.03 and 0.02, respectively). The supplemented calves had lower level of oxidants (thiobarbituric acid reactive substances –TBARS- and reactive oxygen species –ROS-), indicating that free radical levels in serum and lipid peroxidation were lower. This was probably due to increased enzymatic antioxidants gluthatione S-transferase (E1, E2 and E3 p=0.001, 0.001 and 0.02, respectively), catalase (E1 p=0.001) and superoxide dismutase (E3 p=0.001) in treated animals at day 15. Furthermore, calves receiving curcumin had lower numeric number of Eimeria infection during the experimental period, and the difference was significant in day 15 (E1 and E2 p=0.02, and 0.001, respectively). Conclusion: Curcumin supplementation to dairy calves has coccidiostatic potential, favoring weight gain.Keywords: animal stress; antioxidants; calves; cattle growth; curcumin; Eimeria; parasitology; supplementation. Resumen Antecedentes: Curcumina ha sido utilizada como aditivo en la dieta de animales en los últimos años, debido a las potentes propiedades medicinales de esa molécula. Objetivo: Evaluar si la adición de curcumina en la alimentación de terneras en diferentes fases (pre y post-destete) presenta efecto positivo sobre el perfil metabólico, desempeño de los animales, y acción anti-coccidial. Métodos: Se seleccionaron 33 terneros Holstein en varias etapas de desarrollo: Experimento 1 (E1: n=10) 18±7 (pre-destete), Experimento 2 (E2: n=11) 64±4 (pre-destete) y Experimento 3 (E3: n=12) 95±8 (post-destete) días de vida. Para todos los experimentos, el período experimental fue de 15 días. Los animales se dividieron en dos grupos: control y tratados con curcumina. Los grupos con curcumina recibieron una dosis de 200 mg del aditivo por animal/día en la leche (pre-destete) o en el concentrado (post-destete). Las colectas de heces y sangre fueron realizadas en los días 0, 10 y 15 para conteo de ooquistes de Eimeria por gramo de heces y análisis de puntaje fecal. Se realizó hemograma, perfil oxidante y antioxidante, metabolismo proteico, lipídico, glucosa sanguínea y pesaje de los animales. También se realizó análisis de digestibilidad de la dieta total para los animales del Experimento 3 (post-destete). Resultados: Encontramos que, independientemente de la fase, los animales que recibieron curcumina tuvieron una mayor ganancia de peso en los días 0 a 15 (E1, E2 y E3, p=0,04, 0,001 y 0,001, respectivamente), probablemente debido al aumento de la digestibilidad del heno y concentrado a las 72 h (p=0,03 y 0,02, respectivamente). En los terneros suplementados observamos un nivel más bajo de oxidantes (oxidantes (sustancias reactivas al ácido tiobarbitúrico y especies reactivas de oxígeno); es decir, los niveles séricos de radicales libres y la peroxidación lipídica fueron más bajos. Esto se debió, probablemente, a los antioxidantes enzimáticos glutatión S-transferasa (E1, E2 y E3 p=0,001, 0,001 y 0,02 respectivamente), catalasa (E1, p=0,001) y superóxido dismutasa (E3, p=0,001) que aumentaron en los animales tratados al día 15. Además, los terneros que recibieron curcumina tuvieron niveles más bajos de infección por Eimeria durante el período experimental y fueron significativos en el día 15 (E1 y E2, p=0,02 y 0,001, respectivamente). Conclusión: La suplementación con curcumina tiene potencial coccidiostático y favorece la ganancia de peso en terneros Holstein. Palabras clave: antioxidantes; crecimiento de ganado; curcuminatiene; Eimeria; estrés animal; parasitología; suplementación; terneros. ResumoAntecedentes: Curcumina tem sido usado como aditivo na dieta de animais nos últimos anos, devido as propriedades medicinais potente dessa molécula. Objetivo: Avaliar se a adição de curcumina na alimentação de bezerras em diferentes fases (pré e pós-desmame) apresenta efeito positivo sobre perfil metabólico, desempenho e ação anti-coccidéo. Métodos: Para isso, 33 bezerros holandeses foram selecionados em vários estágios de desenvolvimento: Experimento 1 (E1: n=10) 18±7 (prédesmame), Experimento 2 (E2: n=11) 64±4 (pré-desmame) e Experimento 3 (E3: n=12) 95±8 (pós-desmame) dias de vida. Para todos os experimentos o período experimental foi de 15 dias, assim como foram delineados com dois grupos: controle e tratados com curcumina. Os grupos de curcumina receberam 200 mg do aditivo por animal/dia no leite (pré-desmame) ou em concentrado (pós-desmame). Coletas de fezes e sangue foram realizadas nos dias 0, 10 e 15 de experimento para contagem de oocistos de Eimeria por grama de fezes e análise de escore fecal. Do sangue colhido foram realizados: hemograma, perfil oxidante e antioxidante, metabolismo proteico, lipídico, glicose, além da pesagem dos animais. Também foi realizado análise de digestibilidade da dieta total ofertada aos animais do Experimento 3 (pós-desmame). Resultados: Independentemente da fase, os animais que receberam curcumina tiveram maior ganho de peso do dia 0 a 15 (E1, E2 e E3, p=0,04, 0,001 e 0,001, respectivamente), provavelmente devido ao aumento da digestibilidade ao feno e concentrado após 72 h (p=0,03 e 0,02, respectivamente). Nos bezerros suplementados, observou-se menor nível de oxidantes (substâncias reativas ao ácido tiobarbitúrico e espécies reativas de oxigênio), ou seja, os níveis séricos de radicais livres e a peroxidação lipídica foram menores. Isto foi provavelmente devido a antioxidantes enzimáticos glutationa S-transferase (E1, E2 e E3, p=0,001, 0,001 e 0,02, respectivamente), catalase (E1, p=0,001) e superóxido dismutase (E3, p=0,001) aumentando nestes animais tratados no dia 15. Além disso, bezerros recebendo curcumina tiveram menores níveis de infecção por Eimeria durante o período experimental e significativos no dia 15 (E1 e E2, p=0,02 e 0,001, respectivamente). Conclusão: A suplementação de curcumina aumenta o potencial coccidiostático e favorece o ganho de peso.Palavras-chave: antioxidante; bezerros; crescimento do gado; curcumina; Eimeria; estresse animal; parasitologia; suplementação.

Accumulation of lanthanum oxide nanoparticles (La2O3NPs) in the femur bone of rats after 30 days of oral administration was explored. Also, the influence of La2O3NPs on macro and trace elements in the rats’ femur bone was assessed. Inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma optical spectrometry (ICP OES) were used for total element determination in the bone after decomposition while laser ablation-ICP-MS (LA-ICP-MS) was used to investigate element distribution (bio-imaging) in the bone. Some differences in element concentrations in the bone between the rats treated with La2O3NPs at 1.0 mg kg−1 (T1), 10.0 mg kg−1 (T2), and 100 mg kg−1 (T3) body weight (bw) and the control rats (CTR) were observed. More differences were observed in the bone of rat treated with 10.0 mg kg−1 La2O3NPs bw. However, the highest change observed was for Mg, which concentration ranged from 5230 ± 12 μg kg−1 for the CTR group to 4130 ± 138 μg kg−1 for the T3 group. Minor changes were observed for Ba, Ca, Cr, Cu, Fe, Mg, Na, Pb, Sr, and Zn between CTR and animals treated with La2O3NPs at the different levels of concentration. It was possible to observe from LA-ICP-MS analysis that La2O3NPs were accumulated only on the surface of the bone, not deeper than about 5 μm. LA-ICP-MS allowed also to investigate the distribution of La and the other elements in a cross section of the femur bone head, where higher amounts of the elements are present at the external part of the bone. Therefore, it was demonstrated that La2O3NPs are incorporated on the surface of the bone and it has a small influence on some of the other elements evaluated.

The aim of this study was to investigate the ability of tannic acid (TA) in preventing memory deficits and neurochemical alterations observed in a model for Sporadic Dementia of Alzheimer’s Type. R...

In hypertensive individuals, platelet morphology and function have been discovered to be altered, and this has been linked to the development of vascular disease, including erectile dysfunction (ED). The impact of nutritional supplementation with Cyperus esculentus (tiger nut, TN) and Tetracarpidium conophorum (walnut, WN) on androgen levels, ectonucleotidases, and adenosine deaminase (ADA) activities in platelets from L-NAME (Nω-nitro-L-arginine methyl ester hydrochloride) challenged rats were investigated. We hypothesized that these nuts may show a protective effect on platelets aggregation and possibly enhance the sex hormones, thereby reverting vasoconstriction. Wistar rats (male, 250–300 g, n = 10) were grouped into seven groups as follows: basal diet control group (I), basal diet/L-NAME/Viagra (5 mg/kg/day) as positive control group (II), ED-induced group (basal diet/L-NAME) (III), diet supplemented processed TN (20%)/L-NAME (IV), diet supplemented raw TN (20%)/L-NAME (V), diet supplemented processed WN (20%)/L-NAME (VI), and diet supplemented raw WN (20%)/L-NAME (VII). The rats were given their regular diet for 2 weeks prior to actually receiving L-NAME (40 mg/kg/day) for ten days to induce hypertension. Platelet androgen levels, ectonucleotidases, and ADA were all measured. L-NAME considerably lowers testosterone levels (54.5 ± 2.2, p &lt, 0.05). Supplementing the TN and WN diets revealed improved testosterone levels as compared to the control (306.7 ± 5.7), but luteinizing hormone levels remained unchanged. Compared to control groups, the L-NAME-treated group showed a rise in ATP (127.5%) hydrolysis and ADA (116.7%) activity, and also a decrease in ADP (76%) and AMP (45%) hydrolysis. Both TN and WN supplemented diets resulted in substantial (p &lt, 0.05) reversal effects. Enhanced testosterone levels and modulation of the purinergic system in platelets by TN and WN could be one of the mechanisms by which they aid in vasoconstriction control.

This study aimed to produce dog food containing natural antioxidants (blend of essential oils and vitamin E) to replace synthetic antioxidants and determine the effects on food conservation and animal health sequentially. The foods were produced in a commercial factory, and the antioxidants were added at the oil bath stage. Ten adult beagle dogs were used, divided into two treatments; control treatment (CON; synthetic antioxidant feed [butylhydroxytoluene]) and test treatment (NAT; natural antioxidant feed; blend of essential oils from clove, rosemary, oregano, and vitamin E). The dogs were weighed at the beginning and end of each experimental period, and there were no treatment effects for body weight. In both treatments, food conservation efficiency was observed, demonstrating the feasibility of using natural sources as antioxidants in dog food because chemical and oxidative variables did not differ regardless of the antioxidant used during production. The animals’ metabolic and haematological variables were not influenced by the treatments; however, a reduction in the number of lymphocytes was observed over time only in the dogs of the NAT group. There was also a day effect for total leukocyte, neutrophil and erythrocyte counts only in NAT animals, which means a significant increase (p ≤ 0.05) in the variables on d 28. There was an effect of the treatment and an interaction treatment x day for the total bacterial count, whereas a decrease in the bacterial count (p p ≤ 0.05) to minimise oxidative stress. In group NAT, the NPSH and glutathione S-transferase levels were increased, which may explain the decrease in ROS levels. It was concluded that natural antioxidants in dog feed, in addition to promoting feed conservation, stimulate levels of systemic antioxidants and minimise the impacts caused by free radicals in the dogs’ blood.

The present study aimed to determine whether the inclusion of a mixture based on Saccharomyces cerevisiae lysate, zeolite, silicon dioxide, propylene glycol, Carduus marianus extract, soy lecithin, and carbonate in the piglet diet would be able to minimize the negative effects caused by feed with aflatoxin; a study focusing on animal health and performance. Seventy-two entire male piglets (7.35 ± 1.17 kg) weaned with an average of 26 days were used, allotted into four groups, with six repetitions (pens) per group and three piglets/pen. The treatments were as follows: NoAfla-NoAntiMyc - negative control (without aflatoxin); Afla-NoAntiMyc - positive control (500 ppb of aflatoxin); NoAfla-AntiMyc - 1000 mg/kg of anti-mycotoxin mixture; Afla-AntiMyc - 500 ppb aflatoxin + 1000 mg/kg anti-mycotoxin. We evaluated the performance (feed intake - FI, weight gain - WG and feed:gain ratio- FGR) andblood variables (10 days between samples). On day 32, six pigs from each group (a total of 24 pigs) were slaughtered to collect fragments of the liver, intestine, and spleen for analysis of oxidants/antioxidants and histology. It was observed that piglets in the positive control group (Afla-NoAntiMyc) had lower body weight and weight gain when compared to the other groups during the experimental period. Also, piglets from Afla-NoAntiMyc consumed less feed between days 1 to 20 and 1 to 30 compared to NoAfla-NoAntiMyc. A considerable increase in liver enzymes aspartate aminotransferase and alanine aminotransferase in the piglets' serum of Afla-NoAntiMyc compared to other treatments, which indicates that the anti-aflatoxin blend worked. Fewer neutrophils and an increase in monocyte were observed in the piglets of Afla-NoAntiMyc compared to NoAfla-NoAntiMyc; changes that were not seen in the animals of Afla-AntiMyc. We did not see any change in the oxidant and antioxidant status in the piglet serum during the experimental period; different from what happened in Afla-NoAntiMyc piglets in the liver (higher glutathione reductase activity and levels of reactive oxygen species - ROS), in the spleen (higher levels of ROS) and the intestine/jejunum (reduction of nitrate/nitrite levels - NOx). Intestinal morphometry revealed that piglets from Afla-NoAntiMyc had higher villus height than the other groups, while the folded size was smaller in this group. The crypt depth was greater in the intestine of piglets in both treatments that consumed aflatoxin. In general, it is concluded that the consumption of aflatoxin B1 by piglets has negative impacts on the health and, consequently, the animals' performance; however, supplementation of the contaminated feed with an anti-mycotoxin blend was able to protect the piglets, minimizing the negative problems caused by the mycotoxin.

The objective of this work was to determine whether preventive consumption of a homeopathic product via drinking water would protect mouse kidneys from a challenge with the nephrotoxic antibiotic gentamicin. We used 40 Swiss mice divided into four groups with ten animals each. The homeopathic product was supplied through water for 30 days in a preventive manner and gentamicin for 10 days to induce an experimental renal failure. The groups were as follows: Negative-CT (homeopathic and gentamicin was not provided), Positive-CT (did not receive homeopathic, but received gentamicin 40 mg/kg), T2 (received 0.002 ml of the product per animal/day, and received gentamicin 40 mg/kg), and T4 (0.004 ml of the product per animal/day and received gentamicin 40 mg/kg). On days 12 and 20, blood and tissue samples were collected from five animals in each group. No histopathological lesions were found in mouse kidneys. However, levels of thiobarbituric acid reactive substances, reactive oxygen species, and nitrite/nitrate ratios in the kidney of the Positive-CT group were higher compared to the other groups. As for glutathione S-transferase, on the 20th day, the groups that used the homeopathic product (T2 and T4) had higher activities than the positive TC. Therefore, the results suggest that prophylactic consumption of the hepatoprotective homeopathic product can decrease lipid peroxidation, nitrous stress, and oxidative stress at the renal level when consecutive doses of gentamicin induce insufficiency. El objetivo de este trabajo fue determinar si el consumo preventivo de un producto homeopático a través del agua potable protegería los riñones de los ratones de un desafío con el antibiótico nefrotóxico gentamicina. Usamos 40 ratones suizos divididos en cuatro grupos con diez animales cada uno. El producto homeopático se suministró a través de agua durante 30 días de forma preventiva y gentamicina durante 10 días para inducir una insuficiencia renal experimental. Los grupos fueron los siguientes: CT negativo (no se proporcionó homeopático y gentamicina), CT positivo (no recibió homeopático, pero recibió gentamicina 40 mg/kg), T2 (recibió 0,002 ml del producto por animal/día, y recibió gentamicina 40 mg/kg) y T4 (0,004 ml del producto por animal / día y recibió gentamicina 40 mg/kg). Los días 12 y 20, se recogieron muestras de sangre y tejido de cinco animales de cada grupo. No se encontraron lesiones histopatológicas en riñones de ratón. Sin embargo, los niveles de sustancias reactivas con ácido tiobarbitúrico, especies reactivas de oxígeno y relaciones nitrito/nitrato en el riñón del grupo de CT positiva fueron más altos en comparación con los otros grupos. En cuanto a la glutatión S-transferasa, el día 20, los grupos que utilizaron el producto homeopático (T2 y T4) tuvieron actividades más altas que los TC positivos. Por lo tanto, los resultados sugieren que el consumo profiláctico del producto homeopático hepatoprotector puede disminuir la peroxidación lipídica, el estrés nitroso y el estrés oxidativo a nivel renal cuando dosis consecutivas de gentamicina inducen insuficiencia. O objetivo deste trabalho foi determinar se o consumo preventivo de um produto homeopático via água potável protegeria os rins de camundongos de um desafio com o antibiótico nefrotóxico gentamicina. Foram utilizados 40 camundongos Swiss divididos em quatro grupos com dez animais cada. O produto homeopático foi fornecido por meio de água por 30 dias de forma preventiva e gentamicina por 10 dias para induzir insuficiência renal experimental. Os grupos foram os seguintes: TC-negativa (não foi fornecida gentamicina e homeopática), TC-positiva (não recebeu homeopatia, mas recebeu gentamicina 40 mg/kg), T2 (recebeu 0,002 ml do produto por animal/dia, e receberam gentamicina 40 mg/kg) e T4 (0,004 ml do produto por animal/dia e receberam gentamicina 40 mg/kg). Nos dias 12 e 20, amostras de sangue e tecido foram coletadas de cinco animais em cada grupo. Nenhuma lesão histopatológica foi encontrada em rins de camundongos. No entanto, os níveis de substâncias reativas ao ácido tiobarbitúrico, espécies reativas de oxigênio e relações nitrito/nitrato no rim do grupo CT-positivo foram maiores em comparação com os outros grupos. Já para a glutationa S-transferase, no 20º dia, os grupos que usaram o produto homeopático (T2 e T4) apresentaram atividades superiores ao TC positivo. Portanto, os resultados sugerem que o consumo profilático do produto homeopático hepatoprotetor pode diminuir a peroxidação lipídica, o estresse nitroso e o estresse oxidativo no nível renal quando doses consecutivas de gentamicina induzem insuficiência.

This study examined the behavioral responses, purinergic receptor densities, ectonucleotidases (E-NTPDase), adenosine deaminase (ADA) activity, and nitric oxide (NO) levels along with the parameters of oxidative stress-related to erectile function in the cerebral cortex (CC) of L-NAME-challenged rats pretreated with tigernut (TN) and walnut (WN) dietary supplementation. Wistar rats (male) of 70 total animals (250-300 g) were used in this research and hence separated into seven groups (n = 10): Group I: normal control-fed basal diet; Group II: positive control-fed basal diet/L-NAME/Sildenafil citrate (5 mg kg-1 day-1 ); Group III: ED-induced (placed on a basal diet/L-NAME); Group IV: diet supplemented with processed TN (20%)/L-NAME; Group V: diet supplemented with raw TN (20%)/L-NAME; Group VI: diet supplemented with processed WN (20%)/L-NAME; and Group VII placed on a diet supplemented with raw WN (20%)/L-NAME. The rats were pretreated for 2 weeks before the L-NAME (40 mg kg-1 day-1 ) challenge on their respective diet. L-NAME brought about a decrease in the sexual behaviors evaluated while the effect was significantly reversed by supplemented diets containing TN and WN. L-NAME increased the levels of reactive oxygen species and malondialdehyde, E-NTPDase as well as ADA activities, and caused the level of NO in the CC as well as the purinoreceptor densities to be downregulated. Treatments with enriched diets, however, greatly reverse these effects. The behavioral responses and neuromodulatory capacity of the nuts displayed on the CC can, therefore, further support their aphrodisiac property. PRACTICAL APPLICATIONS: The results revealed the ability of tigernut (TN; Cyperus esculentus L.) and walnut (WN; Tetracarpidium conophorum Mull. Arg.) to enhance behavioral responses; modulate purinergic receptor densities, E-NTPDase, and ADA activities; increase NO levels; and prevent oxidative stress related to erectile function in the CC of L-NAME-challenged Wistar rats. The results show that these nuts are useful feeds for both animal and human nutrition.

Graphical abstract, Highlights • The coexistence of diabetes and hypertension represents a major risk factor for the onset of cardiovascular problems. • The purinergic signaling pathway constitutes a ubiquitous system of cell–cell communication. • Purinergic system plays a pivotal role in physiopathological conditions. • Several alterations in purine metabolism have been demonstrated in diabetes and hypertension. • Purinergic system can be an important target related to therapeutic approaches in diabetes and hypertension., Diabetes mellitus (DM) and hypertension are highly prevalent worldwide health problems and frequently associated with severe clinical complications, such as diabetic cardiomyopathy, nephropathy, retinopathy, neuropathy, stroke, and cardiac arrhythmia, among others. Despite all existing research results and reasonable speculations, knowledge about the role of purinergic system in individuals with DM and hypertension remains restricted. Purinergic signaling accounts for a complex network of receptors and extracellular enzymes responsible for the recognition and degradation of extracellular nucleotides and adenosine. The main components of this system that will be presented in this review are: P1 and P2 receptors and the enzymatic cascade composed by CD39 (NTPDase; with ATP and ADP as a substrate), CD73 (5′-nucleotidase; with AMP as a substrate), and adenosine deaminase (ADA; with adenosine as a substrate). The purinergic system has recently emerged as a central player in several physiopathological conditions, particularly those linked to inflammatory responses such as diabetes and hypertension. Therefore, the present review focuses on changes in both purinergic P1 and P2 receptor expression as well as the activities of CD39, CD73, and ADA in diabetes and hypertension conditions. It can be postulated that the manipulation of the purinergic axis at different levels can prevent or exacerbate the insurgency and evolution of diabetes and hypertension working as a compensatory mechanism.

Aluminum (Al) is a neurotoxin and is associated with the etiology of neurodegenerative diseases, such as Alzheimer’s disease (AD). The Al-free ion (Al3+) is the biologically reactive and toxic form. However, the underlying mechanisms of Al toxicity in the brain remain unclear. Here, we evaluated the effects of Al3+ (in the chloride form—AlCl3) at different concentrations (0.1–100 µM) on the morphology, proliferation, apoptosis, migration and differentiation of neural progenitor cells (NPCs) isolated from embryonic telencephalons, cultured as neurospheres. Our results reveal that Al3+ at 100 µM reduced the number and diameter of neurospheres. Cell cycle analysis showed that Al3+ had a decisive function in proliferation inhibition of NPCs during neural differentiation and induced apoptosis on neurospheres. In addition, 1 µM Al3+ resulted in deleterious effects on neural phenotype determination. Flow cytometry and immunocytochemistry analysis showed that Al3+ promoted a decrease in immature neuronal marker β3-tubulin expression and an increase in co-expression of the NPC marker nestin and glial fibrillary acidic protein. Thus, our findings indicate that Al3+ caused cellular damage and reduced proliferation and migration, resulting in global inhibition of NPC differentiation and neurogenesis.

The role of cholinesterase in inflammatory reactions has been described in several infectious diseases. However, in Brucella spp. this has not yet been studied. Therefore, the objective of this study was to evaluate whether experimental infection by Brucella ovis alters the cholinergic activity in pro- or anti-inflammatory responses to the disease. For the study 48 mice were used, 24 infected by B. ovis and 24 non-infected. We collected samples of whole blood on days 7, 15, 30 and 60 post-infection (PI) by B. ovis. Acetylcholinesterase (AChE) activity in the blood increased on days 15 and 60 PI (P 0.05). Butyrylcholinesterase (BChE) activity in serum increased on days 7 and 60 PI (P 0.05). An increase in serum free radical levels occurred on days 7, 15 and 60 PI (P 0.05), and consequently superoxide dismutase activity increased on day 15 PI (P 0.05). A reduction in catalase activity occurred when the infection became chronic (60 PI). The increase in AChE and BChE characterized a pro-inflammatory response, since these enzymes regulate levels of acetylcholine (ACh) and butyrylcholine (BuSCh), molecules with anti-inflammatory properties. Therefore, with the increase of cholinesterase activity, there was an extracellular reduction of ACh, an inhibitor of several inflammatory mediators. This proinflammatory response of B. ovis infection leads to oxidative stress, and consequently to cellular damage.

Melanoma is a type of skin cancer originated by the malignant transformation of melanocytes. Increasing incidence and mortality require efforts focused on studies and research about this cancer. Its microenvironment is rich in extracellular ATP, but there are no studies evaluating the ectonucleotidases and ATP effects on tumor-derived melanoma cells with known amounts of ATP. This way, the objective of this work was to evaluate the purinergic signaling in the pathophysiology of in vivo melanoma and the in vitro effects of ATP signaling. We found increased and effective extracellular ATP hydrolysis in platelets and a significant decrease of extracellular ATP levels and adenosine hydrolysis. In addition, we cultured PBMCs of melanoma patients and used ATP salt with specific concentrations to evaluate its signaling effects. The enzymatic activity analysis revealed that even with higher ATP doses cells metabolize adenine nucleotides less efficiently, and present low ATP, ADP and AMP hydrolytic activity in CM compared to CT cells. In summary, we showed for the first time important data about the purinergic signaling in the pathophysiology of melanoma and ATP signaling exercising immunosuppressive effects. Therefore, as already shown for other tumors, the purinergic signaling should be considered a potential target for melanoma management and treatment and could offer novel therapeutic prospects.

Systemic lupus erythematosus (SLE) is an autoimmune and inflammatory disease with periods of exacerbation and remission. SLE is characterized by the irreversible breakdown of immunological self-tolerance, where there is deregulation of multiple aspects of the immune system. SLE immune dysfunction is characterized by activation of autoreactive T lymphocytes, and hyperactivity of B lymphocytes with consequent production of several autoantibodies. ATP is a purinergic mediator released into the extracellular space in response to cell and tissue damage which operates as a danger signal to modulate immune and inflammatory responses. ATP binds to P2 receptors and its levels are regulated by NTPDase (CD39). SLE patients exhibit increased levels of ATP which binds to P2X receptors resulting in activation of the inflammasome and consequent release of IL-1β and IL-18, cytokines associated with disease pathogenesis. CD39 is upregulated in SLE representing an important immunoregulatory mechanism by controlling inflammation and favoring the production of adenosine. The aim of this review is to clarify the effects of ATP on the modulation of the inflammatory process and immune responses via P2 receptors as well as the role of NTPDase in the immunopathogenesis of SLE.

Objective Investigate Vitamin D3 (VD3) effect on the Acetylcholinesterase (AChE), oxidative damage and behavioral tests in animals subjected to Intracerebroventicular injection of Streptozotocin (ICV-STZ) simulating a Sporadic Dementia of Alzheimer's Type (SDAT) and treated with VD3 (21 days). Methods Animals were divided into eight groups: Vehicle, VD12.5 μg/kg, VD42 μg/kg, VD125 μg/kg, STZ, STZ+VD12.5 μg/kg, STZ+VD42 μg/kg, STZ+VD125 μg/kg. Results VD3 prevented the increase in AChE in groups of VD42 µg/kg and VD125 µg/kg; in AChE of synaptossomes and TBARS levels prevented the increase in group VD125 µg/kg; in ROS levels there was not a significant difference; for the Carbonyl Content all doses prevented the increase. Total Thiols prevent the decrease in VD42 µg/kg and VD125 µg/kg, and Reduced Glutathione prevented the decrease in VD125 µg/kg, Oxidized Glutathione prevented the increase in VD125 µg/kg. In relation to behavioral tests, the VD3 prevented the increase in time to find (days 2 and 3), in the time to find the platform (day 3) and in time spent in the quadrant (day 2). However, in relation to crossings there was not difference in groups. These results indicated the therapeutic effect of the VD3 in model of STZ in rats.

The aim of this study was to evaluate the metaphylactic effect of minerals on immunological and antioxidant responses, as well as performance and prevention of coccidiosis in newborn lambs. We divided 110 newborn lambs into two groups (55/group): control (untreated) and treated with two doses of 0.33 mL/kg of a mineral complex (zinc, copper, selenium, and manganese) on day of life (DOL) 1 and 30. Total blood was collected at DOL 1, 15, 30 and 45 to measure antioxidant enzymes, biochemical and immunology analyses, and haemogram. Treated animals were heavier (P .05) than untreated lambs on DOL 15 and 45, but not on DOL 30 due to a coccidiosis outbreak. Catalase activity did not differ between groups, while superoxide dismutase and xanthine oxidase activities were higher (P .05) in treated lambs compared with control animals. Serum levels of total protein and globulins were higher (P .05) in treated animals (DOL 15, 30 and 45). A significant increased on the number of lymphocytes (DOL 45), as well as on seric levels of immunoglobulins (IgM and IgG) was observed in treated animals (DOL 15 and 30). Serum Ig levels remained constant throughout the experiment in the treated group, but fluctuated in the control group. Serum glucose levels were greater in treated animals (DOL 15 and 30). It is possible to conclude that subcutaneous administration of minerals has beneficial effects on lambs by increasing antioxidant and immunological defenses, reflected by greater weight gain, which could mitigate the impact of coccidiosis.

The objective of this study was to evaluate whether the addition of curcumin to the diet of lactating ewes had positive effects on animal health, productive performance and milk quality. Eighteen Lacaune females were divided into two groups: control (group C) and treated (group T). Animals of group T received a diet supplemented with curcumin at 100 mg/kg feed for 15 d. On days 0, 10 and 15, samples of blood and milk were collected. The number of total blood leukocytes was lower on days 10 and 15, as a consequence of the reduction in the number of neutrophils and lymphocytes in group T (P

Several evidences have suggested the involvement of enzymes belonging to the phosphotransfer network, formed by creatine kinase (CK), pyruvate kinase (PK) and adenylate kinase (AK), as well the oxidative stress on the pathogenesis of infectious diseases associated with the central nervous system (CNS). Thus, the aim of this study was to evaluate whether listeriosis alters the brain energy metabolism and/or causes oxidative stress in different brain structures of cattle experimentally infected by Listeria monocytogenes. The cytosolic CK activity was inhibited in the cerebral cortex, cerebellum, brainstem and hippocampus of infected animals compared to uninfected animals, while the mitochondrial CK activity was increased. The PK activity was inhibited in all brain structures of infected animals, while the AK activity was unchanged. Na+, K+-ATPase activity decreased in the cerebral cortex, cerebellum and hippocampus of animals infected by L. monocytogenes. Regarding the oxidative strees variables, the cerebellum and brainstem of infected animals showed increased thiobarbituric acid reactive substances, while the catalase activity was inhibited. Glutathione S-transferarase was inhibited in the cerebral cortex and brainstem of infected animals, and it was increased in the cerebellum. L. monocytogenes was quantified in the liver (n = 5/5) and cerebral cortex (n = 4/5) of the infected cattle. Based on these evidences, the nucleocytoplasmic communication between CK isoenzymes was insufficient to avoid an impairment of cerebral bioenergetics. Moreover, the inhibition on brain PK activity caused an impairment in the communication between sites of ATP generation and ATP utilization. The lipid peroxidation and alteration on antioxidant status observed in some brain structures were also involved during the disease. In summary, these alterations contribute to disease pathogenesis linked to CNS during cattle listeriosis.

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. The present study investigated the effects of 50 and 100 mg/kg berberine (BRB) on recognition memory, oxidative stress, and purinergic neurotransmission, in a model of sporadic dementia of the Alzheimer's type induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) in rats. Rats were submitted to ICV-STZ 3 mg/kg or saline, and 3 days later, were started on a treatment of BRB or saline for 21 days. The results demonstrated that BRB was effective in protecting against memory impairment, increased reactive oxygen species, and the subsequent increase in protein and lipid oxidation in the cerebral cortex and hippocampus, as well as δ-aminolevulinate dehydratase inhibition in the cerebral cortex. Moreover, the decrease in total thiols, and the reduced glutathione and glutathione S-transferase activity in the cerebral cortex and hippocampus of ICV-STZ rats, was prevented by BRB treatment. Besides an antioxidant effect, BRB treatment was capable of preventing decreases in ecto-nucleoside triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase (EC-5'-Nt), and adenosine deaminase (ADA) activities in synaptosomes of the cerebral cortex and hippocampus. Thus, our data suggest that BRB exerts a neuroprotective effect on recognition memory, as well as on oxidative stress and oxidative stress-related damage, such as dysfunction of the purinergic system. This suggests that BRB may act as a promising multipotent agent for the treatment of AD.

Aluminum (Al) is ubiquitously present in the environment and known to be a neurotoxin for humans. The trivalent free Al anion (Al3+) can cross the blood-brain barrier (BBB), accumulate in the brain, and elicit harmful effects to the central nervous system (CNS) cells. Thus, evidence has suggested that Al increases the risk of developing neurodegenerative diseases, particularly Alzheimer’s disease (AD). Purinergic signaling has been shown to play a role in several neurological conditions as it can modulate the functioning of several cell types, such as microglial cells, the main resident immune cells of the CNS. However, Al effects on microglial cells and the role of the purinergic system remain elusive. Based on this background, this study is aimed at assessing the modulation of Al on purinergic system parameters of microglial cells. An in vitro study was performed using brain microglial cells exposed to Al chloride (AlCl3) and lipopolysaccharide (LPS) for 96 h. The uptake of Al, metabolism of nucleotides (ATP, ADP, and AMP) and nucleoside (adenosine), and the gene expression and protein density of purinoceptors were investigated. The results showed that both Al and LPS increased the breakdown of adenosine, whereas they decreased nucleotide hydrolysis. Furthermore, the findings revealed that both Al and LPS triggered an increase in gene expression and protein density of P2X7R and A2AR receptors, whereas reduced the A1R receptor expression and density. Taken together, the results showed that Al and LPS altered the setup of the purinergic system of microglial cells. Thus, this study provides new insights into the involvement of the purinergic system in the mechanisms underlying Al toxicity in microglial cells.

Cadmium has several toxic effects to human health, including carcinogenicity, nephrotoxicity, hepatotoxicity, cardiovascular, reproductive toxicities, neurotoxicity, among others. This chapter will focus mainly on cadmium toxicity: from its analytical aspects to neuronal impairment. In this context, the knowledge of analytical methods to quantify cadmium is extremely needed. The normal range of cadmium in different biological samples, and the treatment that is necessary to measure cadmium on them will be presented. In addition, the literature data about cadmium neurotoxicity bringing parameters of the cholinergic system, purinergic system, Na+,K+-ATPase activity, oxidative stress, neurotransmitter imbalance and histological brain changes will be discussed. Cd acts as a neurotoxin; a scientific fact. However, the findings underline the need for further research in the field of Cd-induced neurotoxicity, as a deeper understanding of the mechanisms underlying the neurobehavioral impairment could shed more light on the causes of its well-established cognitive implications. It is necessary to look at gender and age differences in Cd susceptibility and the role of epigenetics in determining long-term and late-onset health effects from Cd. Finally, measures should be taken to reduce Cd exposure in the general population in order to minimize the risk of health damage.

The objective of this study was to determine whether a phytogenic blend (PB), formulated based on organic acids, tannins, curcumin, and essential oils, could replace the antimicrobials commonly used as growth promoters in the poultry industry without compromising zootechnical performance, health, or meat quality. In addition, our goal was to report the anti-aflatoxin effect of this phytogenic blend. Four treatments were used: TC, or control; T250, T500, and T1000, representing test doses of 250, 500, 1000 mg PB/kg of feed, respectively, or a 34-day experiment (initial and growth phases). On day 22 of the study and age of the birds, 500 ppb of aflatoxin was included in the diet to represent an intestinal challenge and to evaluate the growth-promoting effects of PB. In the initial phase (up to 21 days), there were no differences between groups in weight gain, feed intake, or feed conversion. After adding an aflatoxin-contaminated feed, doses of 250 and 500 mg/kg minimized the adverse effects on feed consumption and feed conversion caused by aflatoxin; but 1000 mg/kg did not differ between groups. In birds that consumed PB (T250, T500, and T1000) compared to the control, there were the following changes: 1) lower counts of heterophiles, lymphocytes, and monocytes; 2) lower lipid peroxidation and high non-protein thiols levels in breast meat; 3) lower bacteria counts in broiler litter; and 4) lower ALT levels. Greater intestinal villus/crypt ratios were observed at T250 and T500. The dose of 250 mg/kg reduced saturated fatty acids and increased unsaturated fatty acids. The chemical-physical composition of the meat did not differ between treatments. The findings suggest that the addition of a PB has a high potential to improve performance for chickens in the growing stage and minimize the adverse effects of aflatoxicosis.

Introduction Metabolic syndrome (MetS) is a disorder that is closely associated with risk factors that increase the chance of atherosclerosis and cardiovascular diseases. We demonstrate the presence of inflammation and oxidative stress in patients with MetS through levels of antioxidants and oxidative and inflammatory markers, in order to determine influential variables in therapy. Methods: In this study, lipid peroxidation, carbonylated protein content and enzymatic and non-enzymatic antioxidants were evaluated in samples obtained from 30 patients with MetS and 30 control patients. In addition, acetylcholinesterase (AChE) activity, C-reactive protein (CRP) and uric acid (UA) levels were determined to investigate the inflammatory process in patients with MetS. Results: Our results demonstrated an increase in the levels of oxidative markers, such as substances reactive to thiobarbituric acid (TBARS) and carbonyl protein. In addition, a decrease in the defense of non-enzymatic antioxidants, such as levels of vitamin C and glutathione (GSH) in patients with MetS. As for inflammatory markers, CRP and UA were increased in patients with MetS. Finally, activation of the cholinergic anti-inflammatory pathway was observed due to decreased AchE activity in patients with MetS. Conclusion The analyzes indicated oxidative stress, together with a reduction in the levels of antioxidant enzymes, corroborating the high consumption of these proteins. In addition, inflammation and activation of the cholinergic anti-inflammatory pathway was observed by the AChE analysis. Thus, the activation of this pathway can be studied as a possible route to a potential therapy. In addition, the markers AChE, CRP and UA may be used as a focus for the treatment of MetS.

Glycerol monolaurate (GML) is composed of lauric acid and glycerol. Research has shown that such organic acids can minimize negative effects caused by mycotoxins. Therefore, the objective of this study was to determine whether adding GML (free or encapsulated) to chick feed minimizes the effects of natural contamination by fumonisin (Fusarium verticillioides), evaluating parameters such as biochemistry, antioxidant properties, histological analysis and chick growth. Were weighed 84 chicks of the Cobb 500 strain and randomly distributed them into six groups of two replicates each (n = 14). The F group consumed feed containing fumonisin (levels 400 ppb), with no performance enhancer; F + ZB- feed with fumonisin (levels 400 ppb) + zinc bacitracin; F + GLM100 - feed with fumonisin (levels 400 ppb) + 100 mg of GML/kg of feed; F + NGLM4 - feed with fumonisin (levels 400 ppb) + 4 mg GML/kg in nanocapsules added to the feed; F + NGLM8 - fumonisin feed (levels 400 ppb) + 8 mg GML/kg in nanocapsules in the feed; and F0 - fumonisin-free feed (negative control) + zinc bacitracin. The body weights of birds fed with feed fumonisin-contaminated feed (F, F + ZB, F + GLM100, F + NGLM4 and F + NGLM8) were significantly lower (P 0.05) than those of the negative control (F0), despite the use of GML (free and nanoencapsulated). Serum levels of triglycerides, globulins and cholesterol were significantly lower in the F0 group than in the other groups (P 0.05), except for the F + NGLM8 group. Significantly greater levels of lipid peroxidation were observed in livers in the groups that consumed fumonisin than in the control group (F0) (P 0.05). Serum levels of reactive oxygen species were significantly lower in groups F + NGLM8 and F0 than in the other treatments (P 0.05). Superoxide dismutase activity was significantly greater in groups F + NGLM8 and F0 than in groups F, F + ZB and F + NGLM4. Hepatic catalase activity was significantly lower in birds that consumed contaminated feed (F, F + ZB, F + GLM100, F + NGLM4 and F + NGLM8) than in the control group (F0). Greater hepatic glutathione S-transferase activity was observed in the F + NGLM8 group than in the F0 group. Despite changes in cellular lesions in the liver, no histological changes were observed in the liver or intestines, even though visually there was yellowing of the liver. Taken together, the data suggest that free or nano-encapsulated GML did not minimize oxidative stress caused by fumonisin, and consequently, these birds had less weight gain.

The central nervous system of the intermediate host plays a central role in lifelong persistence of Toxoplasma gondii as well as the pathogenesis of congenital toxoplasmosis and reactivated infection in immunocompromised individuals. The purinergic system has been implicated in a wide range of immunological pathways for controlling intracellular responses to pathogens, including T. gondii. In the present study, we investigated the effect of resveratrol (RSV) on ectonucleotidases, adenosine deaminase (ADA), and purinergic receptors during chronic infection by T. gondii. For this study, Swiss mice were divided into control (CTL), resveratrol (RSV), infected (INF), and INF+RSV groups. The animals were orally infected with the VEG strain and treated with RSV (100 mg/kg, orally). Ectonucleotidase activities, P2X7, P2Y1, A1, and A2A purinergic receptor density, ROS, and thiobarbituric acid reactive substances levels were measured in the cerebral cortex of mice. T. gondii infection increased NTPDase and reduced ADA activities. Treatment with RSV also affected enzymes hydrolysing extracellular nucleotides and nucleosides. Finally, RSV affected P1 and P2 purinergic receptor expression during T. gondii infection. Overall, RSV-mediated beneficial changes in purinergic signalling and oxidative stress, possibly improving cerebral cortex homeostasis in T. gondii infection.

The objective of this study was to evaluate whether experimental infection with Listeria monocytogenes alters the activity of triphosphate diphosphohydrolase (NTPDase), 5′-nucleotidase, and adenosine deaminase (ADA) in cattle. Ten male Holstein breed cattle were divided in two groups of five animals each: a control group, and a group infected with a pathogenic strain of L. monocytogenes. We drew blood for platelets on days 0, 7 and 14 of the experiment. On the 14th day post infection (PI), the animals were euthanized. Brain, spleen and liver were processed for histopathological examination and measurement of enzyme activities. The five (n = 5/5) bovines experimentally infected by L. monocytogene were positive-PCR in hepatic tissue. In the brain, only four (n = 4/5) of these animals were positive-PCR for listeriosis. There were no differences in platelet counts between groups (P > 0.05). In platelets, NTPDase activity (with ATP and ADP as substrates) were higher on the 7th PI day in the infected group, whereas the activities of 5′-nucleotidase and ADA were higher on the 7th and 14th PI. In serum and liver, ADA activity was higher in infected animals, but was lower on day 14 PI in spleen. NTPDase activity (with ATP as substrate) was higher in the cerebellum of infected animals, but was lower in the cerebral cortex and medulla oblongata. NTPDase activity (with ADP as substrate) was lower in the cerebellum and cerebral cortex of infected animals, whereas 5′-nucleotidase was higher. ADA activity was lower in the cerebellum, cerebral cortex and medulla oblongata in infected animals compared with controls. In conclusion, there appears to be a protective immunomodulatory response in spleen and brain structures of cattle infected with L. monocytogenes.

The objective of this study was to evaluate the activity of adenosine deaminase (ADA) and its participation in the modulation of the inflammatory responses of mice experimentally infected with B. ovis. We used 48 animals, divided in two groups: group A (control) and group B (infected). We evaluated ADA activity and C-reactive protein (CRP) concentrations at four time points (days 7, 15, 30, and 60) post-infection (PI). There was a reduction in ADA activity in the acute phase (day 15 PI), followed by elevation when the infection became chronic (days 30 and 60 PI). Serum C-reactive protein levels were higher in infected animals than in the control group at all time points post-infection (P

Quercetin is reported to exert a plethora of health benefits through many different mechanisms of action. This versatility and presence in the human diet has attracted the attention of the scientific community, resulting in a huge output of in vitro and in vivo (preclinical) studies. Therefore, we hypothesized that quercetin can protect Na+,K+-ATPase activity in the central nervous system, reestablish the peripheral cholinesterases activities, and reduce oxidative stress during demyelination events in rats. In line with this expectation, our study aims to find out how quercetin acts on the Na+,K+-ATPase activity in the central nervous system, peripheral cholinesterases, and stress oxidative markers in an experimental model of demyelinating disease. Wistar rats were divided into 4 groups: vehicle, quercetin, ethidium bromide (EB), and EB plus quercetin groups. The animals were treated once a day with vehicle (ethanol 20%) or quercetin 50 mg/kg for 7 (demyelination phase, by gavage) or 21 days (remyelination phase) after EB (0.1%, 10 μL) injection (intrapontine).The encephalon was removed, and the pons, hypothalamus, cerebral cortex, hippocampus, striatum, and cerebellum were dissected to verify the Na+,K+-ATPase activity. Our results showed that quercetin protected against reduction in Na+,K+-ATPase in the pons and cerebellum in the demyelination phase, and it increased the activity of this enzyme in the remyelination phase. During the demyelination, quercetin promoted the increase in acetylcholinesterase activity in whole blood and lymphocytes induced by EB, and it reduced the increase in acetylcholinesterase activity in lymphocytes in the remyelination phase. On day 7, EB increased the superoxide dismutase and decreased catalase activities, as well as increased the thiobarbituric acid–reactive substance levels. Taken together, these results indicated that quercetin regulates the Na+,K+-ATPase activity, affects the alterations of redox state, and participates in the reestablishment of peripheral cholinergic activity during demyelinating and remyelination events.

The aim of this study was to evaluate whether injectable zinc and copper affect host immune responses and antioxidant status of newborn calves. For this study, 19 newborn calves were divided into two groups. The control group consisted of 10 animals; and the treated group consisted of nine animals that received copper edetate (Cu-ed) and zinc edetate (Zn-ed) subcutaneously at the first day of life at doses of 0.3 mg/kg and 1.0 mg/kg respectively. Blood and faecal samples were collected for laboratory analyses (seric biochemistry, proteinogram, antioxidant enzymes and parasitological examination) on days 10, 20 and 30 after birth. On day 10, treated animals showed increased levels of total proteins, as well as increased globulin levels compared to the control group, a finding probably related to the increase in ceruloplasmin and IgG heavy chain. Thirty days after mineral metaphylactic administration, IgG light chain and acid glycoprotein levels significantly increased in treated animals (p < .05). There were no significant differences between groups regarding the biochemical analyses (triglycerides, cholesterol, glucose and urea). On the other hand, the superoxide dismutase and catalase activities increased on day 10 after treatment. In the control group, eight animals showed severe diarrhoea and one died 8 days after birth. Two animals from this group showed mild diarrhoea. Only three treated animals had severe diarrhoea, and six showed signs of mild diarrhoea. All animals that showed severe diarrhoea (control = 8; treated = 3) had hyperthermia (over 39.5°C), and therefore, antibiotic therapy was administered (sulfadiazine and trimethoprim) for five consecutive days. In summary, Zn-ed and Cu-ed decreased the frequency and intensity of diarrhoea, modulated superoxide dismutase (SOD) and catalase (CAT) enzymes and also heightened the immune responsiveness of newborn calves, suggesting a new approach to improve cattle performance and minimize the occurrence of diarrhoea.

Some challenge has been faced by farmers and among them are the decline of animal performance and mortality rate in the growth phase. One of the main causes of low performance is gastrointestinal problems, most of them caused by parasitic infections. Among the protozoa of major importance that affect the poultry in the first weeks of life, stands out the genus Eimeria, a parasite that causes intestinal malabsorption. The current study used 40 chicks, 1-day old, separated into four groups that received the same diet with different levels of yucca extract and glutamine supplementation. The animals were weighed at 10 and 15 days of age, where five chicks per group were used to evaluate the presence of oocysts, intestinal lesions, and biochemical variables. The addition of glutamine and yucca extract caused positive effect controlling coccidiosis, decreasing the presence of oocysts in both periods (Friedman = 37; p = 0.001); in addition, both served to protect the gut against the injury caused by the infection. Increased total protein values on day 15 (Friedman = 12; p

The exposure to environmental stressors, such as organophosphate (OP) pesticides, has been associated with the development of neurodegenerative diseases. Chlorpyrifos (CPF) is the worldwide most used OP pesticide and one of the most hazardous pesticides as it can cross the blood-brain barrier. Since studies evaluating the effects of CPF on brain immune cells are scarce, this research investigated the oxidative and inflammatory responses of CPF exposure in murine microglial cells. BV-2 cells were exposed to different concentrations of CPF pesticide (0.3–300 μM). CPF induced activation of microglial cells, confirmed by Iba-1 and CD11b marking, and promoted microglial proliferation and cell cycle arrest at S phase. Moreover, CPF exposure increased oxidative stress production (NO, MDA, and O2∙), and upregulated pro-inflammatory cytokines (IL-1β and NLRP3) genes expression in BV-2 cells. Overall, data showed that CPF exposure, at the lowest concentrations, acted by promoting pro-oxidative and pro-inflammatory states in microglial cells. These results provide important information on the potential role of microglial activation in CPF-induced neuroinflammation and add to the expanding knowledge on the neurotoxicity of OP.

Diabetes mellitus (DM) is a metabolic disorder characterized by a chronic hyperglycemia state, increased oxidative stress parameters, and inflammatory processes. Aims To evaluate the effect of caffeic acid (CA) on ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) and adenosine deaminase (ADA) enzymatic activity and expression of the A2A receptor of the purinergic system, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymatic activity and expression of the α7nAChR receptor of the cholinergic system as well as inflammatory and oxidative parameters in diabetic rats. Methods Diabetes was induced by a single dose intraperitoneally of streptozotocin (STZ, 55 mg/kg). Animals were divided into six groups (n = 10): control/oil; control/CA 10 mg/kg; control/CA 50 mg/kg; diabetic/oil; diabetic/CA 10 mg/kg; and diabetic/CA 50 mg/kg treated for thirty days by gavage. Results CA treatment reduced ATP and ADP hydrolysis (lymphocytes) and ATP levels (serum), and reversed the increase in ADA and AChE (lymphocytes), BuChE (serum), and myeloperoxidase (MPO, plasma) activities in diabetic rats. CA treatment did not attenuate the increase in IL-1β and IL-6 gene expression (lymphocytes) in the diabetic state; however, it increased IL-10 and A2A gene expression, regardless of the animals' condition (healthy or diabetic), and α7nAChR gene expression. Additionally, CA attenuated the increase in oxidative stress markers and reversed the decrease in antioxidant parameters of diabetic animals. Conclusion Overall, our findings indicated that CA treatment positively modulated purinergic and cholinergic enzyme activities and receptor expression, and improved oxi-inflammatory parameters, thus suggesting that this phenolic acid could improve redox homeostasis dysregulation and purinergic and cholinergic signaling in the diabetic state.

Lambs born from dairy ewes are removed from their mothers within hours of ingesting colostrum; this influences their growth and development, especially when artificial milk has poor quality or insufficient volume. Alternatives have been proposed to assist lambs during this phase, including providing concentrate with additives such as choline, which is involved in various physiological processes. This study's objective was to determine the effects of vegetable biocholine (VB) supplementation on growth, biochemistry, and antioxidant responses in lambs from dairy ewes during the feed transition period. We used 40 Lacaune lambs in a randomized block design, distributed in four groups with five replications (two animals per replication). VB was added to the concentrate and was consumed between 30 days pre-weaning to 30 days post-weaning (total 60 days). The treatments were as follows: T0, without added VB, control group; T2, 2 g VB per animal/day; T4, 4 g VB per animal/day; and T6, 6 g VB per animal/day. The weight gain increased in T2, T4, and T6 lambs when compared to T0. Using orthogonal polynomials analysis suggested that the ideal supplementation dose is 2.81 g/day per animal when considering the maximum average daily gain (ADG), which corresponds to 0.189 g VB/kg of body weight (BW). After weaning, there were lower serum concentrations of creatine kinase enzyme in lambs supplemented with VB than in controls. No differences were observed concerning levels of total protein, albumin, or globulins. Alanine aminotransferase (ALT) activity of T2 and T4 lambs was greater only at weaning (30 days). Glucose was greater in T2 and T4 lambs only on day 15. In general, VB supplementation decreased serum levels of reactive oxygen species (ROS) from day 15 of supplementation; these animals had lower lipid peroxidation levels after weaning. The activities of glutathione S-transferase (GST) did not differ. These data suggest that supplementation with VB increases weight gain and improves health, primarily by reducing free radical levels during the dietary transition period.

Bovine brucellosis is an important zoonotic disease caused by the bacterium Brucella abortus that leads to economic losses due to animal discard and commercial restrictions. Since positive animals for brucellosis are culled, little is known about the pathogenesis of this disease. Therefore, the aims of this study were to evaluate possible changes in the activity of deaminase adenosine (ADA) and the oxidative stress in cows seropositives for brucellosis (Experiment I), and to evaluate the seroprevalence of B. abortus in dairy cows from the Western state of Santa Catarina, Southern Brazil (Experiment II). The Experiment I evaluated 20 pregnant cows: ten seropositives for B. abortus and ten seronegatives that were used as controls. The ADA activity and markers of oxidative stress (TBARS, catalase (CAT) and superoxide dismutase (SOD)) were evaluated in these animals. A reduction in the activity of ADA and catalase enzymes in seropositive animals was observed (p < 0.001). Conversely, there was an increase in TBARS levels and superoxide dismutase activity in cows infected by B. abortus (p < 0.001). The presence of oxidative stress and a reduction of ADA might be related to the modulation of the inflammatory response. The experiment II was performed due to a high number of herds with restrictions imposed by cases of brucellosis in the state of Santa Catarina in the last two years, and thus, the seroprevalence for B. abortus was evaluated in 1242 serum samples of cows of 69 herds. The serodiagnosis was performed using two tests: buffered acidified antigen and 2-mercaptoethanol. However, none of the serum samples were positive for B. abortus. Although we did not find seropositive animals for brucellosis in our study, the disease still requires continued surveillance, due to its economic impact, and to the oxidative stress caused by it, which may have contributed to cases of abortion in three seropositive cows (Experiment I) in the final third of the gestation.

A new series of 3,6-disubstituted 2-(methylthio)-4-(trifluoromethyl)-3,4-dihydropyrimidin-4-ols displaying methyl, phenyl, aryl, and heteroaryl groups at the 6-position; and methyl, ethyl, allyl, and phenyl groups at the 3-position of the dihydropyrimidine ring, were synthesized and evaluated in vitro for acetylcholinesterase (AChE) inhibitory activity. Seven compounds showed activity with IC50 values in the lower micromolar range. The compound 4-trifluoromethyl-6-(4-fluorophenyl)-3-methyl-2-methylthio-3,4-dihydropyrimidin-4-ol (6e) had the best inhibitory activity (IC50 2.2±0.9 μM) and this inhibition was characterized as competitive. The molecular docking study showed that the AChE enzyme accommodates compound 6e in its catalytic site. The enantiomers of compound 6e, present similar interactions: π–π stacking interactions between the aromatic ring of the ligand's 4-fluorophenyl moiety and the aromatic rings of the electron-rich Trp84; and H-bonds between the hydroxyl group of Tyr121 and the hydroxyl moiety from 6e. The antioxidant effect of the dihydropyrimidin-4-ols was also investigated. This article is protected by copyright. All rights reserved.