Grapiprant or carprofen following ovariohysterectomy in the cat: analgesic efficacy, hematological, biochemical and urinalysis evaluation.

OBJECTIVES: This study aimed to compare the analgesic effect between carprofen and grapiprant every 12 or 24 h on postoperative pain in cats undergoing ovariohysterectomy, in addition to the effects on the hematological, biochemical and urinalysis variables. METHODS: A total of 32 female cats were randomly divided into three groups, according to the treatment administered with the first dose given orally 90 mins before surgery, as follows: CAR (cats received 4 mg/kg carprofen, n = 11); GRA1 (cats received 2 mg/kg grapiprant, n = 10); and GRA2 (cats received 2 mg/kg grapiprant q12h, n = 11). Pain was assessed by UNESP-Botucatu Multidimensional Composite Pain Scale (UNESP) and Glasgow Feline Composite Measure Pain Scale (GLASGOW) for cats preoperatively (baseline) and at 1, 3, 6, 8, 12 and 24 h after extubation. Venous blood was collected at baseline, and 12 and 24 h after the administration of carprofen or grapiprant to perform a complete blood count (CBC), the percentage of Heinz bodies and serum biochemistry (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase, creatinine and urea). Urinalysis was performed at baseline and 24 h after extubation. Glucose levels were evaluated at baseline and 1 h postoperatively. RESULTS: Pain scores were not significantly different among groups in both scales, although pain was higher at 3 h in comparison with 24 h in all groups. In the GRA1 and GRA2 groups, 67% (14/21) of cats needed rescue analgesia compared with 18% (2/11) in the CAR group. Glucose increased from baseline to 1 h in the GRA1 and GRA2 groups. None of the CBC, serum biochemistry and urinalysis variables differed among groups. CONCLUSIONS AND RELEVANCE: Grapiprant did not promote adequate analgesia during the first 3 h postoperatively in cats undergoing ovariohysterectomy compared with carprofen, and no benefits were observed by administering grapiprant every 12 h.

Adapted technique for demonstrating argyrophilic nucleolar organizer regions in the cytologic samples of canine mast cell tumors.

INTRODUCTION: Argyrophilic nucleolar organizer regions (AgNORs) are nonhistone argyrophilic nucleolar proteins associated with ribosomal genes found in the nucleolar organizer region that reflect cell proliferation and have an affinity for silver. AgNOR staining may be useful to evaluate prognosis in several neoplasms because higher AgNOR counts are related to higher grade tumors, metastases, and shorter survival times. OBJECTIVE: We aimed to report on a quick and practical technique to identify AgNORs adapted for use in routine cytology. MATERIALS AND METHODS: The cytopathologic diagnosis of mast cell tumor (MCT) in samples collected by fine-needle aspiration (FNA) was determined. Next, slides were impregnated with a solution containing silver nitrate; the main modification of our technique included incubation of these slides at a controlled temperature of 25 °C. Some slides were previously stained with Diff-Quik and others were only fixed with methanol. The slides were analyzed under a microscope, and the number of blackened intranuclear points (AgNORs) was counted. RESULTS: Slides prestained with Diff-Quik were easily counted compared with slides only fixed in methanol. Technical issues encountered with the methanol-fixed slides included insufficient cellularity, background precipitation, and an absence of silver impregnation. CONCLUSIONS: The technique reported in this study showed satisfactory results for AgNOR counting in cytologic smears from MCT, such as good impregnation and the elimination of background interferents. Further evaluation of this method comparing AgNOR counts with histologic examinations, tumor grades, other prognostic markers, and survival times are needed to fully evaluate the benefit of this technique.

Amikacin prevents platelet aggregation in feline venous blood samples.

INTRODUCTION: Physiologically, feline platelets are more reactive and prone to aggregation, which interferes with platelet counts using automated counters and manual methods. The use of aminoglycoside amikacin in association with EDTA has proven to be efficient in preventing platelet aggregates in cases of pseudo thrombocytopenia (PTP) in people. OBJECTIVES: This study evaluated the efficacy of amikacin in preventing platelet aggregation in EDTA-containing feline blood samples and investigated the possible effects on hematologic measurands. MATERIALS AND METHODS: Blood samples (1.0 mL) collected from 100 healthy cats were stored in two EDTA tubes: 0.5 mL in a microtube containing 10 µL of 250 mg/mL amikacin (EDTA-AMK group) and 0.5 mL in a microtube containing only K2 EDTA 10% (EDTA group). A CBC was executed with an automated impedance blood analyzer, and a microscopic examination of the blood smears was performed. RESULTS: Platelet clumps were observed in 56% of samples from the EDTA group and 5% of samples from the EDTA-AMK group. Platelet counts (PLT), plateletcrit (PCT), and WBC counts were significantly higher (P < .001) in the EDTA-AMK group compared withi the EDTA group. CONCLUSIONS: Amikacin prevents platelet aggregation in feline venous blood samples and does not cause clinically relevant changes in other hematologic measurands. To our knowledge, this is the first report showing the use of amikacin in preventing platelet aggregation in feline blood samples. Based on this study, amikacin could be added to EDTA collection tubes for complete blood counts in cats.

Effects of Heated Pneumoperitoneum on Inflammation, Oxidative Stress, and Peritoneal Histology in Female Dogs That Underwent Video-Assisted Ovariohysterectomy.

Laparoscopic procedures require the creation of pneumoperitoneum. CO2, which must be cold and dry, is the standard gas used in such surgeries. The type of gas used, its temperature, and moisture may change the peritoneal surface and cause systemic and local oxidative stress. Our objective is to evaluate the influence of pneumoperitoneum heating on the occurrence of histological lesions in the peritoneum, inflammation, plasma oxidative stress, and on the mesothelial surface in patients undergoing video-assisted ovariohysterectomy. Twenty canine females were included and distributed evenly into two groups: heated CO2 (HG) and unheated CO2 (UHG). The biomarkers of inflammation and oxidative stress were evaluated before insufflation (T0), at 30 min (T1), and at 60 min (T2) of exposure to CO2. Biopsies of the peritoneal tissue for histological evaluation were performed at T0 and T2. Regarding plasma parameters, acetylcholinesterase (AChE) showed a greater activity in the HG at T1 (p=0.0268) and T2 (p=0.0423); in turn, butyrylcholinesterase (BChE) showed a greater activity at T2 in the HG (p=0.0175) compared with T0. Catalase activity (CAT) was different between HG times; it was higher at T1 (p=0.0253). There was a decrease in the levels of substances reactive to thiobarbituric acid (TBARS) (p=0.0117) and in glutathione (GSH) (p=0.0114) between T0 and T2 in the UHG. Regarding tissue oxidative stress, the CAT in the HG showed a greater activity at T2 than T1 (p=0.0150). By comparing the groups at each time, there was a difference only at T2 (p=0.0288), being greater in the HG. Regarding the activity of superoxide dismutase (SOD) in the HG, there was a difference between T2 in relation to T0 and T1 (p=0.0181); finally, there was an increase only at T1 (p=0.0287) in the UHG when comparing groups at the same time. There were no differences in the histological parameters evaluated. Our study demonstrates that the heating of CO2 generates a greater inflammatory response and forms reactive oxygen species (ROS) at the plasma and peritoneal levels.

Lipotoxicity-associated inflammation is prevented by guarana (Paullinia cupana) in a model of hyperlipidemia.

Hyperlipidemia causes lipotoxicity which prompts an inflammatory response linked to the development of cardiovascular diseases. Natural compounds have been receiving special attention for its potential to treat diseases, inexpensiveness, and safety. Guarana (Paullinia cupana) has demonstrated notable anti-inflammatory and antioxidant effects, which may prevent chronic diseases caused by changes in lipid profile. Thus, this study aims to evaluate the effect of guarana powder (Paullinia cupana) in the purine metabolism and inflammatory profile in lymphocytes and serum of rats with Poloxamer-407-induced hyperlipidemia. Pretreatment with guarana 12.5, 25, and 50 mg/kg/day or caffeine (0.2 mg/kg/day) by gavage was applied to adult male Wistar rats for a period of 30 days. As a comparative standard, we used simvastatin (0.04 mg/kg) post-induction. Hyperlipidemia was acutely induced with intraperitoneally injection of Poloxamer-407 (500 mg/kg). Guarana powder and caffeine increased the activity of the E-NTPDase (ecto-apyrase), and all pretreatments decreased the E-ADA (ecto-adenosine deaminase) activity, reducing the inflammatory process caused by lipotoxicity. In hyperlipidemic rats, ATP levels were increased while adenosine levels were decreased, guarana and caffeine reverted these changes. Guarana powder, caffeine, and simvastatin also prevented the increase in INF-γ and potentiated the increase in IL-4 levels, promoting an anti-inflammatory profile. Guarana promoted a more robust effect than caffeine. Our results show that guarana powder and caffeine have an anti-inflammatory as seen by the shift from a proinflammatory to an anti-inflammatory profile. The effects of guarana were more pronounced, suggesting that guarana powder may be used as a complementary therapy to improve the lipotoxicity-associated inflammation.

Uncaria tomentosa improves cognition, memory and learning in middle-aged rats.

Aging accelerates neurodegeneration, while natural and safe neuroprotective agents, such as Uncaria tomentosa, may help to overcome this problem. This study assessed the effects of U. tomentosa extract treatment on the aging process in the brain of Wistar rats. The spatial memory and learning, acetylcholinesterase (AChE) activity, and DNA damage were assessed. Animals of 14 months were tested with different doses of U. tomentosa (5 mg/kg, 15 mg/kg, and 30 mg/kg) and with different durations of treatment (one month and one year). In the Morris Water Maze (MWM), the escape latency was significantly (p < 0.0001) shorter in rats that received 5 mg/kg, 15 mg/kg, and 30 mg/kg of U. tomentosa for both one month and one year of treatment. There was a significant difference in time spent at the platform zone (p < 0.05) of the middle-aged rats treated with U. tomentosa extract for one year when compared to the control rats. The cortex and hippocampus of rats treated with U. tomentosa for one year showed significant (p > 0.05) reduction in AChE activity. DNA damage index on cortex was significantly lower (p < 0.05) in animals treated with 30 mg/kg of U. tomentosa for one month while all the tested doses demonstrated significant (p < 0.001) reductions in DNA damage index in animals treated for one year. In conclusion, U. tomentosa may represent a source of phytochemicals that could enhance memory activity, repair DNA damage, and alter AChE activity, thereby providing neuroprotection during the aging process.

Impacts of dose and length of exposure to boldenone and stanazolol on enzymatic antioxidant systems, myeloperoxidase and NAGase activities, and glycogen and lactate levels in rat liver.

We investigated the adverse effects of the anabolic androgenic steroids (AAS) boldenone (BOL) and stanazolol (ST) on the enzymatic antioxidant systems of the rat liver. Male Wistar rats were divided in three protocols (P): PI, 5 mg/kg BOL or ST once a week for 4 weeks; PII, 2.5 mg/kg BOL or ST once a week for 8 weeks; PIII, 1.25 mg/kg BOL or ST once a week for 12 weeks. AAS were administered intramuscularly (0.2 ml, olive oil vehicle) once a week in all protocols. Activities of the enzymes glutathione peroxidase (GPx), glutathione S-transferase (GST), and glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), were investigated. We assessed the content of hydrogen peroxide (H2O2), glycogen and lactate; and enzyme markers of neutrophils (myeloperoxidase, MPO) and macrophages (NAGase). PI and PII altered the SOD and CAT activities and increased the H2O2 content. PI led to increases in the MPO and NAGase activities. In contrast, changes in GPx, GST and, GR were observed under PII and, to a greater extend, under PIII. Following PIII, GPx, GR, and GST exhibited reduced activities. All protocols altered the glycogen and lactate content. The use of high doses of AAS for a short duration first alters SOD/CAT activity. In contrast, at lower doses of AAS for long periods is associated with changes in the glutathione system. Protocols with high doses of AAS for a short duration exert the most deleterious effects on redox status, markers of cellular infiltration, and the metabolic functioning of hepatic tissues.

Aluminum-induced alterations of purinergic signalling in embryonic neural progenitor cells.

The ubiquitous presence of aluminum in the environment leads to a high likelihood of human exposure. Neurotoxicity of the trivalent cationic form of this metal (Al3+) occurs in the central nervous system via accumulation of Al in cells of neural origin, including neural progenitor cells (NPCs). NPCs play a key role in the development and regeneration of the brain throughout life; therefore, this metal may contribute to neuropathological conditions. Here, we evaluated the effects of different Al3+ concentrations (0-50 µM) on the purinergic system of NPCs isolated from embryonic telencephalons, cultured as neurospheres. Al3+ adhered to the cell surface of neurospheres reducing extracellular ATP release, as well as ATP, ADP, and AMP hydrolysis by NTPDase and 5'-nucleotidase, respectively. In addition, impaired nucleotide release by Al3+ reduced P2Y1 and adenosine A2A receptors expression in differentiated neurospheres. These receptors are crucial for NPC proliferation during brain development and self-repair against external stimuli, such as metal exposure. Thus, Al3+ represents an environmental agent linked to neurodegeneration through alterations in the ATP-signalling pathway, proving to be a potential mechanism associated with NPC proliferation and brain degeneration.

Changes in cardiac and hepatic energetic metabolism in gerbils infected by Listeria monocytogenes.

Energy metabolism is a sensitive indicator of cellular disorders. Therefore, the objective of this study was to investigate changes in cardiac and hepatic energy metabolism during listeriosis using an experimental model. We divided gerbils into two groups: Control (n = 11) and orally Infected (n = 12) with 5 × 109 CFU/mL of Listeria monocytogenes. Euthanasia and sampling were performed on days 6 and 12 post-infection (PI). Histopathological lesions were not found in the heart; however, the liver showed pyogranuloma. In the hearts of infected animals, cytosolic creatine kinase activity was lower on day 6 and 12 PI; mitochondrial creatine kinase/pyruvate kinase (PK), and sodium potassium pump (Na+/K+-ATPase) activities were lower on day 12 PI. Hepatic PK and Na+/K+-ATPase activities were lower in the infected group on day 12 PI. Lipoperoxidation was higher in the livers and hearts of infected animals on day 12 PI, and antioxidant capacity against peroxyl radicals (ACAP) was also higher in this group. These data suggest that subclinical listeriosis alters hepatic and cardiac energy metabolism, possibly related to decreased activity of phosphotransferases and ATPase. Subsequent antioxidant responses are not sufficient to correct alterations in lipid peroxidation and bioenergetics, possibly leading to important cellular pathological mechanisms.

Evaluation of postoperative pain and toxicological aspects of the use of dipyrone and tramadol in cats.

OBJECTIVES: The aim of this study was to evaluate the effects of dipyrone and tramadol, used for 5 days, on postoperative pain, hematological and biochemical parameters, and oxidative markers on erythrocytes. METHODS: Twenty-eight healthy cats underwent ovariohysterectomy and were randomly allocated to four groups (each n = 7), according to the postoperative treatment administered intravenously: control (saline 1 ml q8h), DIP1 (dipyrone 25 mg/kg q24h), DIP2 (dipyrone 25 mg/kg q12h) and DIP3 (dipyrone 25 mg/kg q8h). All animals received tramadol (2 mg/kg q8h). Pain was assessed by visual analog (VAS), multidimensional UNESP and Glasgow pain scales for cats preoperatively and at 3, 6, 12, 24, 36 and 48 h after extubation. Venous blood was collected daily for 5 days, and on day 10, to perform a complete blood count (CBC) and determine the percentage of Heinz bodies (HBs). Serum biochemistry was evaluated preoperatively and on days 5 and 10; superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO) and lipoperoxidation were evaluated preoperatively and on days 3, 5 and 10. RESULTS: Control cats had higher pain scores than DIP3 cats by UNESP (P = 0.0065), and DIP2 (P = 0.0035) and DIP3 cats (P = 0.0108) by VAS 3 h postoperatively. Rescue analgesia was required by two animals in the control group and one each in the DIP1 and DIP2 groups. There was no difference in SOD or CAT among groups. On day 5, MPO was more active in DIP2 than in DIP3 cats (P = 0.0274). No difference in lipoperoxidation among treatment and control cats was found. CBC remained constant and without statistical difference among groups. Control, DIP2 and DIP3 cats presented a similar percentage of HBs on day 10. Biochemical variables were similar among groups and times. CONCLUSIONS AND RELEVANCE: The administration of dipyrone in cats, when used in combination with tramadol, did not ensure better analgesia than tramadol alone. Dipyrone did not significantly affect biochemical variables and oxidative markers, despite minimal, clinically irrelevant, hematological differences between groups.

Astrocaryum aculeatum fruit improves inflammation and redox balance in phytohemagglutinin-stimulated macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Astrocaryum aculeatum G.Mey. (tucumã) is highly consumed by riverside communities in the Amazonian region. These communities have recently been shown to have increased longevity and reduced prevalence of age-related morbidity. Tucumã, which is locally used in their diet and traditional medicine may contribute to these features. AIM OF THE STUDY: To investigate the anti-inflammatory and antioxidant properties of A. aculeatum extract against phytohemagglutinin-induced inflammation in cell cultures. MATERIALS AND METHODS: Cell viability and cytotoxicity assays, gene expression of interleukins IL-1ß, IL-6, IL-10, levels of reactive oxygen species (ROS), nitric oxide (NO) and thiols were employed, as well as the activities of antioxidant enzymes in RAW 264.7 cells stimulated with phytohemagglutinin to mimic inflammation. RESULTS: The extract of A. aculeatum fruit inhibited macrophage proliferation (P < 0.05), arrested the cell cycle in G0/G1 phase (P < 0.001), increased antioxidant defenses (P < 0.01), reduced oxidative stress (P < 0.01), and modulated genes related to the inflammatory response (P < 0.001). CONCLUSION: Our results demonstrate that A. aculeatum fruit has anti-inflammatory and antioxidant capacities. These beneficial effects of tucumã on cells are also likely to be seen in vivo, thereby suggesting that its extract is a suitable therapeutic adjuvant in the prevention or treatment of inflammatory diseases.

Trypanosoma evansi impacts on embryonic neural progenitor cell functions.

Trypanosoma evansi appears to have a significant tropism for brain tissue in its chronic and acute phases. The most common symptoms of this brain infection are motor incoordination, meningoencephalitis, demyelination, and anemia. There have only been few studies of the effects of T. evansi infection on neuronal differentiation and brain plasticity. Here, we investigated the impact of the congenital T. evansi infection on brain development in mice. We collected telencephalon-derived neural progenitor cells (NPCs) from T. evansi uninfected and infected mice, and cultivated them into neurospheres. We found that T. evansi significantly decreased the number of cells during development of neurospheres. Analysis of neurosphere differentiation revealed that T. evansi infection significantly increased neural migration. We also observed that T. evansi promoted expression of glial fibrillary acidic protein (GFAP) in infected cells. These data suggest that congenital T. evansi infection may affect embryonic brain development.

Aluminum affects neural phenotype determination of embryonic neural progenitor cells.

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 ß3-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.

Effect of free and nano-encapsulated curcumin on treatment and energetic metabolism of gerbils infected by Listeria monocytogenes.

Bacterial infections require special care since the indiscriminate use of antibiotics to treat them has been linked to the emergence of resistant strains. In this sense, phytoterapeutic alternatives such as curcumin and its nanocapsules have emerged as a promising supplement in optimizing availability of bioactives and reducing the development of antimicrobial resistance. Thus, the aim of this study was to verify the effects of pure and nanoencapsulated curcumin in the treatment of experimental listeriosis in gerbils regarding many aspects including antibacterial effect, antioxidant mechanisms involved and the energetic metabolism. Four groups were used containing 6 animals each: T0 (control), T1 (infected), T2 (infected and treated with free curcumin - dose of 30 mg/kg/day) and T3 (infected and treated with nanocapsules containing curcumin - a dose of 3 mg/kg/day). Treated animals received curcumin for 6 consecutive days starting 24 h after Listeria monocytogenes infection. All animals were euthanized on the 12th day after L. monocytogenes infection. Quantitative polymerase chain reaction (qPCR) identified L. monocytogenes DNA in the spleens of all animals of the T1 group, as well as T2 (2 out of 6) and T3 (5 out of 6). The weight of the spleens confirmed the infection, since it was larger in the T1 group, differing statistically from T0, and similarly to T2 and T3. Hepatic histopathological examination showed mild infiltration of neutrophils and macrophages, except for the T3 group (only 1/6). In the liver, the pyruvate kinase activity was higher in T1 and T2 compared to T0 and T3. The adenylate kinase activity did not differ between groups. The Na+/K+ATPase activity was lower in T1 group compared to T0 and T3. Lipoperoxidation was lower in the T3 group compared to groups T0, T1 and T2. The antioxidant capacity against peroxyl radicals was higher in T1, T2 and T3 groups compared to T0. In conclusion, free curcumin showed potent antibacterial effects; however, the nanoencapsulated form was able to minimize the effects caused by L. monocytogenes regarding tissue injury, changes on enzymes of the energetic metabolism, in addition to an antioxidant effect against lipoperoxidation.

Curcumin pre-treatment modulate the activities of adenine nucleotide and nucleoside degradation enzymes in lymphocyte of rats infected with Trypanosoma evansi.

This study aimed to evaluate nucleoside triphosphate diphosphohydrolase (NTPDase) and adenosine deaminase (ADA) activities in lymphocytes from rats supplemented or not with curcumin 30 days prior to experimental infection with Trypanosoma evansi. Thirty-two adult male Wistar rats were divided in four groups. The pre-infection group 20 (PreI20) received orally 20 mg/kg of curcumin and pre-infection group 60 (PreI60) received orally 60 mg/kg of curcumin for 30 days prior inoculation with T. evansi. The infected e non-infected control groups received only oral vehicle for 30 days. Trypanosoma evansi infected groups were inoculated intraperitoneally with 0.2 ml of blood with 1 × 106 parasites. After inoculation the treatment of the groups continued until the day of euthanasia (15 days). The results showed that curcumin pre-treatment, with both doses, reduced (P < .05) NTPDase and increased (P < .05) ADA activity in lymphocytes of treated groups when compared to untreated and infected animals (control). The results of this study support the evidence that the regulation of ATP and adenosine levels by NTPDase and ADA activities appear to be important to modulate the immune response in T. evansi infection, once the treatment with curcumin maintained the NTPDase activity reduced and enhanced ADA activity in lymphocytes. It is possible to conclude that the use of curcumin prior to infection with T. evansi induces immunomodulatory effects, favoring the response against the parasite.

Effects of resveratrol on the differentiation fate of neural progenitor cells of mouse embryos infected with Trypanosoma cruzi.

Chagas disease (CD) affecting about 7 million people is caused by the flagellate protozoan Trypanosoma cruzi. The central nervous system (CNS) is an important site for T. cruzi persistence in the host during the chronic phase of infection, because the protozoan may pass the blood-brain barrier and may cause motor and cognitive neuronal damage. Thinking about avoiding or minimizing these negative effects, it is hypothesized that resveratrol (RSV), a component with several medicinal properties has beneficial effects on the CNS. The objective of this study was to investigate, whether T. cruzi infection interferes with neurogenesis and gliogenesis of embryos of infected mice females, and whether RSV would be able to avoid or minimize these changes caused by CD. RSV is a polyphenol found in grapes and widely studied for its neuroprotective and antioxidant properties. In addition, we investigated the role caused by the parasite during congenital infection and CNS development. Embryos and their brains were PCR-positive for T. cruzi. For this study, NPCs obtained from telencephalon of infected and uninfected embryos and were cultured in presence of resveratrol for forming neurospheres. The results demonstrated that the congenital transmission of T. cruzi influences CNS formation and neural fate, decreasing the number of neuroespheres and causing an elongation in the phases of the cell cycle. In addition, the parasite promoted an increase in neugliogenesis. Resveratrol was neuroprotective and prevented negative effects of the infection. Thus, we suggest the use of resveratrol as a therapeutic target for the treatment of neuroinflammation or as neuroprotective agent during Chagas disease, as it improves gliogenesis and restores neural migration.

Rutin and curcumin reduce inflammation, triglyceride levels and ADA activity in serum and immune cells in a model of hyperlipidemia.

Hyperlipidemia is associated with endothelial dysfunction and inflammatory disorders. Adenosine and adenosine deaminase (ADA) modulate immune responses and lipid metabolism. Curcumin and rutin are polyphenols with antioxidant, anti-inflammatory, and hypolipidemic effects. We evaluated the action of rutin and curcumin in the lipid levels and inflammation, as well as their effect on ADA activity in serum, lymphocytes, platelets, and neutrophils of hyperlipidemic rats. Adult male Wistar rats pretreated with curcumin and/or rutin for 30 days were submitted to Poloxamer-407- induced hyperlipidemia. Biochemical, hematological, and oxidative stress parameters, as well as serum and extracellular ADA activity, were performed 36h post-induction. Hyperlipidemia was confirmed by the increase in total cholesterol (TC) and triglycerides (TG). Hematological alterations, elevated reactive oxygen species (ROS) levels, and increased myeloperoxidase (MPO) and ADA activities were observed in hyperlipidemic rats. Curcumin and the curcumin/rutin association decreased TG and increased high-density lipids (HDL) levels. The pretreatments prevented changes in the hematological parameters, decreased the activities of MPO in plasma and ADA in serum and cells. Cholesterol and ROS levels were not altered by the pretreatments. Our results show that pretreatments with rutin and/or curcumin prevent the hyperlipidemia-induced inflammation. Pretreatments with curcumin and/or rutin are potential complementary therapies in the prevention of hypertriglyceridemia and inflammation.

A phytochemical study of the Cuphea glutinosa from Southern Brazil: Na+,K+-ATPase activity inhibition and antioxidant properties.

This study investigated the antioxidant activity of Cuphea glutinosa (CG) and its effect on Na+, K+-ATPase from cardiac muscle. The ethanolic extract showed higher antioxidant capacity compared to aqueous and ethyl acetate fraction. Ethyl acetate fraction showed ß-sitosterol-3-O-ß-glucoside, kaempferol, quercetin, isoquercetin, gallic acid methyl ester, and gallic acid. The ethanolic extract also reduced the Na+,K+-ATPase activity. CG presented a promising antioxidant activity and inhibitory effect on the Na+, K+-ATPase activity, supporting biochemical evidences the popular use of this plant in the treatment of heart failure.

Quercetin treatment regulates the Na+,K+-ATPase activity, peripheral cholinergic enzymes, and oxidative stress in a rat model of demyelination.

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.

A comparative study of the effect of the dose and exposure duration of anabolic androgenic steroids on behavior, cholinergic regulation, and oxidative stress in rats.

The aim of this study was to assess if the dose and exposure duration of the anabolic androgenic steroids (AAS) boldenone (BOL) and stanazolol (ST) affected memory, anxiety, and social interaction, as well as acetylcholinesterase (AChE) activity and oxidative stress in the cerebral cortex (CC) and hippocampus (HC). Male Wistar rats (90 animals) were randomly assigned to three treatment protocols: (I) 5 mg/kg BOL or ST, once a week for 4 weeks; (II) 2.5 mg/kg BOL or ST, once a week for 8 weeks; and (III) 1.25 mg/kg BOL or ST, once a week for 12 weeks. Each treatment protocol included a control group that received an olive oil injection (vehicle control) and AAS were administered intramuscularly (a total volume of 0.2 ml) once a week in all three treatment protocols. In the BOL and ST groups, a higher anxiety level was observed only for Protocol I. BOL and ST significantly affected social interaction in all protocols. Memory deficits and increased AChE activity in the CC and HC were found in the BOL groups treated according to Protocol III only. In addition, BOL and ST significantly increased oxidative stress in both the CC and HC in the groups treated according to Protocol I and III. In conclusion, our findings show that the impact of BOL and ST on memory, anxiety, and social interaction depends on the dose and exposure duration of these AAS.