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.

Pretreatment with quercetin prevents changes in lymphocytes E-NTPDase/E-ADA activities and cytokines secretion in hyperlipidemic rats.

Hyperlipidemia (HL) is a condition associated with endothelial dysfunction and inflammatory disorders. Purinergic system ectoenzymes play an important role in modulating the inflammatory and immune response. This study investigated whether the preventive treatment with quercetin is able to prevent changes caused by hyperlipidemia in the purinergic system, through the activities of E-NTPDase and E-ADA in lymphocytes, and quantify the nucleotides and nucleoside, and the secretion of anti- and proinflammatory cytokines. Animals were divided into saline/control, saline/quercetin 5 mg/kg, saline/quercetin 25 mg/kg, saline/quercetin 50 mg/kg, saline/simvastatin (0.04 mg/kg), hyperlipidemia, hyperlipidemia/quercetin 5 mg/kg, hyperlipidemia/quercetin 25 mg/kg, hyperlipidemia/quercetin 50 mg/kg, and hyperlipidemia/simvastatin. Animals were pretreated with quercetin for 30 days and hyperlipidemia was subsequently induced by intraperitoneal administration of 500 mg/kg of poloxamer-407. Simvastatin was administered after the induction of hyperlipidemia. Lymphocytes were isolated and E-NTPDase and E-ADA activities were determined. Serum was separated for the cytokines and nucleotide/nucleoside quantification. E-NTPDase and E-ADA activities were increased in lymphocytes from hyperlipidemic rats and pretreatment with quercetin was able to prevent the increase in the activities of these enzymes caused by hyperlipidemia. Hyperlipidemic rats when receiving pretreatment with quercetin and treatment with simvastatin showed decreased levels of ATP and ADP when compared to the untreated hyperlipidemic group. The IFN-γ and IL-4 cytokines were increased in the hyperlipidemic group when compared with control group, and decreased when hyperlipidemic rats received the pretreatment with quercetin. However, pretreatment with quercetin was able to prevent the alterations caused by hyperlipidemia probably by regulating the inflammatory process. We can suggest that the quercetin is a promising compound to be used as an adjuvant in the treatment of hyperlipidemia.

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

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

Sepsis induced by cecal ligation and perforation (CLP) alters nucleotidase activities in platelets of rats.

Sepsis is a potentially lethal condition, and it is associated with platelet alterations. The present study sought to investigate the activity of ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase), E-5'-nucleotidase, and ecto-adenosine deaminase (E-ADA) in the platelets of rats that were induced with sepsis. Male Wistar rats were divided into three groups of ten animals each: a negative control group (normal; NC); a group that underwent surgical procedures (sham); and a group that underwent cecal ligation and perforation (CLP). The induction of sepsis was confirmed by bacteremia, and the causative pathogen identified was Escherichia coli. Hematological parameters showed leukocytosis and thrombocytopenia in animals in the septic group. The results also revealed that there were significant (p < 0.05) increases in adenosine triphosphate (ATP) and adenosine monophosphate (AMP) hydrolyses, and in the deamination of adenosine in the CLP group compared to the sham and control groups. Conversely, ADP hydrolysis was significantly decreased (p < 0.05) in the CLP group compared to the sham and control groups. Purine levels were analyzed by high-performance liquid chromatography (HPLC) in serum samples from control, sham, and CLP groups. Increased concentrations of ATP, adenosine, and inosine were found in the CLP group compared to the sham and control groups. Conversely, the concentrations of ADP and AMP in the CPL group were not significantly altered. We suggest that alterations in hematological parameters, nucleotide hydrolysis in platelets, and nucleotide concentrations in serum samples of rats with induced sepsis may be related to thromboembolic events.

Guarana (Paullinia cupana) ameliorates memory impairment and modulates acetylcholinesterase activity in Poloxamer-407-induced hyperlipidemia in rat brain.

Hyperlipidemia is a risk factor for the development of cognitive dysfunction and atherosclerosis. Natural compounds have recently received special attention in relation to the treatment of disease due to their low cost and wide margin of safety. Thus, the aim of this study was to determine the possible preventive effect of guarana powder (Paullinia cupana) on memory impairment and acetylcholinesterase (AChE) activity in the brain structures of rats with Poloxamer-407-induced hyperlipidemia. Adult male Wistar rats were pretreated with guarana (12.5, 25 and 50mg/kg/day) and caffeine (0.2mg/kg/day) by gavage for a period of 30days. Simvastatin (0.04mg/kg) was administered as a comparative standard. Acute hyperlipidemia was induced with intraperitoneal injections of 500mg/kg of Poloxamer-407. Memory tests and evaluations of anxiety were performed. The cortex, cerebellum, hippocampus, hypothalamus and striatum were separated to assess acetylcholinesterase activity. Our results revealed that guarana powder was able to reduce the levels of TC and LDL-C in a manner similar to simvastatin. Guarana powder also partially reduced the liver damage caused by hyperlipidemia. Guarana was able to prevent changes in the activity of AChE and improve memory impairment due to hyperlipidemia. Guarana powder may therefore be a source of promising phytochemicals that can be used as adjuvant therapy in the management of hyperlipidemia and cognitive disorders.

Curcumin attenuates memory deficits and the impairment of cholinergic and purinergic signaling in rats chronically exposed to cadmium.

This study investigated the protective effect of curcumin on memory loss and on the alteration of acetylcholinesterase and ectonucleotidases activities in rats exposed chronically to cadmium (Cd). Rats received Cd (1 mg/kg) and curcumin (30, 60, or 90 mg/kg) by oral gavage 5 days a week for 3 months. The animals were divided into eight groups: vehicle (saline/oil), saline/curcumin 30 mg/kg, saline/curcumin 60 mg/kg, saline/curcumin 90 mg/kg, Cd/oil, Cd/curcumin 30 mg/kg, Cd/curcumin 60 mg/kg, and Cd/curcumin 90 mg/kg. Curcumin prevented the decrease in the step-down latency induced by Cd. In cerebral cortex synaptosomes, Cd-exposed rats showed an increase in acetylcholinesterase and NTPDase (ATP and ADP as substrates) activities and a decrease in the 5'-nucleotidase activity. Curcumin was not able to prevent the effect of Cd on acetylcholinesterase activity, but it prevented the effects caused by Cd on NTPDase (ATP and ADP as substrate) and 5'-nucleotidase activities. Increased acetylcholinesterase activity was observed in different brain structures, whole blood and lymphocytes of the Cd-treated group. In addition, Cd increased lipid peroxidation in different brain structures. Higher doses of curcumin were more effective in preventing these effects. These findings show that curcumin prevented the Cd-mediated memory impairment, demonstrating that this compound has a neuroprotective role and is capable of modulating acetylcholinesterase, NTPDase, and 5'-nucleotidase activities. Finally, it highlights the possibility of using curcumin as an adjuvant against toxicological conditions involving Cd exposure. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 70-83, 2017.

Cholinesterases as markers of the inflammatory process associated oxidative stress in cattle infected by Babesia bigemina.

The objective of this study was to assess the influence of an asymptomatic experimental infection by Babesia bigemina on cholinesterase's as markers of the inflammatory process and biomarkers of oxidative imbalance. For this purpose, eight naive animals were used, as follows: four as controls or uninfected; and four infected with an attenuated strain of B. bigemina. Blood samples were collected on days 0, 7 and 11 post-inoculation (PI). Parasitemia was determined by blood smear evaluation, showing that the infection by B. bigemina resulted in mean 0.725 and 0.025% on day 7 and 11 PI, respectively, as well as mild anemia. The activities of acetylcholinesterase, butyrylcholinesterase and catalase were lower, while levels of thiobarbituric acid reactive substances and superoxide dismutase activity were higher in infected animals, when compared with the control group. This attenuated strain of B. bigemina induced an oxidative stress condition, as well as it reduces the cholinesterasés activity in infected and asymptomatic cattle. Therefore, this decrease of cholinesterase in infection by B. bigemina purpose is to inhibit inflammation, for thereby increasing acetylcholine levels, potent anti-inflammatory molecules.

Effect of antiretroviral therapy in thromboregulation through the hydrolysis of adenine nucleotides in platelets of HIV patients.

The human immunodeficiency virus (HIV) infection results in biochemical and vascular dysfunctions. The highly active antiretroviral therapy (HAART) markedly reduces mortality and opportunistic diseases associated with acquired immunodeficiency syndrome (AIDS). This increased survival time predisposes the development of cardiovascular diseases. Platelets present purinergic system ectoenzymes such as E-NTPDase, E-5'-nucleotidase and E-ADA on its surface. In view of this, the aim of this study was to evaluate the activity of these ectoenzymes in platelets as well as the platelet aggregation and lipid profile of patients with HIV infection and also patients receiving HAART. The results showed an increase in the E-NTPDase activity for ATP hydrolysis in the HIV group compared with the control group and the HIV/HAART group. When assessing the activity E-NTPDase hydrolysis to ADP, the results revealed an increase in activity in the HIV group when compared to the control group, and a decrease in activity when in the HIV/HAART group when compared to the control and HIV groups. The activity of E-5'-nucleotidase revealed an increase in AMP hydrolysis in the HIV group, as the results from control and HIV/HAART groups showed no statistical difference. Regarding the E-ADA activity, the HIV and HIV/HAART groups revealed a decreased deamination of adenosine when compared with the control group. Furthermore, we observed an increased platelet aggregation of HIV/HAART group compared with the control group. Thus, our results suggest that antiretroviral treatment against HIV has a significant effect on the activity of purinergic system ectoenzymes demonstrating that thromboregulation is involved in the process.

NTPDase and 5'-nucleotidase activities in synaptosomes of rabbits experimentally infected with BoHV-5.

Bovine herpesvirus type 5 (BoHV-5) is the causative agent of herpetic meningoencephalitis in cattle. The purinergic system is described as a modulator of the immune response and neuroinflammation. These functions are related to the extracellular nucleotides concentration. NTPDase and 5'-nucleotidase are enzymes responsible for controlling the extracellular concentration of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine (ADO). The aim of this study is to determinate the ectonucleotidase activity in cortical synaptosomes and synaptosomes from the hippocampus of rabbits experimentally infected with BoHV-5. Rabbits were divided into four groups, two control groups (non-inoculated animals), and two infected groups (inoculated with BoHV-5). The infected groups received 0.5 ml of BoHV-5 suspension with 10(7.5)TCID50 of viral strain SV-507/99, per paranasal sinuses, and the control groups received 0.5 ml of minimum essential media per paranasal sinuses. Animals were submitted to euthanasia on days 7 and 12 post-inoculation (p.i.); cerebral cortex and hippocampus were collected for the synaptosomes isolation and posterior determination of the ectonucleotidase activities. The results showed a decrease (P < 0.05) in ectonucleotidase activity in synaptosomes from the cerebral cortex of infected rabbits, whereas an increased (P < 0.05) ectonucleotidase activity was observed in synaptosomes from the hippocampus. These differences may be related with the heterogeneous distribution of ectonucleotidases in the different brain regions and also with the viral infectivity. Therefore, it is possible to speculate that BoHV-5 replication results in changes in ectonucleotidase activity in the brain, which may contribute to the neurological signs commonly observed in this disease.

Anthocyanins suppress the secretion of proinflammatory mediators and oxidative stress, and restore ion pump activities in demyelination.

The aim of this study was to investigate the protective effect of anthocyanins (ANT) on oxidative and inflammatory parameters, as well as ion pump activities, in the pons of rats experimentally demyelinated with ethidium bromide (EB). Rats were divided in six groups: control, ANT 30 mg/kg, ANT 100 mg/kg, EB (0.1%), EB plus ANT 30 mg/kg and EB plus ANT 100 mg/kg. The EB cistern pons injection occurred on the first day. On day 7, there was a peak in the demyelination. During the 7 days, the animals were treated once per day with vehicle or ANT. It was observed that demyelination reduced Na(+),K(+)-ATPase and Ca(2+)-ATPase activities and increased 4-hydroxynonenal, malondialdehyde, protein carbonyl and NO2plus NO3 levels. In addition, a depletion of glutathione reduced level/nonprotein thiol content and a decrease in superoxide dismutase activity were also seen. The dose of 100 mg/kg showed a better dose-response to the protective effects. The demyelination did not affect the neuronal viability but did increase the inflammatory infiltrate (myeloperoxidase activity) followed by an elevation in interleukin (IL)-1ß, IL-6, tumor necrosis factor-α and interferon-γ levels. ANT promoted a reduction in cellular infiltration and proinflammatory mediators. Furthermore, ANT restored the levels of IL-10. Luxol fast blue staining confirmed the loss of myelin in the EB group and the protective effect of ANT 100 mg/kg. In conclusion, this study was the first to show that ANT are able to restore ion pump activities and protect cellular components against the inflammatory and oxidative damages induced by demyelination.

Quercetin protects the impairment of memory and anxiogenic-like behavior in rats exposed to cadmium: Possible involvement of the acetylcholinesterase and Na(+),K(+)-ATPase activities.

The present study investigated the effects of quercetin in the impairment of memory and anxiogenic-like behavior induced by cadmium (Cd) exposure. We also investigated possible alterations in acetylcholinesterase (AChE), Na(+),K(+)-ATPase and δ-aminolevulinate dehydratase (δ-ALA-D) activities as well as in oxidative stress parameters in the CNS. Rats were exposed to Cd (2.5mg/kg) and quercetin (5, 25 or 50mg/kg) by gavage for 45days. Animals were divided into eight groups (n=10-14): saline/control, saline/Querc 5mg/kg, saline/Querc 25mg/kg, saline/Querc 50mg/kg, Cd/ethanol, Cd/Querc 5mg/kg, Cd/Querc 25mg/kg and Cd/Querc 50mg/kg. Results demonstrated that Cd impaired memory has an anxiogenic effect. Quercetin prevented these harmful effects induced by Cd. AChE activity decreased in the cerebral cortex and hippocampus and increased in the hypothalamus of Cd-exposed rats. The Na(+),K(+)-ATPase activity decreased in the cerebral cortex, hippocampus and hypothalamus of Cd-exposed rats. Quercetin prevented these effects in AChE and Na(+),K(+)-ATPase activities. Reactive oxygen species production, thiobarbituric acid reactive substance levels, protein carbonyl content and double-stranded DNA fractions increased in the cerebral cortex, hippocampus and hypothalamus of Cd-exposed rats. Quercetin totally or partially prevents these effects caused by Cd. Total thiols (T-SHs), reduced glutathione (GSH), and reductase glutathione (GR) activities decreased and glutathione S-transferase (GST) activity increased in Cd exposed rats. Co-treatment with quercetin prevented reduction in T-SH, GSH, and GR activities and the rise of GST activity. The present findings show that quercetin prevents alterations in oxidative stress parameters as well as AChE and Na(+),K(+)-ATPase activities, consequently preventing memory impairment and anxiogenic-like behavior displayed by Cd exposure. These results may contribute to a better understanding of the neuroprotective role of quercetin, emphasizing the influence of this flavonoid in the diet for human health, possibly preventing brain injury associated with Cd intoxication.

Neuroprotective role of quercetin in locomotor activities and cholinergic neurotransmission in rats experimentally demyelinated with ethidium bromide.

AIM: The purpose of this study was to investigate whether the flavonoid quercetin can prevent alterations in the behavioral tests and of cholinergic neurotransmission in rats submitted to the ethidium bromide (EB) experimental demyelination model during events of demyelination and remyelination. MAIN METHODS: Wistar rats were randomly distributed into four groups (20 animals per group): Control (pontine saline injection and treatment with ethanol), Querc (pontine saline injection and treatment with quercetin), EB (pontine 0.1% EB injection and treatment with ethanol), and EB+Querc (pontine 0.1% EB injection and treatment with quercetin). The groups Querc and Querc+EB were treated once daily with quercetin (50mg/kg) diluted in 25% ethanol solution (1ml/kg) and the animals of the control and EB groups were treated once daily with 25% ethanol solution (1ml/kg). Two stages were observed: phase of demyelination (peak on day 7) and phase of remyelination (peak on day 21 post-injection). Behavioral tests (beam walking, foot fault and inclined plane test), acetylcholinesterase (AChE) activity and lipid peroxidation in pons, cerebellum, hippocampus, hypothalamus, striatum and cerebral cortex were measured. KEY FINDINGS: The quercetin promoted earlier locomotor recovery, suggesting that there was demyelination prevention or further remyelination velocity as well as it was able to prevent the inhibition of AChE activity and the increase of lipidic peroxidation, suggesting that this compound can protect cholinergic neurotransmission. SIGNIFICANCE: These results may contribute to a better understanding of the neuroprotective role of quercetin and the importance of an antioxidant diet in humans to provide benefits in neurodegenerative diseases such as MS.

NTPDase and 5'-nucleotidase activities from synaptosomes and platelets of rats exposed to cadmium and treated with N-acetylcysteine.

The purpose of the present investigation was to evaluate the hydrolysis of adenine nucleotides on synaptosomes and platelets obtained from rats exposed to cadmium (Cd) and treated with N-acetylcysteine (NAC). Rats received Cd (2 mg/kg) and NAC (150 mg/kg) by gavage every other day for 30 days. Animals were divided into four groups (n = 4-6): control/saline, NAC, Cd, and Cd/NAC. The results of this study demonstrated that NTPDase and 5'-nucleotidase activities were increased in the cerebral cortex synaptosomes of Cd-poisoned rats, and NAC co-treatment reversed these activities to the control levels. In relation to hippocampus synaptosomes, no differences on the NTPDase and 5'-nucleotidase activities of Cd-poisoned rats were observed and only the 5'-nucleotidase activity was increased by the administration of NAC per se. In platelets, Cd-intoxicated rats showed a decreased NTPDase activity and no difference in the 5'-nucleotidase activity; NAC co-treatment was inefficient in counteracting this undesirable effect. Our findings reveal that adenine nucleotide hydrolysis in synaptosomes and platelets of rats were altered after Cd exposure leading to a compensatory response in the central nervous system and acting as a modulator of the platelet activity. NAC was able to modulate the purinergic system which is interesting since the regulation of these enzymes could have potential therapeutic importance. Thus, our results reinforce the importance of the study of the ecto-nucleotidases pathway in poisoning conditions and highlight the possibility of using antioxidants such as NAC as adjuvant against toxicological conditions.

Hematological indices and activity of NTPDase and cholinesterase enzymes in rats exposed to cadmium and treated with N-acetylcysteine.

The present study aimed to investigate the influence of N-acetylcysteine (NAC) on cadmium (Cd) poisoning by evaluating Cd concentration in tissues, hematological indices as well as the activity of NTPDase, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes of rats exposed to Cd and co-treated with NAC. For this purpose, the rats received Cd (2 mg/kg) and NAC (150 mg/kg) by gavage every other day for 30 days. Animals were divided into four groups (n = 6-8): control/saline, NAC, Cd, and Cd/NAC. Cd exposure increased Cd concentration in plasma, spleen and thymus, and NAC co-treatment modulated this augment in both lymphoid organs. Cd exposure reduced red blood cell count, hemoglobin content and hematocrit value. Cd intoxication caused a decrease in total white blood cell count. NAC treatment per se caused an increase in lymphocyte and a decrease in neutrophil counts. On contrary, Cd exposure caused a decrease in lymphocyte and an increase in neutrophil and monocyte counts. NAC reversed or ameliorated the hematological impairments caused by Cd poisoning. There were no significant alterations in the NTPDase activity in lymphocytes of rats treated with Cd and/or NAC. Cd caused a decrease in the activities of lymphocyte AChE, whole blood AChE and serum BChE. However, NAC co-treatment was inefficient in counteracting the negative effect of Cd in the cholinesterase activities. The present investigation provides ex vivo evidence supporting the hypothesis that Cd induces immunotoxicity by interacting with the lymphoid organs, altering hematological parameters and inhibiting peripheral cholinesterase activity. Also, it highlights the possibility to use NAC as adjuvant against toxicological conditions.

Behavior and brain enzymatic changes after long-term intoxication with cadmium salt or contaminated potatoes.

This study investigated the cadmium (Cd) intoxication on cognitive, motor and anxiety performance of rats subjected to long-term exposure to diet with Cd salt or with Cd from contaminated potato tubers. Potato plantlets were micropropagated in MS medium and transplanted to plastic trays containing sand. Tubers were collected, planted in sand boxes and cultivated with 0 or 10 µM Cd and, after were oven-dried, powder processed and used for diet. Rats were divided into six groups and fed different diets for 5 months: control, potato, potato+Cd, 1, 5 or 25 mg/kg CdCl2. Cd exposure increased Cd concentration in brain regions. There was a significant decrease in the step-down latency in Cd-intoxicated rats and, elevated plus maze task revealed an anxiolytic effect in rats fed potato diet per se, and an anxiogenic effect in rats fed 25 mg/kg Cd. The brain structures of rats exposed to Cd salt or Cd from tubers showed an increased AChE activity, but Na+,K+-ATPase decreased in cortex, hypothalamus, and cerebellum. Therefore, we suggest an association between the long-term diet of potato tuber and a clear anxiolytic effect. Moreover, we observed an impaired cognition and enhanced anxiety-like behavior displayed by Cd-intoxicated rats coupled with a marked increase of brain Cd concentration, and increase and decrease of AChE and Na+,K+-ATPase activities, respectively.

Cholinesterase activities and biochemical determinations in patients with prostate cancer: influence of Gleason score, treatment and bone metastasis.

Prostate cancer (PCa) is the sixth most common type of cancer worldwide. Cholinesterase is well known as having non-cholinergic functions such as cellular proliferation and differentiation, suggesting a possible influence of cholinesterase in tumorogenesis. Thus, the aim of this study was to investigate the whole blood acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE) activities and some biochemical parameters in PCa patients. This study was performed in 66 PCa patients and 40 control subjects. AChE and BChE activities were determined in PCa patients and the influence of the Gleason score; bone metastasis and treatment in the enzyme activities were also verified. Furthermore, we also analyzed possible biochemical alterations in these patients. AChE and BChE activities decreased in PCa patients in relation to the control group and various biochemical changes were observed in these patients. Moreover, Gleason score, metastasis and treatment influenced cholinesterase activities and biochemical determinations. Our results suggest that cholinesterases activities and biochemical parameters are altered in PCa. These facts support the idea that the drop in the cholinesterase activity and the consequent increased amount of acetylcholine could lead to a cholinergic overstimulation and increase the cell proliferation in PCa.