Jucimara Baldissarelli

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.

Iron and Oxidative Stress in Parkinson’s Disease: An Observational Study of Injury Biomarkers

Parkinsons disease (PD) is characterized by progressive motor impairment attributed to progressive loss of dopaminergic neurons in the substantia nigra (SN) pars compacta. In addition to an accumulation of iron, there is also an increased production of reactive oxygen/nitrogen species (ROS/RNS) and inflammatory markers. These observations suggest that iron dyshomeostasis may be playing a key role in neurodegeneration. However, the mechanisms underlying this metal-associated oxidative stress and neuronal damage have not been fully elucidated. To determine peripheral levels of iron, ferritin, and transferrin in PD patients and its possible relation with oxidative/nitrosative parameters, whilst attempting to identify a profile of peripheral biomarkers in this neurological condition. Forty PD patients and 46 controls were recruited to compare serum levels of iron, ferritin, transferrin, oxidative stress markers (superoxide dismutase (SOD), catalase (CAT), nitrosative stress marker (NOx), thiobarbituric acid reactive substances (TBARS), non-protein thiols (NPSH), advanced oxidation protein products (AOPP), ferric reducing ability of plasma (FRAP) and vitamin C) as well as inflammatory markers (NTPDases, ecto-5’-nucleotidase, adenosine deaminase (ADA), ischemic-modified albumin (IMA) and myeloperoxidase). Iron levels were lower in PD patients, whereas there was no difference in ferritin and transferrin. Oxidative stress (TBARS and AOPP) and inflammatory markers (NTPDases, IMA, and myeloperoxidase) were significantly higher in PD, while antioxidants FRAP, vitamin C, and non-protein thiols were significantly lower in PD. The enzymes SOD, CAT, and ecto-5’-nucleotidase were not different among the groups, although NOx and ADA levels were significantly higher in the controls. Our data corroborate the idea that ROS/RNS production and neuroinflammation may dysregulate iron homeostasis and collaborate to reduce the periphery levels of this ion, contributing to alterations observed in the pathophysiology of PD.

Effects of caffeic acid on behavioral parameters and on the activity of acetylcholinesterase in different tissues from adult rats

Acetylcholinesterase (AChE) is distributed throughout the body in both neuronal and non-neuronal tissues and plays an important role in the regulation of physiological events. Caffeic acid is a phenolic compound that has anti-inflammatory and neuroprotective properties. The aim of this study was to investigate in vitro and in vivo whether caffeic acid alters the AChE activity and behavioral parameters in rats. In the in vitro study, the concentrations of 0, 0.1, 0.5, 1.0, 1.5, and 2mM of caffeic acid were used. For the in vivo study, five groups were evaluated: group I (control); group II (canola oil), group III (10mg/kg of caffeic acid); group IV (50mg/kg of caffeic acid) and group V (100mg/kg of caffeic acid). Caffeic acid was diluted in canola oil and administered for 30 days. In vitro, the caffeic acid increased the AChE activity in the cerebral cortex, cerebellum, hypothalamus, whole blood, and lymphocytes at different concentrations. In muscle, this compound caused an inhibition in the AChE activity at concentrations of 0.5, 1.0, 1.5, and 2mM when compared to the control (P<0.05). In vivo, 50 and 100mg/kg of caffeic acid decreased the AChE activity in the cerebral cortex and striatum and increased the activity of this enzyme in the cerebellum, hippocampus, hypothalamus, pons, lymphocytes, and muscles when compared to the control group (P<0.05). The amount of 100mg/kg of caffeic acid improved the step-down latencies in the inhibitory avoidance. Our results demonstrated that caffeic acid improved memory and interfered with the cholinergic signaling. As a natural and promising compound caffeic acid should be considered potentially therapeutic in disorders that involve the cholinergic system.

Rosmarinic acid prevents lipid peroxidation and increase in acetylcholinesterase activity in brain of streptozotocin-induced diabetic rats.

We investigated the efficacy of rosmarinic acid (RA) in preventing lipid peroxidation and increased activity of acetylcholinesterase (AChE) in the brain of streptozotocin‐induced diabetic rats. The animals were divided into six groups (n = 8): control, ethanol, RA 10 mg/kg, diabetic, diabetic/ethanol and diabetic/RA 10 mg/kg. After 21 days of treatment with RA, the cerebral structures (striatum, cortex and hippocampus) were removed for experimental assays. The results demonstrated that the treatment with RA (10 mg/kg) significantly reduced the level of lipid peroxidation in hippocampus (28%), cortex (38%) and striatum (47%) of diabetic rats when compared with the control. In addition, it was found that hyperglycaemia caused significant increased in the activity of AChE in hippocampus (58%), cortex (46%) and striatum (30%) in comparison with the control. On the other hand, the treatment with RA reversed this effect to the level of control after 3 weeks. In conclusion, the present findings showed that treatment with RA prevents the lipid peroxidation and consequently the increase in AChE activity in diabetic rats, demonstrating that this compound can modulate cholinergic neurotransmission and prevent damage oxidative in brain in the diabetic state. Thus, we can suggest that RA could be a promising compound in the complementary therapy in diabetes. Copyright

Nitric oxide level, protein oxidation and antioxidant enzymes in rats infected by Trypanosoma evansi

The aim of this study was to evaluate the nitric oxide (NO()) level, protein oxidation and antioxidant enzymes in rats infected with Trypanosoma evansi and establish the association of NO() levels with the degree of parasitemia. Thirty-six male rats (Wistar) were divided into two groups with 18 animals each. Group A was not infected while Group B was intraperitoneally infected, receiving 7.5×10(6) trypomastigotes per animal. Each group was divided into three subgroups with 6 rats each and blood was collected during different periods post-infection (PI), as follows: day 5 (A(5) and B(5)), day 15 (A(15) and B(15)) and day 30 PI (A(30) and B(30)). Blood samples were collected by cardiac puncture to estimate the levels of nitrites/nitrates (NO(x)) and advanced oxidation protein products (AOPP) in serum, and superoxide dismutase (SOD) and catalase (CAT) activities in blood. On days 15 and 30 PI NO(x) and AOPP levels were increased in serum of rats infected. Rodents infected with T. evansi showed a significant increase in SOD (days 5 and 15 PI) and CAT (day 30 PI) activities. Based on the physiological role of NO(), we can conclude that its increased concentration is related to an inflammatory response against the parasite, once a redox imbalance was observed during infection.

Swimming Training Prevents Alterations in Acetylcholinesterase and Butyrylcholinesterase Activities in Hypertensive Rats

BACKGROUND Cholinergic enzyme activities are altered in hypertension, reflecting a low-grade inflammation. Regular physical exercise exerts anti-inflammatory effects and has been described as a coadjutant in the treatment of hypertension. In this study, we investigated the effect of 6 weeks of swimming training on cholinergic enzyme activities (acetylcholinesterase and butyrylcholinesterase) in Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. METHODS The rats were divided into 4 groups: control (n = 10), exercise (n = 10), L-NAME (n = 10), and exercise L-NAME (n = 10). The animals were trained 5 times per week in an adapted swimming system for 60 minutes with a gradual increase of the workload up to 5% of animals body weight. Enzyme activities were measured spectrophotometrically in lymphocytes, whole blood, and serum. RESULTS A significant rise in acetylcholinesterase activity was observed in lymphocytes and whole blood as well as in serum butyrylcholinesterase activity in the L-NAME group when compared with the other groups (P < 0.05), and the increase in cholinesterase activities was positively correlated with the rise in blood pressure (r = 0.5721, r = 0.6121, and r = 0.5811, respectively). Swimming training was efficient in preventing these alterations in the exercise L-NAME group, which displayed values similar to those of the control group. Exercise training demonstrated a significant hypotensive effect in hypertensive rats. CONCLUSIONS Exercise training was shown to prevent increased cholinesterase related to inflammatory processes in hypertensive rats, providing a new insight about protective exercise mechanisms to avoid hypertension-related inflammation.

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.

Berberine protects against memory impairment and anxiogenic-like behavior in rats submitted to sporadic Alzheimer’s-like dementia: Involvement of acetylcholinesterase and cell death

The present study aimed to investigate the effects of berberine (BRB) on spatial and learning memory, anxiety, acetylcholinesterase activity and cell death in an experimental model of intracerebroventricular streptozotocin (ICV-STZ) induced sporadic Alzheimers-like dementia. Sixty male Wistar rats were randomly divided into six groups: control (CTR), BRB 50mg/kg (BRB 50), BRB 100mg/kg (BRB 100), streptozotocin (STZ), streptozotocin plus BRB 50mg/kg (STZ+BRB 50), and streptozotocin plus BRB 100mg/kg (STZ+BRB 100). Rats were injected with ICV-STZ (3mg/kg) or saline, and daily oral BRB treatment began on day 4 for a period of 21days. Behavioral tests were carried out on day 17, and rats were euthanized on day 24. Cell death analysis and determination of acetylcholinesterase activity was performed on the cerebral cortex and hippocampus of the brain. Administration of BRB prevented the memory loss, anxiogenic behavior, increased acetylcholinesterase activity and cell death induced by ICV-STZ. This may be explained, in part, by a protective effect of BRB on ameliorating the progression of neurodegenerative diseases, including Alzheimers disease, and the results of this study provide a better understanding of the effect of BRB on the brain. Thus, BRB may act as a potential neuroprotective agent.

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

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

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

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