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.

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.

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.

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.