Involvement of the serotoninergic system in the anxiolytic action mechanism of a liposomal formulation containing nimodipine (NMD-Lipo).

In the search for anxiolytic drugs with fewer adverse effects, calcium blockers were proposed as a benzodiazepines (BZDs) alternative. In this context, the anxiolytic effect of nimodipine has been demonstrated. However, its low bioavailability and solubility could be improved by using nanostructured drug delivery systems such as liposomes. In this way, liposomal formulation containing nimodipine (NMD-Lipo) was developed. The NMD-lipo is a formulation capable of improving the kinetic characteristics of the drug, as well as the anxiolytic effect of nimodipine. In this work, the serotonergic system participation in the anxiolytic mechanism of the liposomal formulation containing nimodipine (NMD-Lipo) was investigated. A possible 5-HT1A receptor mediation on the NMD-Lipo anxiolytic effect was demonstrated by using WAY 100635 (5-HT1A receptor antagonist) since the antagonist reversed the NMD-Lipo anxiolytic effect in the light/dark test and elevated plus maze test. The results demonstrated that the NMD-Lipo administration had anxiolytic activity through 5-HT1A receptors without causing sedation or compromising the motor coordination of the tested animals.

Evaluation of the non-clinical toxicity of an antiparasitic agent: diminazene aceturate.

The diminazene aceturate (C14H15N7.2C4H7NO3) is a chemotherapeutic agent with more than six decades of use, however more studies regarding its toxicity still need to be performed. Thus, the present study determined the acute toxicity (14 days) of diminazene acetate (DIZE) in male and female swiss mice by changes in body mass, food consumption, biochemical and hematological parameters, locomotor activity and motor coordination. DIZE was administered at a single dose (1000 and 2000 mg/kg) orally. In addition, in vitro antioxidant capacity, hemolytic activity, toxicity in Artemia salina and in silico evaluation were also performed. The results obtained include several signs of toxicity (hypoactivity, loss of the straightening reflex and tachycardia), reduction of behavioral activity (locomotor activity and motor coordination) and significant changes (p < 0.05) in biochemical and hematological parameters. According to the in silico study, the DIZE can be classified based on the mean lethal dose (LD50) in category 4 (300 mg/kg < LD50 ≤ 2000 mg/kg, ProTox-II) or 3 (50 mg/kg < LD50 ≤ 300 mg/kg, AdmetSAR 1.0). Additionally, DIZE (30.3-969.9 nM) was not toxic to A. salina in the first 48 hours of treatment and was not cytotoxic to rat red blood cells after induced hemolysis. In vitro results indicated low antioxidant capacity against DPPH• and ABTS•+ radicals. Therefore, DIZE induces several adverse effects with influence on the central nervous system, changes in hematological and biochemical parameters and even mortality at the highest dose. However, absence of toxicity was observed in A. salina and rats red blood cells.

Neurochemical properties of neurospheres infusion in experimental-induced seizures.

Cell replacement through neural stem cells has been a promising alternative therapy for neurodegenerative diseases. It was evaluated the possible protect and/or prevent role of neurospheres in experimental models of epilepsy by the use of biomarkers of oxidative stress and histopathological analysis. After 1 h of the epileptic inductions by pilocarpine, pentylenotetrazole and picrotoxin, rats were infused with a suspension of 2 × 106 cells/0.25 mL, marked with Qtracker® 655, via caudal vein. In the control group epilepsy was not induced, but received the cell infusion under the same conditions of other groups. After 30 days, the rats were euthanized, and the removal of the brain was proceeded to later perform the assays oxidative stress and histopathology analysis. Thiobarbituric acid and nitrite levels were elevated in epileptic groups treated with neurospheres, and the levels of reduced glutathione, superoxide dismutase and catalase were reduced when compared to non-treated groups. The performance of oxidative enzymes from pilocarpine group treated with neurospheres showed slight increase. Histopathological evaluation observed distribution of neurospheres throughout the brain tissue, with viable cells and in process of differentiation in the pilocarpine group, but with differentiation and regeneration compromised in epilepsy by picrotoxin and pentylenetetrazole due to a microenvironment of oxidative stress. Neural stem cell therapy has a promising potential for protection in the pilocarpine epilepsy model, suggesting that the antioxidant system of neurospheres could reduce oxidative damage generated by seizure.

Determination of Parameters of Oxidative Stress in vitro Models of Neurodegenerative Diseases-A Review.

Oxidative stress is a major mechanism underlying the development of various neurodegenerative diseases (Alzheimer, Parkinson, Huntington and amyotrophic lateral sclerosis). Excessive formation of reactive oxygen species (ROS) and nitrogen (RNSs) can overburden the ability of the enzymatic antioxidant defense mechanisms (superoxide dismutase, catalase and glutathione reductase) and non-enzymatic (uric acid, ascorbic acid, α-tocopherol and reduced glutathione), causing the development of oxidative stress, and consequently, impairing the neuronal system cells by means of oxidative damage to a variety of important biological molecules such as lipids, DNA and proteins. Considering the importance of oxidative stress in neurodegenerative diseases, the present review aims to address the main parameters evaluated in in vitro studies on oxidative stress in different models of neurodegenerative diseases.The literary review was conducted through Pubmed, Science Direct, LILACS, Scielo and Google using following keywords: oxidative stress, neurodegenerative diseases and parameters of oxidative stress. We selected articles published between 2002 and 2017.The in vitro evaluation of the oxidative stress related parameters has provided a preliminary view about the pathogenesis of many neurodegenerative diseases (Alzheimer's, Parkinson's, Huntington's and Amyotrophic lateral sclerosis). In this way, it has demonstrated the mechanism of action of ROS/RNSs in these diseases by direct or indirect detection through several experimental procedures in vitro.

Phytochemistry Profile, Nutritional Properties and Pharmacological Activities of Mauritia flexuosa.

Mauritia flexuosa L. (Arecaceae) is a popular Brazilian fruit known as "buriti" and belonging to the category of functional foods. This work reviewed the phytochemistry profile, nutritional and pharmacological activities of M. flexuosa. The main bioactive compounds reported to buriti were carotenoids, tocopherols, ascorbic acid, phenolic compounds, fiber, phytosterols, and mono- and poly-unsaturated fatty acids. These compounds were mainly related to antioxidant, hypolipemiant, photoprotector, antiaggregant, antithrombotic, anti-inflammatory, hypoglycemiant, antimicrobial, and antitumor activities. Furthermore, some compounds present in buriti fruit and its properties were tested in vitro and in vivo and showed biotechnology applications, especially for extraction of fiber, polysaccharides, pigments, antioxidants, and oil. Howerer, the buriti fruit shows great relevance to the development of new products in food, pharmaceutical and chemical industry, this fruit is still underexploited and it has need to expand its production chain and processing to encourage their consumption and utilization.

Diminazene aceturate--An antiparasitic drug of antiquity: Advances in pharmacology & therapeutics.

Diminazene aceturate (C14H15N7.2C4H7NO3) is an aromatic diamidine that was developed more than six decades ago and has been marketed until today for the control of trypanosomiasis. In recent years, however, this trypanocidal compound has been extensively studied with respect to its therapeutic potential and has consequently attracted much interest for the development of further research. The objective of this study was to conduct a systematic review on diminazene aceturate regarding its pharmacological properties. In this way, databases were searched for articles (ScienceDirect, Scopus, PubMed, Web of Science and SciFinder) and patents (INPI, USPTO, WIPO, DPMA, SIPO, DERWENT, CIPO and EPO). For the development of this review, 115 articles and 22 patents were selected and analyzed. It was thus possible to highlight several researches that have investigated alternatives in order to improve success in the treatment of animal trypanosomiasis, by using new drugs in associations with diminazene aceturate, as well as looking for new pharmacological applications for this compound, such as leishmanicidal, amebicidal, anti-pneumocystis, anti-rheumatoid arthritis, antihypertensive agent, and mainly as an activator of angiotensin-converting enzyme 2. Another pharmacological property still little studied is the inhibition of acid-sensitive ion channels (ASIC1a, ASIC1b, ASIC2a and ASIC3), which are related to the development of various diseases. Collectively, these studies conducted by several research groups extend the use of diminazene aceturate beyond the antitrypanosomal activity and suggest promising new applications.