Antidepressant-like effect of anacardic acid in mice via the L-arginine-nitric oxide-serotonergic system.

Depression, a multifactorial neuronal disorder with high morbidity/mortality, is associated with psychological, psychosocial, hereditary, and environmental etiologies, where reactive species exert pathophysiological functions. Anacardic acid (AA), a natural compound obtained from cashew nut liquid, has several pharmacological activities, including antioxidant and anticonvulsant. The aim of the present study was to evaluate the antidepressant-like effect of AA and the involvement of serotonergic, noradrenergic, and L-arginine-nitric oxide (NO) in tail suspension and forced swim tests and, more so, to investigate its antioxidant effect in Saccharomyces cerevisiae and in male Swiss mice (n = 8). In order to identify the antidepressant mechanisms, AA (10, 25, or 50 mg/kg, p.o.) was given 30 min before clonidine (2-adrenergic receptor agonist), L-arginine (NO precursor), propranolol (ß-adrenergic receptor antagonist), and several other agonists or antagonists used. On the other hand, clonidine, noradrenoreceptor, noradrenaline, and L-arginine were used to identify the antidepressant mechanisms. Results suggest that AA exerts antidepressant-like activity, especially at higher doses, possibly by inhibiting serotonin and 5HT-1A reuptake receptors and by inhibiting NO synthetase and guanylyl cyclase enzymes. Additionally, AA exhibited antioxidant effect in S. cerevisiae. This antioxidant capacity may be linked to its antidepressant-like effect but does not interact with α- and ß-adrenoceptor receptors. In conclusion, AA may be used as a promising agent to treat depression, especially which arises from oxidative stress.

Effect of Diets, Familial History, and Alternative Therapies on Genomic Instability of Breast Cancer Patients.

This study evaluates a correlation between family history, micronutrients intake, and alternative therapies with genetic instability, before and during breast cancer treatment. For this study, a total of 150 women were selected. Among those, 50 women were breast cancer patients on chemotherapy, while 50 breast cancer patients were on radiotherapy, and 50 were healthy females. All the participants signed the informed consent form and answered the public health questionnaire. Samples of buccal epithelial and peripheral blood cells were collected and analyzed through micronucleus and comet assays. The cells were evaluated for apoptosis and DNA damage. Results showed the association of patients' family history with an increase in toxicogenetic damage before and during cancer therapy. On the other hand, patients with late-onset cancer also presented genetic instability before and during therapy, along with those who did not take sufficient vegetables and alternative therapies. A positive correlation was observed between the genetic instability and alternative therapies, while inverse correlation was recorded with the vegetable consumption. Results clearly explain that the nutritional aspects and alternative therapies influence the genetic instability before and during cancer therapies especially in radiotherapy treated patients. Our data could be used for the monitoring therapies and management of breast cancer patients.

Toxicological evaluation of the biflavonoid, agathisflavone in albino Swiss mice.

Agathisflavone (AGF) is a biflavonoid with a number of important biological and pharmacological activities, such as antioxidant, antimicrobial, and neuroprotective effects. However, its toxicological effects have not been fully investigated. Accordingly, the aim of this study was to investigate the toxicological effects of AGF in mice. For this purpose, the median lethal dose 50% (LD50) was determined along with the anatomic and histopathological parameters (weight, alimentation, excretion, biochemical, and hematological) in fertile untouched female Swiss mice. Results suggest that during the treatment, no deaths were reported at 300 and 2000 mg/kg (n = 03/group, p.o.). Moreover, AGF did not cause significant change in the above mentioned parameters in test animals when compared with the control group (0.05% Tween 80 dissolved in 0.9% saline). Taken all together, this non-clinical toxicological study revealed that AGF has an LD50 larger than 2000 mg/kg and did not change significantly the hematological, biochemical, histopathological, behavioral, as well as physiological parameters in the female mice.

Anticonvulsant effect of anacardic acid in murine models: Putative role of GABAergic and antioxidant mechanisms.

Epilepsy is a neurological disease affecting people of all ages worldwide. Side effects of antiepileptic drugs and their association with oxidative stress stimulate the search for new drugs, which would be more affordable with fewer adverse effects. Accordingly, the aim of the present work is to evaluate the anticonvulsant effect of anacardic acid (AA), a natural compound extracted from cashew liquid (Anacardium occidentalis), in murine models, as well as its antioxidant actions in Saccharomyces cerevisiae. AA (>90% purity) was tested, in vivo, in male Swiss mice (25-30 g) with four convulsive models, (1) pentylenetetrazole, (2) pilocarpine, (3) electroshock, and (4) kainic acid, at doses of 25, 50, and 100 mg/kg, body weight (B.W.) Additionally, the effective dose, toxic dose, and protective index studies were also performed. Results revealed that AA exhibits anticonvulsive effects in models 1, 3, and 4, with a mean effective dose (ED50) of 39.64 (model 1) >100 mg/kg, B.W. (model 2), and 38.36 (model 3); furthermore, AA displays a protection index of 1.49 (model 1), <0.6 (model 2, and 1.54 (model 3). In addition, AA showed antioxidant activities in S. cerevisiae mutated for superoxide dismutases (SOD). In conclusion, these results show that AA exhibits significant anticonvulsant and antioxidant activities and may be used as a promising natural product for the treatment of epilepsy.

Pharmacological characterization of the cannabinoid receptor 2 agonist, ß-caryophyllene on seizure models in mice.

PURPOSE: Activation of CB1 receptors, produces anticonvulsant effect accompanied by memory disturbance both in animal seizure tests and in patients with epilepsy. Few reports considered the role of CB2 receptor on seizure susceptibility and cognitive functions. The aim of the present study was to explore the effect of a selective CB2 receptor agonist ß-caryophyllene (BCP) in models of seizures and cognition in mice. METHODS: Dose-dependent effects of BCP was studied in maximal electroshock seizure (MES) test, subcutaneous pentylenetetrazole (scPTZ) test and Morris water maze test. Phenytoin and diazepam were used as reference drugs in seizure tests. The effect of sub-chronic treatment with BCP for 7 days (50 and 100 mg kg-1) was assessed on status epilepticus (SE) induced by kainic acid (KA) model and oxidative stress through measurement of malondialdehyde (MDA) level in the hippocampus. The acute neurotoxicity was determined by a rotarod test. RESULTS: The BCP exerted a protection in the MES test at the lowest dose of 30 mg kg-1 at the 4-h interval tested comparable to that of the referent drug phenytoin. The CB2 agonist was ineffective in the scPTZ test. The BCP displayed no neurotoxicity in the rotarod test. The BCP decreased the seizure scores in the KA-induced SE, which effect correlated with a diminished lipid peroxidation. The CB2 agonist exerted a dose-dependent decrease of latency to cross the target area during the three days of testing in the Morris water maze test. CONCLUSION: Our results suggest that the CB2 receptor agonists might be clinically useful as an adjunct treatment against seizure spread and status epilepticus and concomitant oxidative stress, neurotoxicity and cognitive impairments.

Evaluation of toxic, cytotoxic and genotoxic effects of phytol and its nanoemulsion.

Phytol (PYT) is a diterpenoid having important biological activity. However, it is a water non-soluble compound. This study aims to prepare PYT nanoemulsion (PNE) and evaluation of toxic, cytotoxic and genotoxic activities of PYT and PNE. For this, the PNE was prepared by the phase inversion method. The cytotoxicity test was performed in Artemia salina, while toxicity, cytotoxicity and genotoxicity in Allium cepa at concentrations of 2, 4, 8 and 16 mM. Potassium dichromate and copper sulfate were used as positive controls for the tests of A. salina and A. cepa, respectively. In addition, an adaptation response was detected in A. cepa by using the comet assay. The results suggest that both PYT and PNE exhibited toxic and cytotoxic effects at 4-16 mM in either test system, while genotoxicity at 2-16 mM in A. cepa. PNE exhibited more toxic, cytotoxic and genotoxic effects at 8 and 16 mM than the PYT. However, both PYT and PNE at 2 and 4 mM decreased the index and frequency of damage in A. cepa after 48 and 72 h, suggesting a possible adaptation response or DNA damage preventing capacity. Nanoemulsified PYT (PNE) may readily cross the biological membranes with an increase in bioavailability and produce more toxic, cytotoxic and genotoxic effects in the used test systems.

Correlations between Risk Factors for Breast Cancer and Genetic Instability in Cancer Patients-A Clinical Perspective Study.

Molecular epidemiological studies have identified several risk factors linking to the genes and external factors in the pathogenesis of breast cancer. In this sense, genetic instability caused by DNA damage and DNA repair inefficiencies are important molecular events for the diagnosis and prognosis of therapies. Therefore, the objective of this study was to analyze correlation between sociocultural, occupational, and lifestyle risk factors with levels of genetic instability in non-neoplastic cells of breast cancer patients. Total 150 individuals were included in the study that included 50 breast cancer patients submitted to chemotherapy (QT), 50 breast cancer patients submitted to radiotherapy (RT), and 50 healthy women without any cancer. Cytogenetic biomarkers for apoptosis and DNA damage were evaluated in samples of buccal epithelial and peripheral blood cells through micronuclei and comet assay tests. Elder age patients (61-80 years) had higher levels of apoptosis (catriolysis by karyolysis) and DNA damage at the diagnosis (baseline damage) with increased cell damage during QT and especially during RT. We also reported the increased frequencies of cytogenetic biomarkers in patients who were exposed to ionizing radiation as well as for alcoholism and smoking. QT and RT induced high levels of fragmentation (karyorrhexis) and nuclear dissolution (karyolysis) and DNA damage. Correlations were observed between age and karyorrhexis at diagnosis; smoking and karyolysis during RT; and radiation and karyolysis during QT. These correlations indicate that risk factors may also influence the genetic instability in non-neoplastic cells caused to the patients during cancer therapies.

Phytol in a pharma-medico-stance.

This study aims to review phytol (PYT), through published articles, periodicals, magazines and patents, which were retrieved from the PM, SD, WS, SP; DII, WIPO, CIPO, USPTO and INPI databases. Among the 149 articles and 62 patents, 27.52% articles and 87.09% patients were found on the searched topic, PYT and its sources and synthesis and metabolism; then followed by 15.44% and 14.77% articles on PYT in cytotoxicity/cancer/mutagenicity/teratogenicity and PYT in neurological diseases, respectively. In the pharma-medico viewpoint, PYT and its derivatives have been evident to have antimicrobial, cytotoxic, antitumorous, antimutagenic, anti-teratogenic, antibiotic-chemotherapeutic, antidiabetic, lipid lowering, antispasmodic, anticonvulsant, antinociceptive, antioxidant, anti-inflammatory, anxiolytic, antidepressant, immunoadjuvancy, hair growth facilitator, hair fall defense and antidandruff activities. Otherwise, the important biometebolite of PYT is phytanic acid (PA). Evidence shows PA to have cytotoxic, anticancer, antidiabetic, lipid lowering and aniteratogenic activities. In addition, it may be considered as an important biomarker for some diseases such as Refsum's Disease (RD), Sjögren Larsson syndrome (SLS), rhizomelic chondrodysplasia punctata (RZCP), chronic polyneuropathy (CP), Zellweger's disease hyperpipecolic academia (ZDHA) and related diseases. Thus, phytol may be considered as a new drug candidate.