Márcia Fernanda Correia Jardim Paz

Therapeutic Potential of Essential Oils Focusing on Diterpenes.

Among all plant derivates, essential oils (EOs) have gained the attention of many scientists. Diterpenes, a family of components present in some EO, are becoming a milestone in the EOs world. The goal of this review is to describe a scenario of diterpenes taking into health‐consumption deportment. Previous studies revealed that diterpenes have antioxidant, antimicrobial, antiviral, antiprotozoal, cytotoxic, anticancer, antigenotoxic, antimutagenic, chemopreventive, antiinflammatory, antinociceptive, immunostimulatory, organoprotective, antidiabetic, lipid‐lowering, antiallergic, antiplatelet, antithrombotic, and antitoxin activities. In conclusion, diterpenes may be an immense featuring concern in pharmaceutical consumption from a drug discovery point of view. Copyright

Diterpenes: Advances in Neurobiological Drug Research

A significant number of studies have been performed with diterpene effect on the brain. Our study aims to make a systematic revision on them. The initial purpose of this review was to screen diterpenes with neurological activity, in particular those that have already been studied and published in different journals (databases until August 2015). The second purpose was to make an action‐wise discussion as results viewed on them by taking into drug discovery and development account. Diterpenes considered in this review were selected on the basis of updated information on them and having sufficient information on their screenings. We identified several examples of diterpenes having an interest in further study. We have included the possible sources of them as observed in evidence, their known molecular neurobiological mechanisms, and the active constituents responsible for such activities with the doses and test systems. Results suggest diterpenes to have neurobiological activities like neuro‐protection, anti‐epileptic, anxiolytic, anti‐Alzheimers disease, anti‐Parkinsons disease, anti‐cerebral ischemia, anti‐neuropathic pain, anti‐neuro‐inflammatory, and many more. In conclusion, diterpenes may be the prominent candidates in neurobiological drug research. Copyright

A Possible Phytol-cytoprotective Trait through Reactive Species-Induced Oxidative Stress Ebbing Pathway

This study aims at investigating a possible pathway of cytotoxicological status of the diterpenoid essential oil, phytol (PYL). For this brine shrimp lethality bioassay (BSLB) and hemolysis (HL) test systems were selected. In the BSLB, PYL either alone or co-treated with ethylenediaminetetraacetic acid (EDTA), potassium di-chromate (K2Cr2O7; KD), copper sulphate (CuSO4.5H2O; CS) and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox, TRO) as membrane lyser, strong oxidizer, oxidizer-cytogenotoxicant and antioxidative-cell-protestant, respectively. The HL was carried out in rat erythrocytes (RBCs) taking TRO as a standard. In addition, to view a time-dependent cytotoxic activity of PYL, the mortality of the shrimps was counted at 24 and 48 h. Results suggest PYL is non-cytotoxic at low (40-160 µM) but toxic at high concentration (2-8 mM) to the shrimps and RBCs. An increased cytotoxicity was observed for 24 h to 48 h in brine shrimps. In both cases groups co-treated with cytotoxicants/protestant suggest that PYL is cytoprotective in the presence of oxidizer. The cytoprotectivityof PYL may be connected to its antioxidant potential and cytotoxicity for antioxidant-mediated pro-oxidative effects. In conclusion, PYL is cytoprotective at low concentration but toxic at high, activities found, however, may be linked to the radical scavenging pathway

Serum Oxidative Stress Markers and Genotoxic Profile Induced by Chemotherapy in Patients with Breast Cancer: A Pilot Study

The aim of this study was to evaluate the oxidative parameters of erythrocytes and genotoxicity in leukocytes of patients with breast cancer. Oxidative parameters were detected by spectrophotometry and genotoxic damage by single cell gel electrophoresis. Twenty-eight women with breast cancer were monitored before chemotherapy and after the second and fourth cycles of therapy with cyclophosphamide and doxorubicin. After the fourth cycle, increases (P < 0.05) in the reactive substances to thiobarbituric acid levels, nitrite content, and superoxide dismutase activity and high rates of DNA damage in leukocytes were observed when compared with healthy women group and baseline levels. Similarly, after the second cycle, the same parameters were increased (P < 0.05) when compared with baseline levels. Increase in catalase activity was detected only after the fourth cycle and reduced glutathione levels and glutathione peroxidase activity were decreased in all cycles when compared with healthy women, as well as after the second and fourth chemotherapy cycles compared to baseline (P < 0.05). Patients with breast cancer presented an indicative of oxidative stress before, during, and after chemotherapy, as well as increased genotoxic damage in all stages of treatment, demonstrating the clinical applicability of this investigation.

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.

A comprehensive review on biological properties of citrinin

Citrinin (CIT) is a mycotoxin which causes contamination in the food and is associated with different toxic effects. A web search on CIT has been conducted covering the timespan since 1946. The accumulated data indicate that CIT is produced by several fungal strains belonging to Penicillium, Aspergillus and Monascus genera, and is usually found together with another nephrotoxic mycotoxin, ochratoxin A. Although, it is evident that CIT exposure can exert toxic effects on the heart, liver, kidney, as well as reproductive system, the mechanism of CIT-induced toxicity remains largely elusive. It is still controversial what are the genotoxic and mutagenic effects of CIT. Until now, its toxic effect has been linked to the CIT-mediated oxidative stress and mitochondrial dysfunction in biological systems. However, the toxicity strongly depends on its concentration, route, frequency and time of exposure, as well as from the used test systems. Besides the toxic effects, CIT is also reported to possess a broad spectrum of bioactivities, including antibacterial, antifungal, and potential anticancer and neuro-protective effects in vitro. This systematic review presents the current state of CIT research with emphasis on its bioactivity profile.

Genotoxicity and DNA Repair Indicative in Blood Cells after Occupational Exposure to Ionizing Radiation

Occupational exposure to ionizing radiation (IR) can damage DNA. The study evaluated the genotoxic profile and repair indicatives of DNA from peripheral blood lymphocytes of health workers exposed occupationally to IR by adopting comet assay. Biomonitoring was done with ninety individuals; among them 45 were health professionals and the rests were non-professionals. Blood samples were collected after 48 h (2 d; non-exposed) and 168 h (7 d; exposed). The 7 d IR exposed group significantly increased in the rates and frequency of damage, while 2 d unexposed group exhibited more than 20% of DNA repair as compared to the respective control groups. The DNA damage was observed in more significant to the younger workers (18-27 y). However, the hematological abnormalities were not observed, despite of their positive correlation in genotoxic profile. Significant and positive correlations were observed in relation to the used medicaments, low consumption of vegetables as well as the type and place of work. In conclusion, biomarkers involved in comet assay can be applied in biomonitoring of genetic instability, including IR induced phenomena.

Genotoxicidade e nefrotoxicidade da Morinda citrifolia em estudos pré-clínicos: riscos à saúde pública

O estudo tem como objetivo investigar os possiveis efeitos genotoxicos e nefrotoxicos do fruto do Noni em Rattus norvegicus . Trata-se de um estudo experimental com 50 Rattus norvegicus , com massa corporal de 200 a 250g, distribuidos em grupos experimentais (n=10); 5 machos e 5 femeas: controle negativo (agua destilada), controle positivo (25 mg/kg de ciclofosfamida, i.p.) e 3 doses de extrato do fruto Noni (10; 5 e 2,5 mg/kg), por 14 dias de tratamento. No 17o dia, os animais foram sacrificados para retirada de amostras de sangue, para dosagem serica de ureia e creatinina; e amostras de tecido renal, para avaliacao de genotoxicidade com o Teste Cometa. Danos significativos ao DNA foram observados em celulas renais, pelo aumento de indice e frequencia de danos em ambos os generos nas duas maiores doses de Noni. Entretanto, nao houve significativo aumento do nivel serico de ureia e creatinina- biomarcadores de injuria renal. Dessa forma, o extrato do fruto do Noni tem potencial genotoxico de forma dose-dependente, sugerindo riscos potenciais para a saude humana e a necessidade de se estabelecer doses seguras.

Cytogenotoxicological defense of retinyl palmitate in the front damage of antineoplastics

Cancer, the multifactorial pathology and to date is the most lethal causes of death in the world. Cyclophosphamide (CPA) and doxorubicin (DOX) are the individually or combindly used two anticancer drugs. The antineoplastic drugs-mediated genetic instability can be overcome by using antioxidants. The study evaluated the cytogenotoxic modulatory potentials of retinyl palmitate (RP) caused by CPA and DOX in Swiss mice. For this, adult Mus musculus of either sex were divided equally regarding to the gender. Toxicogenetic effects were induced by the intraperitoneal (i.p.) administration of the CPA (20mg/kg) and/or DOX (2mg/kg), following to test for comet assay and micronucleus test in bone marrow cells after 48h (DOX) and 7h (CPA) of the administration of RP (100 IU/kg). Both CPA and DOX significantly (p<0.05) increased with the index and frequency of damages, clastogenic and/or aneugenic effects with the augmenting of micronuclei, demonstrating the cytotoxicity interference on the ratio of normochromatic to polychromatic erythrocytes and bone marrow cells of mice, that were found to reduce in RP treatment groups. In conclusion, RP has a modulatory effect on CPA and DOX-mediated cytogenotoxic events. The findings may be a good indication to manage the antioneoplastic drug-induced stress mediated detrimental effects by using RP, especially as a side effect minimizer.

Anxiolytic effect of anacardic acids from cashew (Anacardium occidentale) nut shell in mice

Antianxiety drugs currently in use are associated with a number of serious side effects. Present study was designed to evaluate the efficacy of anacardic acids (AAs) isolated from cashew nut (Anacardium occidentale L.) shell liquid (CNSL) to treat anxiety as well as its role in oxidative stress in mice model. Anxiolytic effect of AA was evaluated using rota‐rod and a set of behavioral tests in male Swiss albino mice at the doses of 10, 25, and 50 mg/kg. Flumazenil was used to evaluate the possible involvement of GABAergic system in the mechanism of action of AA. The effect of AA on oxidative stress in mice was evaluated by determining the concentration of malondialdehyde (MDA), reduced glutathione, and catalase (CAT) activity. The detection of DNA damage of the treated animals was performed using alkaline comet test in the hippocampus and frontal cortex of the animals. The results demonstrated that AA did not produce myorelaxant and sedative effects, nor did it cause a decrease in locomotor activity. The anxiolytic effect of AA was well‐evident in all tests, especially at higher dose levels (25 and 50 mg/mg). Flumazenil reversed the anxiolytic effect of AA at all doses. In addition, AA reduced oxidative stress by decreasing the concentration of MDA and increasing the levels of reduced glutathione (GSH) and CAT activity. Statistical analysis by Pearsons correlation indicated a positive correlation between anxiolytic effect of AA to its antioxidant and lipid peroxidation inhibitory activity. Furthermore, increased CAT activity and GSH concentrations in the hippocampus and frontal cortex of mice was also complementary to the reduced genotoxic damage observed in the study. In comet assay, AA did not increase in DNA damage. In conclusion, the results supported that AA possesses GABAA receptor mediated anxiolytic activity with the lack of myorelaxation and genotoxicity.