Is there still a place for involutional melancholia nowadays?

Ethnopharmacological relevance: Rubus niveus Thunb. plant belongs to Rosaceae family and have been used traditionally to treat wounds, burns, inflammation, dysentery, diarrhea and for curing excessive bleeding during menstrual cycle. The present study was undertaken to investigate the in vivo genotoxicity of Rubus niveus aerial parts extract and its possible chemoprotection on doxorubicin (DXR)-induced DNA damage. In parallel, the main phytochemicals constituents in the extract were determined.Materials and methods: The animals were exposed to the extract for 24 and 48 h, and the doses selected were 500, 1000 and 2000 mg/kg b.w. administered by gavage alone or prior to DXR (30 mg/kg b.w.) administered by intraperitoneal injection. The endpoints analyzed were DNA damage in bone marrow and peripheral blood cells assessed by the alkaline alkaline (pH > 13) comet assay and bone marrow micronucleus test.Results and conclusion: The results of chemical analysis of the extract showed the presence of tormentic acid, stigmasterol, quercitinglucoronide (miquelianin) and niga-ichigoside F1 as main compounds. Both cytogenetic endpoints analyzed showed that there were no statistically significant differences (p > 0.05) between the negative control and the treated groups with the two higher doses of Rubus niveus extract alone, demonstrating absence of genotoxic and mutagenic effects. Aneugenic/clastogenic effect was observed only at 2000 mg/kg dose. On the other hand, in the both assays and all tested doses were observed a significant reduction of DNA damage and chromosomal aberrations in all groups co-treated with DXR and extract compared to those which received only DXR. These results indicate that Rubus niveus aerial parts extract did not revealed any genotoxic effect, but presented some aneugenic/clastogenic effect at higher dose; and suggest that it could be a potential adjuvant against development of second malignant neoplasms caused by the cancer chemotherapic DXR. (C) 2015 Elsevier Ireland Ltd. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Assessment of the potential clastogenic/aneugenic risk of Casearia sylvestris extract using in vivo assays

Casearia sylvestris (Flacourtiaceae) is a plant which grows in wild and has been widely used in folk medicine. In this study, clastogenic/aneugenic properties of Casearia sylvestris crude ethanolic extract were evaluated using in vivo chromosomal aberrations (CAs) and micronucleus (MN) assays in rodents. The animals were treated by gavage with 3 concentrations of the extract: 150, 300 and 500 mg/kg body weight. Bone marrow cells from Wistar rats were collected 24 h after having been submitted to the MN and CAs test. Peripheral blood cells from Swiss mice were collected 48 and 72 h after having been submitted to the MN test. The results show that C. sylvestris extract does not induce a significant increase in mean values for micronucleated polychromatic erythrocytes (MNPCE) in Swiss mice and Wistar rats, or CAs in rat bone marrow cells, at the 3 tested doses, indicating that the extract showed no clastogenic/aneugenic effects on chromosomes of the rodent cells tested. © 2007 The Japan Mendel Society

Optoacoustic Imaging Offers New Insights into In Vivo Human Skin Vascular Physiology

Functional imaging with new photoacoustic tomography (PAT) offers improved spatial and temporal resolution quality in in vivo human skin vascular assessments. In the present study, we followed a suprasystolic reactive hyperemia (RH) maneuver with a multi-spectral optoacoustic tomography (MSOT) system. A convenience sample of ten participants, both sexes, mean age of 35.8 ± 13.3 years old, was selected. All procedures were in accordance with the principles of good clinical practice and approved by the institutional ethics committee. Images were obtained at baseline (resting), during occlusion, and immediately after pressure release. Observations of the RH by PAT identified superficial and deeper vascular structures parallel to the skin surface as part of the human skin vascular plexus. Furthermore, PAT revealed that the suprasystolic occlusion impacts both plexus differently, practically obliterating the superficial smaller vessels and evoking stasis at the deeper, larger structures in real-time (live) conditions. This dual effect of RH on the skin plexus has not been explored and is not considered in clinical settings. Thus, RH seems to represent much more than the local microvascular reperfusion as typically described, and PAT offers a vast potential for vascular clinical and preclinical research

First in vivo evaluation of the mutagenic effect of Brazilian green propolis by comet assay and micronucleus test

Propolis is a hive product containing chiefly beeswax and plant-derived substances such as resin and volatile compounds. Propolis has been used in various parts of the world as an antiseptic and wound healer since ancient times, and interest in the product has recently increased. Considering the lack of data concerning the in vivo mutagenicity of green propolis, the capacity of this natural product to cause damage to the DNA was evaluated, using the alkaline single-cell gel electrophoresis (SCGE) and micronucleus test, in the peripheral blood cells of mice. The doses tested by gavage were 1000, 1500 and 2000 mg/kg. Micronucleus and SCGE assays showed that green propolis caused an increase in the damage to DNA in the peripheral blood cells of mice. The polychromatic: normochromatic erythrocytes ratio was not statistically different from the negative control. Considering the doses and the results obtained in this study, the acute consumption of green propolis produced some mutagenic effects on the blood cells of mice. (C) 2008 Elsevier Ltd. All rights reserved

In vivo genotoxicity assessment of nerolidol

Nerolidol is a sesquiterpenoid component of essential oil used as a flavor and aroma enhancer. It has also been studied as a topical skin penetration enhancer, and has inhibitory activities against S. aureus and E. coli, among other activities. The objective of this study was to evaluate the ability of a single nerolidol treatment to induce DNA damage in peripheral blood and liver cells of mice and micronuclei in polychromatic erythrocytes of bone marrow cells of the same animals. In the dose range-finding assays, the maximum tolerated dose was higher than 2000 mg kg(-1). The doses used in the experiments were 250, 500 and 2000 mg kg(-1), administered by gavage in a single dose. Peripheral blood cells were collected 4 and 24 h after the treatments and liver cells 24 h after. At least 100 nucleoids per cell type/animal were analyzed to determine the DNA damage scores and 2000 PCEs per animal for micronuclei in PCEs. The positive control was N-nitroso-N-ethylurea 50 mg kg(-1). Cytotoxicity was assessed by scoring 200 consecutive total polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE: NCE ratio). The results showed that nerolidol induced weak levels of dose-related DNA damage in both types of cells analyzed, and enhanced the average number of micronucleated cells in the two high doses tested. The PCE: NCE ratio showed no cytotoxicity for the three doses of the compound. The data obtained support the view that nerolidol induces clastogenicity and very weak genotoxicity in the mouse cells tested. Copyright (C) 2010 John Wiley & Sons, Ltd.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Epididymis-specific pathologic disorders in rats exposed to gossypol from weaning through puberty

Previous work in our laboratory revealed that the pubertal period of reproductive development in the male rat was particularly vulnerable to gossypol exposure, with a higher frequency of round structures in the lumen of the cauda epididymidis in the treated rats. Herein, we utilized hemicastration and electron microscopy to confirm that the epididymis is a definitive target of gossypol. Although exposure to gossypol from weaning through puberty caused a significant decrease in daily sperm production, as well as in the concentration of sperm in the epididymis, serum testosterone levels and reproductive organ weights were not altered. In gossypol treated rats, sperm morphology was compromised severely, but the epithelium in testis and epididymis appeared morphologically normal. Ultrastructural examination revealed that round structures, present only in gossypol exposed males, represented: (1) principal cells exfoliated from the epididymal epithelium; (2) epididymal epithelial cell cytoplasm containing degenerating sperm; and (3) degenerating epithelial cells, consisting of vesicles and particles of different sizes, forms and densities. Taken together, the data confirm that gossypol targets the epididymis, disturbing both the structure and function of this organ, and presumably disrupts sperm maturation

Evaluation of the genotoxic and antigenotoxic potential of Brassica oleracea L. var. acephala D.C. in different cells of mice

Ethnopharmacological relevance: Brassica oleracea L var. acephala D.C. has been extensively used in Brazilian traditional medicine to treat gastric ulcer.Aim of the study: This study was conducted to evaluate the in vivo genotoxic and/or antigenotoxic potential of a Brassica oleraceae hydroalcoholic extract obtained from the leaves, in different cells of mice.Materials and methods: Analyses were performed using the comet assay, on leukocytes (collected 4 and 24 h after treatment), liver, brain, bone marrow and testicular cells (collected 24 h after treatment), and using the micronucleus test (MN) in bone marrow cells. Eight groups of albino Swiss mice were treated (N=6): control (C), positive control (doxorubicin 80 mg/kg (DXR)), and six experimental groups, which received 500, 1000 and 2000 mg/kg of Brassica oleraceae extract alone by gavage, while a further three groups received the same doses plus DXR (80 mg/kg). We calculated the damage scores, and their averages were compared by ANOVA followed by the Tukey test for multiple comparisons.Results: The results demonstrated that none of the tested doses of Brassica oleraceae extract showed genotoxic effects by the comet assay, or clastogenic effects by the MN test. on the other hand, for all cells evaluated, the three tested doses of the Brassica extract promoted inhibition of DNA damage induced by DXR.Conclusions: Under our experimental conditions, Brassica oleraceae leaf extract showed no genotoxic or clastogenic effects in different cells of mice. However, it did show a significant decrease in DNA damage induced by doxorubicin. It is suggested that the antigenotoxic properties of this extract may be of great pharmacological importance, and may be beneficial for cancer prevention. (C) 2012 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Analyse der auditiven Mismatch-Negativität mit einem spatio-temporalen Quellenmodell

Ethnopharmacological relevance: Garcinia achachairu Rusby (Clusiaceae) is popularly known as "achachairu", and is used in Bolivian folk medicine for its healing, digestive, and laxative properties, and in the treatment of gastritis, rheumatism and inflammation. Despite its widespread therapeutic use, there is a lack of data regarding its in vivo genotoxic effects. Therefore, in this study, we used the comet assay and the micronucleus test, respectively, to evaluate the possible genotoxic and clastogenic effects of Garcinia achachairu seed extract (GAE) on different cells of mice.Material and methods: The GAE was administered by oral gavage at doses of 500, 1000 and 2000 mg/kg. For the analysis, the comet assay was performed on the leukocytes (collected 4 and 24 h after treatment), liver, bone marrow and testicular cells (collected 24 h after treatment), and the micronucleus test (MN) on bone marrow cells. Cytotoxicity was assessed by scoring 200 consecutive polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE/NCE ratio).Results and conclusion: The results showed that GAE did not induce significant DNA damage in leukocytes (4 h and 24 h samples), liver, bone marrow and testicular cells (24 h samples). GAE also did not show any significant increase in micronucleated polychromatic erythrocytes (MNPCEs) at the three tested doses. The PCE/NCE ratio indicated no cytotoxicity. Under our experimental conditions, the data obtained suggest that a single oral administration of G. achachairu extract does not cause genotoxicity and clastogenicity in different cells of mice. (C) 2012 Elsevier B.V. All rights reserved.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

The PPARγ-dependent effect of flavonoid luteolin against damage induced by the chemotherapeutic irinotecan in human intestinal cells.

International audienceIrinotecan (CPT-11) is one of the main agents used to treat colorectal cancer; unfortunately, it is associated with increased intestinal mucositis developing. Luteolin has been shown to prevent damage induced by this chemotherapeutic in mice; thus, in this research, we have investigated luteolin's action mechanism in human intestinal epithelial cells. The potential of luteolin in reducing inflammation and oxidative stress induced by irinotecan in Caco-2 cells was evaluated by PCR through mRNA expression of inflammatory and oxidative genes and by ELISA at the protein level. To assess whether luteolin's ability to control irinotecan-induced damage occurs in a PPARγ dependent manner, experiments were performed on PPARγ downregulated cells. Irinotecan downregulated PPARγ expression and upregulated inflammatory and oxidative genes, while luteolin upregulated PPARγ, HO-1, SOD and decreased expression of IL-1β and iNOS. Interestingly, when the cells were co-stimulated with luteolin and irinotecan, the flavonoid reversed the inflammation and oxidative imbalance evoked by the chemotherapeutic. However, when these experiments were performed in cells downregulated for PPARγ, luteolin lost the capacity to increase PPARγ and reverse the effect of irinotecan in all tested genes, except by IL-1β. The present study showed that the protective effect of luteolin against irinotecan is PPARγ dependent

Dragon's blood Croton palanostigma induces genotoxic effects in mice

Ethnopharmacological relevance: Dragon's blood is a dark-red sap produced by species from the genus Croton (Euphorbiaceae), which has been used as a famous traditional medicine since ancient times in many countries, with scarce data about its safe use in humans. in this research, we studied genotoxicity and clastogenicity of Croton palanostigma sap using the comet assay and micronucleus test in cells of mice submitted to acute treatment.Material and methods: HPLC analysis was performed to identify the main components of the sap. the sap was administered by oral gavage at doses of 300 mg/kg, 1000 mg/kg and 2000 mg/kg. for the analysis, the comet assay was performed on the leukocytes and liver cells collected 24 h after treatment, and the micronucleus test (MN) on bone marrow cells. Cytotoxicity was assessed by scoring 200 consecutive polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE/NCE ratio).Results and conclusion: the alkaloid taspine was the main compound indentified in the crude sap of Croton palanostigma. the results of the genotoxicity assessment show that all sap doses tested produced genotoxic effects in leukocytes and liver cells and also produced clastogenic/aneugenic effects in bone marrow cells of mice at the two higher doses tested. the PCE/NCE ratio indicated no cytotoxicity. the data obtained suggest caution in the use of Croton palanostigma sap by humans considering its risk of carcinogenesis. (C) 2013 Elsevier Ireland Ltd. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Estadual Paulista UNESP, Dept Fonoaudiol, Fac Filosofia & Ciencias, BR-17525900 Marilia, SP, BrazilUniv Vale Itajai UNIVALI, Nucleo Invest Quim Farmaceut NIQFAR, Itajai, SC, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Ciencias Exatas & Terra, Diadema, SP, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Ciencias Exatas & Terra, Diadema, SP, BrazilWeb of Scienc