RESUMEN
BACKGROUND: Exposure to vinylcyclohexene (VCH) and methylmercury (MeHg+) can induce oxidative stress and gene modulation. Several studies have been evaluating the effects of VCH and MeHg+, but little is known about interactive effects between them. This work aimed to assess the exposure and co-exposure effects of MeHg+ and VCH on oxidative stress and gene modulation in Drosophila melanogaster. METHODS: Reactive species production, glutathione S-transferase (GST) and acetylcholinesterase (AChE) activities were evaluated after exposure and co-exposure to VCH (1 mM) and MeHg+ (0.2 mM) for one or three days in the head and body (thorax and abdomen) of flies. The expression of genes related to redox state and inflammatory response was evaluated after exposure and co-exposure to VCH and MeHg+ for three days. RESULTS: Survival decreased only in flies co-exposed to VCH and MeHg+ for three days. All treatments increased total reactive species production after one day of exposure. However, no significant changes were observed in the head after three days of exposure. One day of exposure to VCH caused an increase in the head GST activity, whereas MeHg+ induced an increase after three days of exposure. Regarding the body, all treatments increased GST activity after one day of exposure, but only the flies exposed to MeHg+ presented an increase in GST activity after three days of exposure. Treatments did not alter AChE activity in the head. As for gene expression, there was a significant increase in the Relish transcription factor gene in the flies' body, but Nrf2, Keap1, Jafrac1, TrxR1, and NF-κß were not altered. CONCLUSION: The results suggest that exposure to VCH and MeHg+ induce oxidative stress and activation of an inflammatory response in fruit flies.
Asunto(s)
Ciclohexenos/toxicidad , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/efectos de los fármacos , Expresión Génica/efectos de los fármacos , Compuestos de Metilmercurio/toxicidad , Acetilcolinesterasa/genética , Acetilcolinesterasa/metabolismo , Animales , Ciclohexenos/administración & dosificación , Relación Dosis-Respuesta a Droga , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Sinergismo Farmacológico , Glutatión Transferasa/genética , Glutatión Transferasa/metabolismo , Compuestos de Metilmercurio/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/genéticaRESUMEN
Vinylcyclohexene (VCH) is an environmental contaminant well known for its ovotoxicant effects in several organisms. However, the mechanisms underlying the toxicity of VCH as well as its harmful effects toward other organs are until unclear. In this work, we assess some endpoint signals of toxicity induced by volatilized VCH exposure using nymphs of the lobster cockroach Nauphoeta cinerea. Nymphs were exposed to VCH via inhalation for 70 days. The levels of volatilized VCH were quantified by headspace gas chromatography and the concentration varied between 3.41 and 7.03â¯nmol/µl. VCH inhalation caused a reduction of 35% in the survival rate of the exposed animals. Nymphs exposed to volatilized VCH for 35 and 70 days had a reduction in the body weight gain of 1.8- and 2.6-fold, respectively with a reduction in dissected head, fat body, and maturing reproductive organs. The exposure did not change water consumption, excepting on the 20th day (with a 3-fold change) and decreased the food intake significantly. Regarding biochemical markers, we found that the activity of GST from the dissected organs was increased by volatilized VCH after both 35 and 70 days of exposure. The fat body presented the most prominent GST activity especially after 35 days of exposure with 1.6-fold higher than the control group. Exposure also caused an increase in RS levels in the fat body of 1.35-fold and 1.47-fold after 35 and 70 days, respectively and did not affect the activity of the AChE from the head. Our findings support the harmful impact of volatilized VCH inhalation, highlighting the cockroach N.cinerea as a valuable insect model to investigate environmental toxicants.
Asunto(s)
Cucarachas/efectos de los fármacos , Ciclohexenos/toxicidad , Ninfa/efectos de los fármacos , Administración por Inhalación , Animales , Cucarachas/enzimología , Cuerpo Adiposo/efectos de los fármacos , Cuerpo Adiposo/enzimología , Glutatión Transferasa/metabolismo , Ninfa/enzimología , VolatilizaciónRESUMEN
The use in folk medicine of Baccharis trimera and recent studies on DNA damage by oxidative stress mechanisms have motivated this study. We investigated the biotoxicological effects of trimeroside from this plant. Aqueous extract from aerial parts of B. trimera was fractioned by flash chromatography for further isolation by thin-layer chromatography. The novel nor-monoterpene glycoside, trimeroside, and three flavonoids, cirsimaritin, luteolin and quercetin, were isolated. The genotoxic and mutagenic potential of trimeroside was determined by Salmonella/microsome (TA98 and TA100), comet assay, and cytokinesis-block micronucleus cytome assay (CBMN-cyt) in HepG2 cells. We also screened trimeroside into different human tumoral cell lines by sulforhodamine B (SRB) assay. Mutagenicity was detected in TA100 strain with metabolic activation. Genotoxic effects were not observed in HepG2 by comet assay. However, a decrease in the nuclear index division in the 2.0 mg·mL-1 concentration and an increase of nucleoplasmic bridges in the 1.5 mg·mL-1 concentration were detected by CBMN-cyt assay indicating cytotoxic and mutagenic effects. In SRB assay, trimeroside showed weak antiproliferative activity against the cell lines.
Asunto(s)
Baccharis/química , Ciclohexenos/toxicidad , Glicósidos/toxicidad , Animales , Ensayo Cometa , Ciclohexenos/química , Ciclohexenos/aislamiento & purificación , Daño del ADN , Glicósidos/química , Glicósidos/aislamiento & purificación , Células HT29 , Células Hep G2 , Humanos , Células KB , Ratones , Pruebas de Micronúcleos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidad , Pruebas de ToxicidadRESUMEN
Perimenopause, a transition period that precedes menopause, is characterized by neuroendocrine, metabolic and behavioral changes, and is associated with increased vulnerability to affective disorders. The decrease in ovarian follicles during perimenopause contributes to a dynamic and complex hormonal milieu that is not yet well characterized. In rodents, 4-vinylcyclohexene diepoxide (VCD) induces a gradual depletion of ovarian follicles, modeling the transition to menopause in women. This study was aimed to investigate, in VCD-treated rats, the hormonal status and the behavior in the elevated plus-maze (EPM), a widely used test to assess anxiety-like behavior. From the postnatal day 28, rats were treated with VCD or vehicle for 15 days. At 80±5 days after the beginning of treatment the experiments were performed at proestrus and diestrus. In the first experiment rats were decapitated, ovary was collected and blood samples were taken for estradiol, progesterone, follicle stimulant hormone (FSH), testosterone, dihydrotestosterone (DHT) and corticosterone measurements. In the second experiment, rats were subjected to the EPM for 5 min, and behavioral categories recorded. Administration of VCD induced follicular depletion as well as an increase of the number of atretic follicles demonstrating the treatment efficacy. The transitional follicular depletion was accompanied by lower progesterone, testosterone and DHT with no changes in the FSH, estradiol and corticosterone plasma levels. On the EPM, rats showed decreased open arm exploration and increased risk assessment behavior, indicating increased anxiety. These findings show that administration of VCD to induce ovarian failure results in endocrine and anxiety-related changes that are similar to the symptoms exhibited by women during menopause transition. Thus, this model seems to be promising in the study of perimenopause-related changes.
Asunto(s)
Ansiedad/inducido químicamente , Ciclohexenos/toxicidad , Folículo Ovárico/efectos de los fármacos , Perimenopausia/efectos de los fármacos , Perimenopausia/psicología , Compuestos de Vinilo/toxicidad , Animales , Ansiedad/sangre , Corticosterona/sangre , Dihidrotestosterona/sangre , Modelos Animales de Enfermedad , Estradiol/sangre , Ciclo Estral/sangre , Femenino , Hormona Folículo Estimulante/sangre , Aprendizaje por Laberinto/efectos de los fármacos , Perimenopausia/sangre , Insuficiencia Ovárica Primaria/inducido químicamente , Progesterona/sangre , Ratas , Testosterona/sangreRESUMEN
In the search for larvicidal compounds against Aedes aegypti L. (Diptera: Culicidae), a collection of monoterpenes were selected and evaluated. R- and S-limonene exhibited the highest larvicidal potency (LC(50)=27 and 30 ppm, respectively), followed by γ-terpinene (LC(50)=56 ppm) and RS-carvone (LC(50)=118 ppm). Structural characteristics which may contribute to the understanding of the larvicidal activity of monoterpenes were empirically identified. The presence of heteroatoms in the basic hydrocarbon structure decreases larvicidal potency. Conjugated and exo double bonds appear to increase larvicidal potency. Replacement of double bonds by more reactive epoxides decreases the larvicidal potency. The presence of hydroxyls in the cyclic structure resulted in decreased potency, probably due to increased polarity indicanting that lipophilicity seems to play an important role in increasing the larvicidal potency in this set of compounds.
Asunto(s)
Aedes/efectos de los fármacos , Insecticidas/toxicidad , Monoterpenos/toxicidad , Animales , Ciclohexenos/toxicidad , Insecticidas/química , Larva/efectos de los fármacos , Limoneno , Monoterpenos/química , Relación Estructura-Actividad , Terpenos/toxicidadRESUMEN
A series of seven limonene β-amino alcohol derivatives has been regioselectively synthesised in moderate to good yields. Two of these compounds were found to be significantly effective against in vitro cultures of the Leishmania (Viannia) braziliensis promastigote form in the micromolar range. The activities found for 3b and 3f were about 100-fold more potent than the standard drug, Pentamidine, in the same test, while limonene did not display any activity. This is the first report of antileishmanial activity by limonene β-amino alcohol derivatives.
Asunto(s)
Animales , Ratones , Amino Alcoholes/síntesis química , Antiprotozoarios/síntesis química , Ciclohexenos/química , Leishmania braziliensis/efectos de los fármacos , Terpenos/química , Amino Alcoholes/farmacología , Amino Alcoholes/toxicidad , Antiprotozoarios/farmacología , Antiprotozoarios/toxicidad , Ciclohexenos/farmacología , Ciclohexenos/toxicidad , Estructura Molecular , Pruebas de Sensibilidad Parasitaria , Relación Estructura-Actividad , Terpenos/farmacología , Terpenos/toxicidadRESUMEN
Limonene, limonene oxide and eight beta-amino alcohol derivatives obtained by synthesis were investigated for the effect on egg hatchability and mortality rates of newly hatched larvae of the cattle tick Rhipicephalus (Boophilus) microplus. At the doses between 10 microg/ml and 2.5 microg/ml all the compounds were highly lethal to the larvae and some of them showed activity at lower concentrations. The effect on the eggs hatchability was observed in all the treatments.
Asunto(s)
Amino Alcoholes/toxicidad , Ciclohexenos/toxicidad , Insecticidas/toxicidad , Monoterpenos/toxicidad , Rhipicephalus/efectos de los fármacos , Terpenos/toxicidad , Amino Alcoholes/síntesis química , Animales , Monoterpenos Ciclohexánicos , Larva/efectos de los fármacos , Limoneno , Estructura Molecular , Óvulo/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
A series of seven limonene beta-amino alcohol derivatives has been regioselectively synthesised in moderate to good yields. Two of these compounds were found to be significantly effective against in vitro cultures of the Leishmania (Viannia) braziliensis promastigote form in the micromolar range. The activities found for 3b and 3f were about 100-fold more potent than the standard drug, Pentamidine, in the same test, while limonene did not display any activity. This is the first report of antileishmanial activity by limonene beta-amino alcohol derivatives.