RESUMEN
Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a phenol commonly found in grapes and wine, has been associated as protective in experimental models involving alterations in different neurotransmitter systems. However, studies are reporting that resveratrol could have adverse effects. This study evaluated if the association of a low dose of ketamine and resveratrol could induce behavioral manifestations associated with biochemical alterations. Moreover, the effects of treatment with resveratrol and/or ketamine on monoamine oxidase (MAO) activity, oxidative stress markers, and IL-6 levels in the brain were also investigated. Male Swiss mice received a low dose of ketamine (20 mg/kg) for 14 consecutive days, and resveratrol (10, 30, or 100 mg/kg) from day 8 up to day 14 of the experimental period, intraperitoneally. Locomotor, stereotyped behavior, Y-maze, novel recognition object test (NORT), and social interaction were quantified as well as ex vivo analysis of MAO activity, IL-6 levels, and oxidative stress markers (TBARS and total thiol levels) in brain tissues. Ketamine per se reduced the number of bouts of stereotyped behavior on day 8 of the experimental period. Resveratrol per se reduced the locomotor and exploratory activity in the open field, the time of exploration of new objects in the NORT, MAO-A activity in the striatum and increased the IL-6 levels in the cortex. These effects were attenuated when the mice were co-treated with ketamine and resveratrol. There was a decrease in MAO-A activity in the cortex of mice treated with ketamine + resveratrol 100 mg/kg. No significant alterations were found in oxidative stress markers. Resveratrol does not appear to cause summative effects with ketamine on behavioral alterations. However, the effect of resveratrol per se, mainly on locomotor and exploratory activity, should be better investigated.
Asunto(s)
Ketamina , Monoaminooxidasa , Estrés Oxidativo , Resveratrol , Animales , Resveratrol/farmacología , Resveratrol/administración & dosificación , Ketamina/farmacología , Masculino , Ratones , Estrés Oxidativo/efectos de los fármacos , Monoaminooxidasa/metabolismo , Monoaminooxidasa/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Conducta Exploratoria/efectos de los fármacos , Interleucina-6/metabolismo , Conducta Estereotipada/efectos de los fármacos , Antagonistas de Aminoácidos Excitadores/farmacología , Antagonistas de Aminoácidos Excitadores/administración & dosificación , Interacción Social/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/metabolismo , Reconocimiento en Psicología/efectos de los fármacos , Actividad Motora/efectos de los fármacosRESUMEN
The study investigated the protective effects of Hesperetin (HSP) and Hesperidin (HSD) on 1 methyl, 4 phenyl, 1,2,3,6 tetrahydropyridine hydrochloride (MPTP)-induced Parkinsonism in Drosophila melanogaster (D. melanogaster). After a lifespan study to select exposure time and concentrations, flies were co-exposed to MPTP (0.4â¯mg/g diet), Hesperetin (0.2 and 0.4â¯mg/g diet), and Hesperidin (0.1 and 0.4â¯mg/g) for 7 days. In addition to in vivo parameters, we assayed some markers of oxidative stress and antioxidant status (lipid peroxidation, protein carbonylation, thiol content, hydrogen peroxide, and nitrate/nitrite levels, mRNA expression of Keap-1 (Kelch-like ECH associated protein 1), /Nrf2 (Nuclear factor erythroid 2 related factor 2), catalase, and glutathione-S-transferase (GST) activities), and cholinergic (acetyl cholinesterase activity (AChE) and dopaminergic signaling content and the mRNA expression of tyrosine hydroxylase (TH), monoamine oxidase (MAO-like) activity). In addition to increasing the lifespan of flies, we found that both flavonoids counteracted the adverse effects of MPTP on survival, offspring emergence, and climbing ability of flies. Both flavonoids also reduced the oxidative damage on lipids and proteins and reestablished the basal levels of pro-oxidant species and activities of antioxidant enzymes in MPTP-exposed flies. These responses were accompanied by the normalization of the mRNA expression of Keap1/Nrf2 disrupted in flies exposed to MPTP. MPTP exposure also elicited changes in mRNA expression and content of TH as well as in MAO and AChE activity, which were reversed by HST and HSD. By efficiently hindering the oxidative stress in MPTP-exposed flies, our findings support the promising role of Hesperetin and Hesperidin as adjuvant therapy to manage Parkinsonism induced by chemicals such as MPTP.
Asunto(s)
Hesperidina , Enfermedad de Parkinson , Trastornos Parkinsonianos , Animales , Antioxidantes/farmacología , Antioxidantes/metabolismo , Drosophila melanogaster , Hesperidina/farmacología , Hesperidina/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/genética , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Flavonoides/farmacología , Trastornos Parkinsonianos/inducido químicamente , Trastornos Parkinsonianos/tratamiento farmacológico , Trastornos Parkinsonianos/prevención & control , Fenotipo , Monoaminooxidasa/metabolismo , ARN Mensajero/metabolismoRESUMEN
Schizophrenia is a chronic, debilitating mental illness that has not yet been completely understood. In this study, we aimed to investigate the effects of different doses of ketamine, a non-competitive NMDA receptor antagonist, on the positive- and negative-like symptoms of schizophrenia. We also explored whether these effects are related to changes in the immunoreactivity of GAD67, TH, and PPAR-γ in brain structures. To conduct the study, male mice received ketamine (20-40 mg/kg) or its vehicle (0.9 % NaCl) intraperitoneally for 14 consecutive days. We quantified stereotyped behavior, the time of immobility in the forced swimming test (FST), and locomotor activity after 7 or 14 days. In addition, we performed ex vivo analysis of the immunoreactivity of GAD, TH, and PPAR-γ, in brain tissues after 14 days. The results showed that ketamine administration for 14 days increased the grooming time in the nose region at all tested doses. It also increased immobility in the FST at 30 mg/kg doses and decreased the number of rearing cycles during stereotyped behavior at 40 mg/kg. These behavioral effects were not associated with changes in locomotor activity. We did not observe any significant alterations regarding the immunoreactivity of brain proteins. However, we found that GAD and TH were positively correlated with the number of rearing during the stereotyped behavior at doses of 20 and 30 mg/kg ketamine, respectively. GAD was positively correlated with the number of rearing in the open field test at a dose of 20 mg/kg. TH was inversely correlated with immobility time in the FST at a dose of 30 mg/kg. PPAR-γ was inversely correlated with the number of bouts of stereotyped behavior at a dose of 40 mg/kg of ketamine. In conclusion, the behavioral alterations induced by ketamine in positive-like symptoms were reproduced with all doses tested and appear to depend on the modulatory effects of TH, GAD, and PPAR-γ. Conversely, negative-like symptoms were associated with a specific dose of ketamine.
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Ketamina , Esquizofrenia , Ratones , Masculino , Animales , Ketamina/efectos adversos , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/inducido químicamente , PPAR gamma/metabolismo , Correlación de Datos , Natación , Conducta AnimalRESUMEN
Drosophila melanogaster is a model organism to study molecular mechanisms and the role of the genes and proteins involved in thermal nociception. Monoamines (i.e. dopamine) have been involved in temperature preference behavior in D. melanogaster. Therefore, we investigated whether the monoamines, particularly dopamine and serotonin, participate in the response to thermal nociceptive stimuli in D. melanogaster. Flies were treated with reserpine (an inhibitor of vesicular monoamines transporter, 3-300 µM), 3-Iodo-L-tyrosine (3-I-T, an inhibitor of tyrosine hydroxylase, 16.28-65.13 mM), and para-Chloro-DL-phenylalanine (PCPA, an inhibitor of tryptophan hydroxylase, 20-80 mM); then, the flies were subjected to tests of thermal tolerance and avoidance of noxious heat. Climbing behavior was used as a test to evaluate locomotor activity. Reserpine reduces the thermal tolerance profile of the D. melanogaster, as well as the avoidance of noxious heat and locomotor activity depending on the concentration. PCPA, but not 3-I-T, decreased heat tolerance and avoidance of noxious heat. These data suggest that monoamines, particularly serotonin, are associated with the impaired avoidance of noxious heat which could be related to the reduction of heat tolerance in D. melanogaster.
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Drosophila melanogaster , Termotolerancia , Animales , Drosophila melanogaster/metabolismo , Dopamina/metabolismo , Reserpina , Serotonina/metabolismoRESUMEN
Background and aim: This study investigated the effect of Kava extract (Piper methysticum), a medicinal plant that has been worldly used by its anxiolytic effects, on monoamine oxidase (MAO) activity of mice brain after 21 days of treatment as well as anxiolytic and locomotor behavior. Furthermore, the in vitro inhibitory profile of Kava extract on MAO-B activity of mouse brain was evaluated. Experimental procedure: Mice were treated with Kava extract (10, 40, 100 and 400 mg/kg) for 21 days by gavage. After behavioral analysis (plus maze test and open field), MAO activity in different mouse brain structures (cortex, hippocampus, region containing the substantia nigra and striatum) were performed. MAO-B inhibitory profile was characterized in vitro. Results: The treatment with Kava extract (40 mg/kg) increased the percentage of entries of mice into the open arms. Ex vivo analysis showed an inhibition on MAO-B activity caused by Kava extract in cortex (10 mg/kg) and in the region containing the substantia nigra (10 and 100 mg/kg). In vitro, Kava extract also reversibly inhibited MAO-B activity with IC50 = 14.62 µg/mL and, increased Km values at the concentrations of 10 and 30 µg/mL and decreased Vmax value at 100 µg/mL. Conclusion: Kava extract showed different effects on MAO-B isoform depending on the brain structure evaluated. Therefore, the use of Kava extract could be promissory in pathologies where MAO-B is the pharmacological target.
RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Kava extract (Piper methysticum) is a phytotherapic mainly used for the treatment of anxiety. Although the reported effects of Kava drinking improving psychotic symptoms of patients when it was introduced to relieve anxiety in aboriginal communities, its effects on models of psychosis-like symptoms are not investigated. AIM OF THE STUDY: To investigate the effects of Kava extract on behavioral changes induced by amphetamine (AMPH) and its possible relation with alterations in monoamine oxidase (MAO) activity. MATERIALS AND METHODS: Mice received vehicle or Kava extract by gavage and, 2 h after vehicle or AMPH intraperitoneally. Twenty-five minutes after AMPH administration, behavioral (elevated plus maze, open field, stereotyped behavior, social interaction and Y maze) and biochemical tests (MAO-A and MAO-B activity in cortex, hippocampus and striatum) were sequentially evaluated. RESULTS: Kava extract exhibited anxiolytic effects in plus maze test, increased the locomotor activity of mice in open field test and decreased MAO-A (in cortex) and MAO-B (in hippocampus) activity of mice. Kava extract prevented the effects of AMPH on stereotyped behavior and, the association between Kava/AMPH increased the number of entries into arms in Y maze test as well as MAO-B activity in striatum. However, Kava extract did not prevent hyperlocomotion induced by AMPH in open field test. The social interaction was not modified by Kava extract and/or AMPH. CONCLUSION: The results showed that Kava extract decreased the stereotyped behavior induced by AMPH at the same dose that promotes anxiolytic effects, which could be useful to minimize the psychotic symptoms in patients.
Asunto(s)
Anfetamina/farmacología , Kava/química , Extractos Vegetales/farmacología , Conducta Estereotipada/efectos de los fármacos , Animales , Ansiolíticos/farmacología , Ansiedad/tratamiento farmacológico , Conducta Animal/efectos de los fármacos , Locomoción/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , RatonesRESUMEN
Haloperidol is a typical antipsychotic drug commonly used to treat a broad range of psychiatric disorders related to dysregulations in the neurotransmitter dopamine (DA). DA modulates important physiologic functions and perturbations in Caenorhabditis elegans (C. elegans) and, its signaling have been associated with alterations in behavioral, molecular, and morphologic properties in C. elegans. Here, we evaluated the possible involvement of dopaminergic receptors in the onset of these alterations followed by haloperidol exposure. Haloperidol increased lifespan and decreased locomotor behavior (basal slowing response, BSR, and locomotion speed via forward speed) of the worms. Moreover, locomotion speed recovered to basal conditions upon haloperidol withdrawal. Haloperidol also decreased DA levels, but it did not alter neither dop-1, dop-2, and dop-3 gene expression, nor CEP dopaminergic neurons' morphology. These effects are likely due to haloperidol's antagonism of the D2-type DA receptor, dop-3. Furthermore, this antagonism appears to affect mechanistic pathways involved in the modulation and signaling of neurotransmitters such as octopamine, acetylcholine, and GABA, which may underlie at least in part haloperidol's effects. These pathways are conserved in vertebrates and have been implicated in a range of disorders. Our novel findings demonstrate that the dop-3 receptor plays an important role in the effects of haloperidol.
Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Haloperidol/metabolismo , Receptores de Dopamina D2/metabolismo , Animales , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/genética , Dopamina/metabolismo , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Haloperidol/farmacología , Locomoción/efectos de los fármacos , Longevidad/efectos de los fármacos , Modelos Biológicos , Mutación/genética , Degeneración Nerviosa/patología , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
This study evaluated the effect of (+)-catechin, a polyphenolic compound, on orofacial dyskinesia (OD) induced by reserpine in mice. The potential modulation of monoaminoxidase (MAO) activity, tyrosine hydroxylase (TH) and glutamic acid decarboxylase (GAD67) immunoreactivity by catechin were used as biochemical endpoints. The interaction of catechin with MAO-A and MAO-B was determined in vitro and in silico. The effects of catechin on OD induced by reserpine (1 mg/kg for 4 days, subcutaneously) in male Swiss mice were examined. After, catechin (10, 50 or 100 mg/kg, intraperitoneally) or its vehicle were given for another 20 days. On the 6th, 8th, 15th and 26th day, vacuous chewing movements (VCMs) and locomotor activity were quantified. Biochemical markers (MAO activity, TH and GAD67 immunoreactivity) were evaluated in brain structures. In vitro, catechin inhibited both MAO isoforms at concentrations of 0.34 and 1.03 mM being completely reversible for MAO-A and partially reversible for MAO-B. Molecular docking indicated that the catechin bound in the active site of MAO-A, while in the MAO-B it interacted with the surface of the enzyme in an allosteric site. In vivo, reserpine increased the VCMs and decreased the locomotor activity. Catechin (10 mg/kg), decreased the number of VCMs in the 8th day in mice pre-treated with reserpine without altering other behavioral response. Ex vivo, the MAO activity and TH and GAD67 immunoreactivity were not altered by the treatments. Catechin demonstrated a modest and transitory protective effect in a model of OD in mice.
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Catequina/uso terapéutico , Discinesias/tratamiento farmacológico , Discinesias/metabolismo , Masticación/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Reserpina/toxicidad , Animales , Antipsicóticos/toxicidad , Catequina/farmacología , Relación Dosis-Respuesta a Droga , Masculino , Masticación/fisiología , Ratones , Simulación del Acoplamiento Molecular/métodos , Inhibidores de la Monoaminooxidasa/farmacología , Inhibidores de la Monoaminooxidasa/uso terapéutico , Actividad Motora/fisiología , Estructura Secundaria de Proteína , Resultado del TratamientoRESUMEN
The production of reactive species over physiological levels associated to pathogenic bacteria could represent a high risk for many diseases. The Rosmarinus officinalis L. is used around the world due its pharmacological proprieties. So, in this study our aim is to test for the first time if R. officinalis L. extract (eeRo) and its fractions (DCM, EA, ButOH) could have better or similar antioxidant action to standars and among themselves in vitro or ex vivo, in brain, stomach and liver of rats. Moreover, we intend to clarify their possible effects on pathogenic bacteria. The eeRo was obtained from the dried leaves subjected to an alcoholic extraction and fractioned. The quantification of the constituents of eeRo and fractions were done by HPLC. The antioxidant proprieties of R. officinalis was analyzed by DPPHâ¢- radical scavenging, total antioxidant, dichlorofluorescein, lipid peroxidation and sodium nitroprusside -induced lipid peroxidation assays. The Minimum inhibitory concentrations of R. officinalis L. were tested with standard strains of danger bacteria. The eeRo, DCM, EA had significant total antioxidant and DPPHâ¢- radical scavenging activities. The DCM and eeRo got significant effects against basal levels of reactive species in liver, stomach and brain. The eeRo and DCM protected the liver and brain against lipid peroxidation. The eeRo, DCM, EA and ButOH had inhibitory effect in the Gram-positive and Gram-negative bacteria. In general way, the DCM and eeRo had the best antioxidant and antibacterial effects among all tested fractions.
RESUMEN
Oxidative stress occurs due to an imbalance between antioxidant defenses and pro-oxidant agents in brain. This condition has been associated to the pathogenesis of several brain diseases; therefore, increasing the use of compounds that exert antioxidant activity. Thus, the objective of this study was to evaluate, in vitro, the effect of isoflavones in: (1) lipid peroxidation, catalase activity and thiol groups in the presence of pro-oxidants: sodium nitroprusside or Fe2+/EDTA complex in rat brain homogenates; (2) the activity of the enzyme monoamine oxidase (MAO). As a result, the isoflavones reduced lipid peroxidation in a manner dependent on the concentration and protected against the reduction of catalase activity as well as the induced thiol oxidation in brain tissue. In addition, isoflavones inhibited MAO activity (MAO-A and MAO-B). Taken together, our results showed that isoflavones avoided oxidative stress and decreased the MAO activity, suggesting a promissory use in the treatment of neurodegenerative diseases.
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Isoflavonas/metabolismo , Isoflavonas/uso terapéutico , Inhibidores de la Monoaminooxidasa/metabolismo , Animales , Encéfalo/metabolismo , Catalasa/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Monoaminooxidasa/metabolismo , Inhibidores de la Monoaminooxidasa/farmacología , Nitroprusiato/farmacología , Oxidación-Reducción , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/farmacologíaRESUMEN
Thimerosal (THIM) is a well-established antifungal and antiseptic agent widely used as a preservative in vaccines. Recent studies identified the neurotoxic effects of THIM, including malfunction of the monoaminergic system. However, the underlying cytotoxic mechanisms are not well understood. Here we used the fruit fly Drosophila melanogaster to investigate the mechanisms of THIM-induced neurotoxicity. We focused on the dopaminergic system, and the rate-limiting enzyme tyrosine hydroxylase (DmTyrH), to test the hypothesis that THIM can impair dopamine (DA) homeostasis and subsequently cause dysfunction. We studied the effect of THIM by feeding 1-2 day old flies (both sexes) food supplemented with 25 µM THIM for 4 days and determined THIM-induced effects on survival, oxidative stress, and metabolic activity based on MTT assay and acetylcholinesterase (AChE) activity. Our results demonstrate that D. melanogaster exposed to THIM present changes in DmTyrH expression and activity, together with altered DA levels that led to impaired motor behavior. These phenotypes were accompanied by an increase in oxidative stress, with a decrease in MTT reduction, in AChE activity, and also in survival rate. These findings suggest an initiating and primary role for THIM-mediated DmTyrH dysfunction that leads to impaired DA function and behavioral abnormalities, ultimately causing oxidative stress-related neurotoxicity.
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Dopamina/metabolismo , Timerosal/farmacología , Tirosina 3-Monooxigenasa/metabolismo , Animales , Drosophila melanogaster , Femenino , Glutatión Transferasa/metabolismo , Masculino , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Reductasa de Tiorredoxina-Disulfuro/metabolismoRESUMEN
Curcumin, the main bioactive polyphenolic compound in Curcuma longa L. rhizomes has a wide range of bioactive properties. Curcumin presents low solubility in water and thus limited bioavailability, which decreases its applicability. In this study, cytotoxic effects of curcumin solid dispersions (CurSD) were evaluated against tumor (breast adenocarcinoma and lung, cervical and hepatocellular carcinoma) and non-tumor (PLP2) cells, while cytotoxic and genotoxic effects were evaluated in Allium cepa. The effect of the CurSD on the acetylcholinesterase (AChE), butyrylcholinesterase (BChE), glutathione S-transferase (GST), and monoamine oxidase (MAO A-B) enzymes was determined, as well as its capacity to inhibit the oxidative hemolysis (OxHLIA) and the formation of thiobarbituric acid reactive substances (TBARS). CurSD are constituted by nanoparticles that are readily dispersible in water, and inhibited 24% and 64% of the AChE and BChE activity at 100⯵M, respectively. GST activity was inhibited at 30⯵M while MAO-A and B activity were inhibited at 100⯵M. CurSD showed cytotoxicity against all the tested tumor cell lines without toxic effects for non-tumor cells. No cytotoxic and genotoxic potential was detected with the Allium cepa test. CurSD maintained the characteristics of free curcumin on the in vitro modulation of important enzymes without appreciable toxicity.
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Antioxidantes/farmacología , Carcinógenos/farmacología , Curcumina/farmacología , Mutágenos/farmacología , Animales , Línea Celular Tumoral , Formas de Dosificación , Inhibidores Enzimáticos/farmacología , Hemólisis/efectos de los fármacos , Humanos , Ratones , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Cebollas/efectos de los fármacos , Oxidación-Reducción , Células RAW 264.7 , Ratas , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
Methylglyoxal (MG) is a α-dycarbonyl compound derived mainly from glycolysis, whose accumulation is harmful for cells and tissues. Here, we evaluated the cytotoxic effects induced by MG in leukocytes after an acute exposure, measuring as endpoints of toxicity some markers of oxidative stress and programmed cell death. Human leukocytes were isolated and incubated with MG at concentrations ranging from 0.1 to 10â¯mM for 2.5â¯h, and subsequently prepared for assays based in flow cytometry, gene expression and immunoreactivity profile. The cells exposed to higher concentrations of MG had significant loss of viability, increased reactive species (RS) production and apoptosis/necrosis rate. These phenomena were accompanied by morphological changes (increased size and granularity) and disruption in mRNA expression of antioxidant, apoptotic and glycation-responsive genes, particularly: Nrf2 (Nuclear factor (erythroid-derived 2)-like 2), SOD1 (CuZn-superoxide dismutase), SOD2 (Mn-superoxide dismutase), GSR (glutathione-S-reductase), BAX (BAX-associated X protein), BCL-2 (BCL-2-associated X protein), AIF (apoptosis inducing factor), GLO-1 (glyoxalase-1) and RAGE (receptor for advanced glycation end products). The mRNA expression of CASP 9 and CASP 3 (caspase-9 and 3) as well as the immunoreactivity of proteins were not changed by MG. Collectively, our data provide evidence that MG activates programmed cell death pathways in leukocytes and that this effect seems to be associated with disturbances in cell redox signaling.
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Leucocitos/efectos de los fármacos , Piruvaldehído/toxicidad , Adulto , Apoptosis/fisiología , Muerte Celular/efectos de los fármacos , Muerte Celular/fisiología , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Leucocitos/metabolismo , Masculino , Adulto JovenRESUMEN
Ultraviolet B radiation represents 10% of the total UV radiation that reaches the Earth's surface, being the primary responsible for the biological effects related to skin cancer and photoaging. Ilex Paraguariensis A. St. Hil., known as Yerba mate (YM), is a native tree of South America whose polyphenols in its leaves are described to exhibit photochemoprotective effect and are employed in the treatment of cancer. Additionally, the polyphenols are used to prevent lipid peroxidation and reduce the UV-induced damage, which ultimately decreases the oxidative stress. Thus, the present study aimed to characterize a new YM extract, evaluate the extract cytotoxicity and develop a formulation containing YM extract to prevent UVB-induced damage in mice skin. The YM extract showed high levels of polyphenols, flavonoids, and tannins and exhibited excellent antioxidant activity. Its main components were suggested as chlorogenic acid (1.92%) and caffeic acid (0.41%). Besides, YM extract did not exhibit cytotoxicity in fibroblasts and decreased the activity of myeloperoxidase and metalloproteinase-2 after acute UVB exposure. As a result, the formulation containing the YM extract showed a potential photochemoprotective.
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Ilex paraguariensis/química , Metaloendopeptidasas/efectos de los fármacos , Peroxidasa/efectos de los fármacos , Extractos Vegetales/farmacología , Rayos Ultravioleta , Administración Tópica , Animales , Ácidos Cafeicos , Ácido Clorogénico , Metaloendopeptidasas/metabolismo , Ratones , Peroxidasa/metabolismo , Polifenoles , Sustancias ProtectorasAsunto(s)
Actividad Motora/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Oxidopamina/toxicidad , Trastornos Parkinsonianos/tratamiento farmacológico , Silimarina/farmacología , Animales , Conducta Animal/efectos de los fármacos , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/inmunología , Masculino , Ratones , Estrés Oxidativo/efectos de los fármacos , Trastornos Parkinsonianos/inducido químicamente , Distribución AleatoriaRESUMEN
Excessive production of reactive species in living cells usually has pathological effects. Consequently, the synthesis of compounds which can mimic the activity of antioxidant enzymes has inspired great interest. In this study, a variety of diselenoamino acid derivatives from phenylalanine and valine were tested to determine whether they could be functional mimics of glutathione peroxidase (GPx) and substrates for liver thioredoxin reductase (TrxR). Diselenides C and D showed the best GPx mimicking properties when compared with A and B. We suppose that the catalytic activity of diselenide GPx mimics depends on the steric effects, which can be influenced by the number of carbon atoms between the selenium atom and the amino acid residue and/or by the amino acid lateral residue. Compounds C and D stimulated NADPH oxidation in the presence of partially purified hepatic mammalian TrxR, indicating that they are substrates for TrxR. Our study indicates a possible dissociation between the two pathways for peroxide degradation (i.e., via a substrate for TrxR or via mimicry of GPx) for compounds tested in this study, except for PhSeSePh, and the antioxidant activity of diselenoamino acids can also be attributed to their capacity to mimic GPx and to be a substrate for mammalian TrxR.
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Materiales Biomiméticos/química , Materiales Biomiméticos/metabolismo , Simulación por Computador , Glutatión Peroxidasa/metabolismo , Compuestos de Organoselenio/química , Compuestos de Organoselenio/metabolismo , Reductasa de Tiorredoxina-Disulfuro/metabolismo , Animales , Dominio Catalítico , Masculino , Modelos Moleculares , Simulación del Acoplamiento Molecular , Oxidación-Reducción , Ratas , Reductasa de Tiorredoxina-Disulfuro/químicaRESUMEN
Tardive dyskinesia (TD) is a common adverse effect observed in patients with long-term use of typical antipsychotic medications. A vacuous chewing movement (VCM) model induced by haloperidol has been used to study these abnormalities in experimental animals. The cause of TD and its treatment remain unknown, but several lines of evidence suggest that dopamine receptor supersensitivity and gamma-aminobutyric acid (GABA) insufficiency play important roles in the development of TD. This study investigated the effects of treatment with the GABA-mimetic drug gabapentin on the development of haloperidol-induced VCMs. Male mice received vehicle, haloperidol (1.5â¯mg/kg), or gabapentin (GBP, 100â¯mg/kg) intraperitoneally during 28 consecutive days. Quantification of VCMs was performed before treatment (baseline) and on day 28, and an open-field test was also conducted on the 28th day of treatment. The administration of gabapentin prevented the manifestation of haloperidol-induced VCMs. Treatment with haloperidol alone reduced the locomotor activity in the open-field test that was prevented by co-treatment with gabapentin. We did not find any differences among the groups nor in the tyrosine hydroxylase (TH) or glutamic acid decarboxylase (GAD) immunoreactivity or monoamine levels in the striatum of mice. These results suggest that treatment with gabapentin, an analog of GABA, can attenuate the VCMs induced by acute haloperidol treatment in mice without alterations in monoamine levels, TH, or GAD67 immunoreactivity in the striatum.
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Antagonistas de Dopamina/toxicidad , Moduladores del GABA/farmacología , Gabapentina/farmacología , Haloperidol/toxicidad , Masticación/efectos de los fármacos , Animales , Ansiolíticos/farmacología , Antidiscinéticos/toxicidad , Masculino , Masticación/fisiología , RatonesRESUMEN
(-)-α-Bisabolol (BISA) is a sesquiterpene alcohol, which has several recognized biological activities, including anti-inflammatory, anti-irritant, and antibacterial properties. In the present study, we investigated the influence of BISA (5, 25, and 250 µmol/L) on rotenone (500 µmol/L)-induced toxicity in Drosophila melanogaster for 7 days. BISA supplementation significantly decreased rotenone-induced mortality and locomotor deficits. The loss of motor function induced by rotenone correlated with a significant change in stress response factors; it decreased thiol levels, inhibited mitochondria complex I, and increased the mRNA expression of antioxidant marker proteins such as superoxide dismutase (SOD), catalase (CAT), and the keap1 gene product. Taken together, our findings indicate that the toxicity of rotenone is likely due to the direct inhibition of complex I activity, resulting in a high level of oxidative stress. Dietary supplementation with BISA affected the expression of SOD mRNA only at a concentration of 250 µmol/L, and did not affect any other parameter measured. Our results showed a protective effect of BISA on rotenone-induced mortality and locomotor deficits in Drosophila; this effect did not correlate with mitochondrial complex I activity, but may be related to the antioxidant protection afforded by eliminating superoxide generated as a result of rotenone-induced mitochondrial dysfunction.
Asunto(s)
Drosophila melanogaster/efectos de los fármacos , Sustancias Protectoras/farmacología , Rotenona/toxicidad , Sesquiterpenos/farmacología , Animales , Catalasa/genética , Catalasa/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/enzimología , Drosophila melanogaster/genética , Complejo I de Transporte de Electrón/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Proteína 1 Asociada A ECH Tipo Kelch/genética , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Sesquiterpenos Monocíclicos , Actividad Motora/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transducción de Señal/efectos de los fármacos , Compuestos de Sulfhidrilo/metabolismo , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Análisis de SupervivenciaRESUMEN
Considering the antioxidant properties of sodium selenite (Na2SeO3) and the involvement of oxidative stress events in paraquat-induced neurotoxicity, this study investigated the protective effect of dietary Na2SeO3 on biochemical and behavioral parameters of zebrafish exposed to paraquat (PQ). Fish were pretreated with a Na2SeO3 diet for 21 days and then PQ (20 mg/kg) was administered intraperitoneally with six injections for 16 days. In the novel tank test, the Na2SeO3 diet prevented the locomotor impairments, as well as the increase in the time spent in the top area of the tank, and the exacerbation of freezing episodes. In the preference for conspecifics and in the mirror-induced aggression (MIA) tasks, Na2SeO3 prevented the increase in the latency to enter the area closer to conspecifics and the agonistic behavior of PQ-treated animals, respectively. Na2SeO3 prevented the increase of carbonylated protein (CP), reactive oxygen species (ROS), and nitrite/nitrate (NOx) levels, as well as the decrease in non-protein thiols (NPSH) levels. Regarding the antioxidant enzymatic defenses, Na2SeO3 prevented the increase in catalase (CAT) and glutathione peroxidase (GPx) activities caused by PQ. Altogether, dietary Na2SeO3 improves behavioral and biochemical function impaired by PQ treatment in zebrafish, by modulating not only redox parameters, but also anxiety- and aggressive-like phenotypes in zebrafish.
Asunto(s)
Herbicidas/toxicidad , Fármacos Neuroprotectores/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Paraquat/toxicidad , Selenito de Sodio/administración & dosificación , Animales , Locomoción/efectos de los fármacos , Locomoción/fisiología , Estrés Oxidativo/fisiología , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Pez CebraRESUMEN
The high levels of oxidative stress and inflammation can be present in the etiology of degenerative intestinal pathologies associated with ethanol ingestion. The Rosmarinus officinalis L. has exhibited several physiological and medicinal activities. In this investigation, we intended to clarify, for the first time, the antioxidant and anti-inflammatory effects of ethanolic extract of Rosmarinus officinalis L. (eeRo) against an acute damage induced by ethanol, specifically in the small intestine of rats. The rats were treated three times, at every 24â¯h, with eeRo at 500-1000â¯mg/kg or vehicle, oral gavage. All groups got a single dose of ethanol (2â¯ml/kg), oral gavage, after 36â¯h of fasting and 1â¯h after the last dose of eeRo or vehicle administration. We performed the mensuration of oxidative stress profile in lipid peroxidation in serum and intestine; Na+/K+ ATPase, catalase, and superoxide dismutase activities assays only in intestine; and anti-inflammatory evidences of eeRo in myeloperoxidase activity assay only in the intestine. The eeRo was able to protect the animals against the lipid peroxidation in serum and intestine. It prevented the reduction in Na+/K+ ATPase and catalase levels induced by ethanol in the intestine. In addition, eeRo increased the superoxide dismutase activity when compared to control and protected the intestine against elevations in myeloperoxidase activity caused by ethanol. Our results suggested that eeRo exerted a significant intestinal protective effect by antioxidant and anti-inflammatory mechanisms. Thus, the eeRo represented a promising agent against intestinal lesions induced by ethanol.