RESUMEN
Hydrogen sulfide plays an important role in the regulation of the cardiovascular system, insulin secretion, and glucose homeostasis. The aim of the present study was to examine the effects of chronic treatment with sodium hydrosulfide (NaHS), L-Cysteine (L-Cys) and DL-Propargylglycine (DL-PAG) on the changes induced by a high-fat diet (HFD) in zoometric and metabolic variables as well as cardiovascular changes such as hypertension and sympathetic hyperactivity. For this purpose, male Wistar rats were fed a normal fat diet (NFD) or HFD for 12 weeks. Next, the HFD rats were divided into 5 subgroups which received daily i.p. injections during 4 weeks of: (1) nothing (no injection, Control); (2) vehicle (PBS; 1ml/kg); (3) NaHS (5.6â¯mg/kg); (4) L-Cys (300mg/kg); or (5) DL-PAG (1mg/kg). Then, an oral glucose tolerance test, hormone serum levels and blood pressure were determined. The cardiovascular responses to stimulation of the vasopressor sympathetic tone or intravenous administration of the agonists noradrenaline (α1/2-adrenoceptors), methoxamine (α1-adrenoceptors) and UK 14,304 (α2-adrenoceptors) were determined in pithed rats. Lastly, the heart, liver and adipose tissue were weighted. HFD significantly increased: (1) zoometric variables, which were decreased by NaHS and L-Cys; (2) metabolic variables, ameliorated by DL-PAG; (3) haemodynamic variables, which were reversed by NaHS and L-Cys; and (4) the vasopressor responses induced by sympathetic stimulation, which were diminished by NaHS and L-Cys. In conclusion, chronic treatment with NaHS and L-Cys are effective in reducing adipose tissue and ameliorating the cardiovascular changes induced by obesity; meanwhile, DL-PAG ameliorates metabolic variables.
Asunto(s)
Sistema Cardiovascular/efectos de los fármacos , Cisteína/administración & dosificación , Cisteína/farmacología , Dieta Alta en Grasa/efectos adversos , Recuperación de la Función/efectos de los fármacos , Sulfuros/administración & dosificación , Sulfuros/farmacología , Agonistas de Receptores Adrenérgicos alfa 1/farmacología , Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Animales , Sistema Cardiovascular/fisiopatología , Hemodinámica/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
Fresh aqueous extracts (AGEs) and several thioallyl compounds (TACs) from garlic have an important antimicrobial activity that likely involves their interaction with exposed thiol groups at single aminoacids or target proteins. Since these groups are present in Giardia duodenalis trophozoites, in this work we evaluated the anti-giardial activity of AGE and several garlic's TACs. In vitro susceptibility assays showed that AGE affected trophozoite viability initially by a mechanism impairing cell integrity and oxidoreductase activities while diesterase activities were abrogated at higher AGE concentrations. The giardicidal activities of seven TACs were related to the molecular descriptor HOMO (Highest Occupied Molecular Orbital) energy and with their capacity to modify the -SH groups exposed in giardial proteins. Interestingly, the activity of several cysteine proteases in trophozoite lysates was inhibited by representative TACs as well as the cytopathic effect of the virulence factor giardipain-1. Of these, allicin showed the highest anti-giardial activity, the lower HOMO value, the highest thiol-modifying activity and the greatest inhibition of cysteine proteases. Allicin had a cytolytic mechanism in trophozoites with subsequent impairment of diesterase and oxidoreductase activities in a similar way to AGE. In addition, by electron microscopy a marked destruction of plasma membrane and endomembranes was observed in allicin-treated trophozoites while cytoskeletal elements were not affected. In further flow cytometry analyses pro-apoptotic effects of allicin concomitant to partial cell cycle arrest at G2 phase with the absence of oxidative stress were observed. In experimental infections of gerbils, the intragastric administration of AGE or allicin decreased parasite numbers and eliminated trophozoites in experimentally infected animals, respectively. These data suggest a potential use of TACs from garlic against G. duodenalis and in the treatment of giardiasis along with their additional benefits in the host's health.
Asunto(s)
Compuestos Alílicos/farmacología , Antiprotozoarios/farmacología , Ajo/química , Giardia lamblia/efectos de los fármacos , Giardiasis/tratamiento farmacológico , Extractos Vegetales/farmacología , Sulfuros/farmacología , Trofozoítos/efectos de los fármacos , Compuestos Alílicos/administración & dosificación , Compuestos Alílicos/aislamiento & purificación , Animales , Antiprotozoarios/administración & dosificación , Antiprotozoarios/aislamiento & purificación , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/farmacología , Gerbillinae , Carga de Parásitos , Pruebas de Sensibilidad Parasitaria , Extractos Vegetales/administración & dosificación , Extractos Vegetales/aislamiento & purificación , Sulfuros/administración & dosificación , Sulfuros/aislamiento & purificación , Resultado del TratamientoRESUMEN
We aimed to evaluate the effects of detorsion and Allium sativum (garlic oil) treatment on the ovarian reserve in an ovarian torsion model. Ovarian torsion may lead to loss of ovarian tissue and infertility. It is an experimental rat study that was carried out on 16 sets of ovaries each, one for treatment group and a control group. In the control group, the procedure involved only the surgically opening and closing the abdomen. Bilateral adnexal torsion/detorsion was performed after a 3-hour ischemia period for the detorsion-only group. The detorsion + Allium sativum group received a 5 ml/kg dose of Allium sativum intraperitoneally, 2 hours before surgery. After the second surgery, removed ovarian samples were evaluated for follicle counts, damage scores and other parameters. Primordial, preantral, small antral and large antral follicle counts were significantly higher in the detorsion + Allium sativum group. Degeneration, congestion, hemorrhage ,inflammation and total damage scores were significantly elevated in the detorsion only group compared to those for the detorsion + Allium sativum group. Finally, there was a significant correlation between AMH alterations and postoperative, preantral follicle count (p<0.05). As a conclusion detorsion + Allium sativum treatment may be effective in protecting the ovarian reserve after torsion.
Intentamos evaluar los efectos de la detorsión y el tratamiento con Allium sativum (aceite de ajo) en la reserva ovárica en un modelo de torsión ovárica. La torsión ovárica puede ocasionar pérdida de tejido ovárico e infertilidad. Este es un estudio experimental en ratas que se llevó a cabo en 16 sets de ovarios para cada grupo: tratamiento y control. En el grupo control, el procedimiento involucró solamente la apertura y el cierre quirúrgicos del abdomen. La torsión / detorsión anexial bilateral se realizó después de un período de isquemia de 3 horas para el grupo de solo detorsión. El grupo de detorsión + Allium sativum recibió una dosis de 5 ml / kg de Allium sativum por vía intraperitoneal, 2 horas antes de la cirugía. Después de la segunda cirugía, las muestras ováricas eliminadas se evaluaron para recuentos de folículos, puntajes de daño y otros parámetros. Los recuentos de folículos antrales primordiales, preantrales, antrales pequeños y grandes fueron significativamente mayores en el grupo con detorsión + Allium sativum. Los puntajes de degeneración, congestión, hemorragia, inflamación y daño total fueron significativamente elevados en el grupo de solo detorsión, en comparación con los del grupo de detorsión + Allium sativum. Finalmente, hubo una correlación significativa entre las alteraciones de AMH y el recuento de folículos preantrales postoperatorios (p <0,05). Como conclusión, el tratamiento con detorsión + Allium sativum puede ser eficaz para proteger la reserva ovárica después de la torsión.
Asunto(s)
Animales , Femenino , Ratas , Enfermedades del Ovario/tratamiento farmacológico , Ovario/efectos de los fármacos , Sulfuros/administración & dosificación , Compuestos Alílicos/administración & dosificación , Ajo/química , Anomalía Torsional , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras , Modelos Animales de Enfermedad , Reserva Ovárica/efectos de los fármacosRESUMEN
BACKGROUND: Hydrogen sulfide (H2 S) is a potentially deadly gas that naturally occurs in petroleum and natural gas. The Occupational Health and Safety Administration cites H2 S as a leading cause of workplace gas inhalation deaths. Mass casualties of H2 S toxicity may be caused by exposure from industrial accidents or release from oil field sites. H2 S is also an attractive terrorism tool because of its high toxicity and ease with which it can be produced. Several potential antidotes have been proposed for hydrogen sulfide poisoning but none have been completely successful. OBJECTIVE: The objective was to compare treatment response assessed by the time to spontaneous ventilation among groups of swine with acute H2 S-induced apnea treated with intravenous (IV) cobinamide (4 mg/kg in 0.8 mL of 225 mmol/L solution), IV hydroxocobalamin (4 mg/kg in 5 mL of saline), or saline alone. METHODS: Twenty-four swine (45-55 kg) were anesthetized, intubated, and instrumented with continuous femoral and pulmonary artery pressure monitoring. After stabilization, anesthesia was adjusted such that animals would spontaneously ventilate with an FiO2 of 0.21. Sodium hydrosulfide (NaHS; concentration of 8 mg/mL) was begun at 1 mg/kg/min until apnea was confirmed for 20 seconds by capnography. This infusion rate was sustained for 1.5 minutes postapnea and then decreased to a maintenance rate for the remainder of the study to replicate sustained clinical exposure. Animals were randomly assigned to receive cobinamide (4 mg/kg), hydroxocobalamin (4 mg/kg), or saline and monitored for 60 minutes beginning 1 minute postapnea. G* power analysis using the Z-test determined that equal group sizes of eight animals were needed to achieve a power of 80% in detecting a 50% difference in return to spontaneous ventilations at α = 0.05. RESULTS: There were no significant differences in baseline variables. Moreover, there were no significant differences in the mg/kg dose of NaHS (5.6 mg/kg; p = 0.45) required to produce apnea. Whereas all of the cobinamide-treated animals survived (8/8), none of the control (0/8) or hydroxocobalamin (0/8)-treated animals survived. Mean (±SD) time to spontaneous ventilation in the cobinamide-treated animals was 3.2 (±1.1) minutes. CONCLUSIONS: Cobinamide successfully rescued the severely NaHS-poisoned swine from apnea in the absence of assisted ventilation.
Asunto(s)
Antídotos/uso terapéutico , Apnea/tratamiento farmacológico , Cobamidas/uso terapéutico , Sulfuro de Hidrógeno/envenenamiento , Hidroxocobalamina/uso terapéutico , Administración Intravenosa , Animales , Apnea/inducido químicamente , Cobamidas/administración & dosificación , Cobamidas/farmacología , Modelos Animales de Enfermedad , Femenino , Hidroxocobalamina/farmacología , Cloruro de Sodio/administración & dosificación , Sulfuros/administración & dosificación , Sus scrofa , PorcinosRESUMEN
Spontaneously hypertensive rats (SHR) display autonomic imbalance and abnormal body temperature (Tb) adjustments. Hydrogen sulfide (H2S) modulates hypoxia-induced hypothermia, but its role in SHR thermoregulation is unknown. We tested the hypothesis that SHR display peculiar thermoregulatory response to hypoxia and that endogenous H2S overproduced in the caudal nucleus of the solitary tract (NTS) of SHR modulates this response. SHR and Wistar rats were microinjected into the fourth ventricle with aminooxyacetate (AOA, H2S-synthezing enzyme inhibitor) or sodium sulfide (Na2S, H2S donor) and exposed to normoxia (21% inspired O2) or hypoxia (10% inspired O2, 30 min). Tb was continuously measured, and H2S production rate was assessed in caudal NTS homogenates. In both groups, AOA, Na2S, or saline (i.e., control; 1 µL) did not affect euthermia. Hypoxia caused similar decreases in Tb in both groups. AOA presented a longer latency to potentiate hypoxic hypothermia in SHR. Caudal NTS H2S production rate was higher in SHR. We suggest that increased bioavailability of H2S in the caudal NTS of SHR enables the adequate modulation of excitability of peripheral chemoreceptor-activated NTS neurons that ultimately induce suppression of brown adipose tissue thermogenesis, thus accounting for the normal hypoxic hypothermia.
Asunto(s)
Regulación de la Temperatura Corporal , Sulfuro de Hidrógeno/metabolismo , Hipotermia Inducida , Hipoxia/fisiopatología , Ácido Aminooxiacético/administración & dosificación , Ácido Aminooxiacético/farmacología , Animales , Temperatura Corporal/efectos de los fármacos , Hipoxia/complicaciones , Masculino , Microinyecciones , Ratas , Ratas Endogámicas SHR , Núcleo Solitario/metabolismo , Núcleo Solitario/fisiopatología , Sulfuros/administración & dosificación , Sulfuros/farmacologíaRESUMEN
As a gas signaling molecule, endogenous hydrogen sulfide (H2S) plays a crucial role in the plant stress response. However, the role of H2S in the response to organic pollutants specifically has not been studied. Here, the effects of H2S addition on soybean (Glycine max) seedlings tolerance of 1,4-dichlorobenzene (1,4-DCB) were investigated. Under 1,4-DCB stress, the growth of soybean seedlings roots and stems was inhibited, while L-/D-cysteine desulfhydrase (LCD/DCD) activity was induced and endogenous H2S increased. When applied jointly with sodium hydrosulfide (NaHS), a H2S donor, root growth inhibition was effectively alleviated. Pre-treatment of seedlings with 0.4mmol L-1 NaHS reduced the malondialdehyde (MDA) and reactived oxygen species (ROS) content, mitigating root cell toxicity significantly. Further experiments confirmed that NaHS enhanced soybean seedlings peroxidase (POD) and superoxide dismutase (SOD) enzyme activities. In contrast, these effects were reversed by hypotaurine (HT), a H2S scavenger. Therefore, H2S alleviated 1,4-DCB toxicity in soybean seedlings by regulating antioxidant enzyme activity to reduce cell oxidative damage.(AU)
Tal como uma molécula de sinal de gás, sulfureto de hidrogenio endógena (H2S) desempenha um papel crucial na resposta ao stress das plantas. Mas não foi relatado o papel de H2S em plantas poluentes orgânicos stress. Este estudo sobre a variação de H2S envolvido em plântulas de soja tolerância 1,4-Diclorobenzeno foi investigada. Os resultados mostraram sob o 1,4-diclorobenzeno stress, que o crescimento da soja (Glycine max) de raiz de mudas e caule foram inibidas, L- / D-cisteína desulfhydrase (LCD / DCD) atividades enzimáticas foram empossados, em seguida, H2S endógeno aumentado. Quando aplicado com hidrossulfureto de sódio (NaSH), um doador de H2S, raiz de plântulas de soja, a inibição do crescimento pode ser melhorada. Tratamentos prévios com 0,4mmol L-1 NaHS, malondialdeído (MDA) e espécies de oxigênio reactivas conteúdo (ROS) foi reduzida, em seguida, a toxicidade celular da raiz foi reduzida significativamente. Outros experimentos confirmaram que NaSH melhorou a peroxidase de plântulas de soja (POD), superóxido dismutase (SOD) atividades enzimáticas. Em contraste, estes efeitos foram revertidos por hypotaurine (HT), um eliminador de H2S. Então H2S pode aliviar toxicidade 1,4-diclorobenzeno em plântulas de soja por meio da regulamentação das atividades de enzimas antioxidantes para manter a integridade da estrutura celular.(AU)
Asunto(s)
Glycine max/efectos de los fármacos , Glycine max/toxicidad , Sulfuros/administración & dosificación , Clorobencenos/administración & dosificación , Estrés Oxidativo/efectos de los fármacosRESUMEN
The generation of singlet oxygen (SO) in the presence of specific photosensitizers (PSs) or semiconductor quantum dots (QDs) and its application in photodynamic therapy (PDT) is of great interest to develop cancer therapies with no need of surgery, chemotherapy, and/or radiotherapy. This work was focused on the identification of the main factors leading to the enhancement of SO production using Rose Bengal (RB), and Methylene Blue (MB) as PS species in organic and aqueous mediums. Subsequently, the capacity of zinc oxide (ZnO), zinc sulfide (ZnS), and ZnO/ZnS core-shell QDs as well as manganese (Mn(+2)) doped ZnO and ZnS nanoparticles (NPs) as potential PS was also investigated. Many variable parameters such as type of quencher, PSs, NPs, as well as its different concentrations, light source, excitation wavelength, reaction time, distance from light source, and nature of solvent were used. The degradation kinetics of the quenchers generated by SO species and the corresponding quantum yields were determined by monitoring the photo-oxidation of the chemical quencher and measuring its disappearance by fluorometry and spectrophotometry in the presence of NPs. Small intracellular changes of SO induced by these metal Zn (zinc) NPs and PDT could execute and accelerate deadly programs in these leukemic cells, providing in this way an innovative modality of treatment. In order to perform further more specific in vitro cytotoxic studies on B-chronic lymphocytic leukemia cells exposed to Zn NPs and PDT, we needed first to measure and ascertain those possible intracellular SO variations generated by this type of treatment; for this purpose, we have also developed and tested a novel method first described by us.
Asunto(s)
Linfocitos B/efectos de los fármacos , Linfocitos B/metabolismo , Oxígeno Singlete/metabolismo , Células Cultivadas , Humanos , Luz , Manganeso/administración & dosificación , Nanopartículas/administración & dosificación , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/administración & dosificación , Puntos Cuánticos/administración & dosificación , Sulfuros/administración & dosificación , Compuestos de Zinc/administración & dosificación , Óxido de Zinc/administración & dosificaciónRESUMEN
OBJECTIVE: Oral myiasis is a rare infection for which treatment protocol has not yet been established. This article presents 2 cases treated with a combination of topical application of sulfuric ether and surgery. The reasons for the use of surgical therapy, as well as the possible advantages and disadvantages of drug-based treatments, are discussed. CASE REPORT: Two cases of oral myiasis are described, the first being observed in a 9-year-old child with hypotonic cerebral palsy, and the second in a 52-year-old adult, alcohol-dependent, both showing infection in the gingival sulcus. Both cases were successfully treated in a process that involved topical application of sulfuric ether, mechanical removal of larvae, and surgical debridement. CONCLUSIONS: Oral myiasis can be treated effectively with surgery after topical application of sulfuric ether. The use of drugs may suggest a therapeutic alternative, but still requires further study and experience to be implemented, especially in individuals with neurological disorders.
Asunto(s)
Enfermedades de las Encías/parasitología , Miasis/cirugía , Administración Tópica , Alcoholismo/complicaciones , Animales , Parálisis Cerebral/complicaciones , Niño , Desbridamiento , Humanos , Larva/efectos de los fármacos , Masculino , Persona de Mediana Edad , Miasis/tratamiento farmacológico , Sulfuros/administración & dosificación , Sulfuros/uso terapéuticoRESUMEN
Unsymmetrical dichalcogenides, a class of organoselenium compounds, were screened for antioxidant activity in rat brain homogenates in vitro. Unsymmetrical dichalcogenides (1-3) were tested against lipid peroxidation induced by sodium nitroprusside (SNP) or malonate, and reactive species (RS) production induced by sodium azide in rat brain homogenates. Compounds 1 (without a substituent at the phenyl group), 2 (chloro substituent at the phenyl group bounded to the sulfur atom) and 3 (chloro substituent at the phenyl group bounded to the selenium atom) protected against lipid peroxidation induced by SNP. The IC50 values followed the order 3<2<1. Lipid peroxidation induced by malonate was also reduced by dichalcogenides 1, 2 and 3. The IC50 values were 3Asunto(s)
Antioxidantes/farmacología
, Encéfalo/efectos de los fármacos
, Encéfalo/metabolismo
, Compuestos de Organoselenio/farmacología
, Estrés Oxidativo/efectos de los fármacos
, Sulfuros/farmacología
, Administración Oral
, Animales
, Antioxidantes/administración & dosificación
, Antioxidantes/química
, Encéfalo/enzimología
, Modelos Animales de Enfermedad
, Relación Dosis-Respuesta a Droga
, Activación Enzimática/efectos de los fármacos
, Glutatión Reductasa/metabolismo
, Glutatión Transferasa/metabolismo
, Inyecciones Intraventriculares
, Peroxidación de Lípido/efectos de los fármacos
, Masculino
, Malonatos
, Ratones
, Estructura Molecular
, Nitroprusiato
, Compuestos de Organoselenio/administración & dosificación
, Compuestos de Organoselenio/química
, Ratas
, Ratas Wistar
, Especies Reactivas de Oxígeno/metabolismo
, Azida Sódica
, Sulfuros/administración & dosificación
, Sulfuros/química
RESUMEN
Effective medications to treat acne sometimes become unavailable in certain countries, either for economic reasons or for shortage of them in the pharmaceutical market. The purpose of this report is to review a series of drugs of topical and systemic use; some old and some new. The topical group includes agents such as sulfur, salicylic acid and the alpha-hydroxy acids, while the systemic group includes diaminodiphenylsulfone, clofazimine, ibuprofen and others. Some presumably useful physical methodologies and the recent findings in phototherapy, particularly the properties of blue light and blue-red light, are also reviewed. Finally, we report on the results obtained from the combined use of isotretinoin and methylprednisone in severe inflammatory acne, to prevent a possible triggering of the 'pseudo' acne fulminans.