RESUMEN
Taking into account the memory-enhancing properties of 2-phenylethynyl-butyltellurium (PEBT) and the constant search for drugs that improve cognitive performance, the present study was designed to investigate the effect of PEBT on cognitive impairment induced by scopolamine in mice. PEBT (10 mg/kg, gavage) was administered to mice 1 h before the probe trial in the Morris water maze task. Memory impairment was induced by scopolamine (1 mg/kg, intraperitoneally) 30 min before the probe trial. PEBT significantly ameliorated the scopolamine-induced impairment of long-term memory, as indicated by a decrease in escape latency and an increase in the number of crossings of the platform location when compared with the amnesic mice. To evaluate the effect of PEBT on different phases of memory (acquisition, consolidation, and retrieval) impaired by scopolamine, the step-down inhibitory avoidance task was used. Scopolamine was administered 30 min before training (acquisition), test (retrieval), or immediately after training (consolidation). PEBT, administered 30 min before scopolamine, increased step-down latency in memory-impaired mice, improving the consolidation and retrieval stages, but not acquisition. No significant alterations in locomotor or exploratory behaviors were found in animals treated with PEBT and/or scopolamine. PEBT improved memory deficits during consolidation and retrieval induced by scopolamine.
Asunto(s)
Antagonistas Colinérgicos/toxicidad , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/tratamiento farmacológico , Compuestos Organometálicos/uso terapéutico , Escopolamina/toxicidad , Análisis de Varianza , Animales , Reacción de Prevención/efectos de los fármacos , Isótopos de Carbono , Modelos Animales de Enfermedad , Conducta Exploratoria/efectos de los fármacos , Inhibición Psicológica , Espectroscopía de Resonancia Magnética , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Ratones , Actividad Motora/efectos de los fármacos , Tiempo de Reacción/efectos de los fármacos , TritioRESUMEN
The aim of this study was to investigate the in vitro antioxidant activity of 2,2'-dipyridyl diselenide (e) by comparing this effect with m-trifluoromethyl-diphenyl diselenide (a), p-fluor-diphenyl diselenide (b), p-chloro-diphenyl diselenide (c), and p-methoxyl-diphenyl diselenide (d) in rat liver homogenate. We also investigated if the mechanisms involved in the antioxidant property of 2,2'-dipyridyl diselenide are the same that of other diselenides. Thiobarbituric acid reactive substances (TBARS) and protein carbonyl (PC) levels were determined in rat liver homogenate, as indicators of antioxidant activity. Dehydroascorbate (DHA) reductase- and glutathione S-transferase (GST)-like activities, 2,2'-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical-scavenging activities and the protection against the oxidation of Fe(2+) were determined to better understand the antioxidant property of compounds. δ-Aminolevulinic dehydratase (δ-ALA-D) activity was also carried out in rat liver homogenates, as a toxicological parameter. Compound e showed the highest potency in reducing TBARS (order of IC(50) values: e < b ≤ a < d ≤ c) and PC (order of IC(50) values: e < c ≤ b ≤ a < d) levels and lower potency in inhibiting δ-ALA-D activity than other diselenides. Compound e at all concentrations tested had no enzyme-mimetic property, but had radical-scavenging activity (≥5 µM) and protected against the oxidation of Fe(2+) (50 µM); while compounds a-d showed GST and DHA-mimetic activities and protected against the oxidation of Fe(2+), but had not radical-scavenging activities. This study indicates that (i) 2,2'-dipyridyl diselenide (e) had better in vitro antioxidant effect than other diselenides and lower inhibitory effect on δ-ALA-D activity, (ii) the presence of pyridine ring is responsible for the best antioxidant effect of this compound, and (iii) 2,2'-dipyridyl diselenide acts by different mechanisms of other diselenides.
Asunto(s)
2,2'-Dipiridil/análogos & derivados , Antioxidantes/farmacología , Compuestos de Organoselenio/farmacología , 2,2'-Dipiridil/química , 2,2'-Dipiridil/farmacología , Animales , Antioxidantes/química , Ácido Ascórbico/química , Derivados del Benceno/química , Derivados del Benceno/farmacología , Ácido Deshidroascórbico/química , Compuestos Ferrosos/química , Glutatión/química , Glutatión Transferasa/química , Peroxidación de Lípido , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Compuestos de Organoselenio/química , Compuestos de Organosilicio/química , Compuestos de Organosilicio/farmacología , Oxidación-Reducción , Oxidorreductasas/química , Porfobilinógeno Sintasa/antagonistas & inhibidores , Porfobilinógeno Sintasa/metabolismo , Carbonilación Proteica , Ratas , Ratas Wistar , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Extractos de TejidosRESUMEN
The present study investigated the effect of ebselen (EB) against hyperglycemia induced by the organophosphate (OPI) diazinon (DI) in rats. The insulin-mimetic properties of EB were investigated in vitro with the aim of better understanding the hypoglycemic effect of this compound. The protective effect of EB against pancreatic and hepatic damage caused by DI in rats was also appraised. In the in vivo experiments, rats were pre-treated with a single injection of EB (50mg/kg, intraperitoneal, i.p.). Afterward, animals were treated with a single injection of DI (200 mg/kg, i.p.). The parameters indicative of pancreatic and hepatic damage such as, serum amylase, lipase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) activities as well as serum glucose levels, hepatic glycogen content and glucose-6-phosphatase (G6Pase) activity were determined. EB pre-treatment was effective in reducing serum amylase, lipase, AST, ALT, ALP, and LDH activities, protecting against pancreatic and hepatic damage. EB reduced hyperglycemia and increased hepatic glycogen content in animals exposed to DI. In the in vitro assays, EB (150 µM) or insulin (IN 10 µM, positive control) was incubated with either skeletal muscle or hepatic tissue with the aim of measuring glucose uptake, glycogen synthesis and glycogen breakdown. EB increased the glucose uptake in skeletal muscle, stimulated hepatic glycogen synthesis and inhibited glycogen breakdown in a similar way to IN. In conclusion, EB, possibly through its insulin-mimetic action, protected against pancreatic and hepatic damage caused by DI in rats.
Asunto(s)
Azoles/farmacología , Diazinón/toxicidad , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/metabolismo , Hígado/efectos de los fármacos , Compuestos de Organoselenio/farmacología , Acetilcolinesterasa/metabolismo , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Animales , Aspartato Aminotransferasas/sangre , Eritrocitos/efectos de los fármacos , Eritrocitos/enzimología , Glucosa-6-Fosfatasa/metabolismo , Hiperglucemia/inducido químicamente , Isoindoles , L-Lactato Deshidrogenasa/sangre , Hígado/metabolismo , Masculino , Imitación Molecular , Páncreas/efectos de los fármacos , Páncreas/metabolismo , Ratas , Ratas WistarRESUMEN
Here we present our results in palladium cross-coupling reaction of aryl boronic acids with 4-iodo-2,3-dihydroselenophene derivatives. The cross-coupled products were obtained in satisfactory yields. A dehydrogenation of 4,5-diphenyl-2,3-dihydroselenophene was activated by DDQ and the 2,3-diarylselenophene was obtained in good yield. Regarding the antioxidant activity, the selenophene derivative 3a was effective in counteracting lipid and protein oxidation as well as scavenging ABTS radical. The findings of the present study indicate that 3a is a prototype for future drug development programs to treat disorders mediated by reactive oxygen species.
Asunto(s)
Antioxidantes/química , Compuestos de Organoselenio/química , Animales , Antioxidantes/farmacología , Reactivos de Enlaces Cruzados/química , Masculino , Estructura Molecular , Compuestos de Organoselenio/farmacología , Ratas , Ratas Wistar , Relación Estructura-ActividadRESUMEN
The antidepressant-like effect of repeated administration of diphenyl diselenide (PhSe)2 in rats exposed to malathion is reported. The role of Na+K+ ATPase, acetylcholinesterase (AChE) and monoamine oxidase (MAO) activities and oxidative stress in antidepressant behavior were investigated in cerebral cortex of rats. Rats were exposed once a day for 3 consecutive days to malathion (50mg/kg, intraperitoneal) and (PhSe)2 (50mg/kg, oral). To investigate the antidepressant-like behavior rats were submitted to the forced swimming test (FST) and open-field test (OFT). Thiobarbituric acid reactive species (TBARS) levels, enzymatic and non-enzymatic antioxidant defenses were carried out in cerebral cortex of rats. The results confirmed that malathion increased immobility time in the FST without altering the locomotor performance in the OFT. Treatment with (PhSe)2 ameliorated performance in the FST without altering the crossing numbers in the OFT. The inhibition of Na+K+ ATPase activity caused by malathion was prevented by treatment with (PhSe)2. Exposure to malathion did not alter parameters of oxidative stress as well as AChE and MAO activities in cerebral cortex of rats. In conclusion, (PhSe)2 exerted antidepressant-like effect in rats exposed to malathion. Na+K+ ATPase activity is, at least in part, involved in (PhSe)2 antidepressant-like behavior.