Diphenyl diselenide elicits antidepressant-like activity in rats exposed to monosodium glutamate: A contribution of serotonin uptake and Na(+), K(+)-ATPase activity.

Depression is a disorder with symptoms manifested at the psychological, behavioral and physiological levels. Monosodium glutamate (MSG) is the most widely used additive in the food industry; however, some adverse effects induced by this additive have been demonstrated in experimental animals and humans, including functional and behavioral alterations. The aim of this study was to investigate the possible antidepressant-like effect of diphenyl diselenide (PhSe)2, an organoselenium compound with pharmacological properties already documented, in the depressive-like behavior induced by MSG in rats. Male and female newborn Wistar rats were divided in control and MSG groups, which received, respectively, a daily subcutaneous injection of saline (0.9%) or MSG (4g/kg/day) from the 1st to 5th postnatal day. At 60th day of life, animals received (PhSe)2 (10mg/kg, intragastrically) 25min before spontaneous locomotor and forced swimming tests (FST). The cerebral cortices of rats were removed to determine [(3)H] serotonin (5-HT) uptake and Na(+), K(+)-ATPase activity. A single administration of (PhSe)2 was effective against locomotor hyperactivity caused by MSG in rats. (PhSe)2 treatment protected against the increase in the immobility time and a decrease in the latency for the first episode of immobility in the FST induced by MSG. Furthermore, (PhSe)2 reduced the [(3)H] 5-HT uptake and restored Na(+), K(+)-ATPase activity altered by MSG. In the present study a single administration of (PhSe)2 elicited an antidepressant-like effect and decrease the synaptosomal [(3)H] 5-HT uptake and an increase in the Na(+), K(+)-ATPase activity in MSG-treated rats.

Homeostatic effect of p-chloro-diphenyl diselenide on glucose metabolism and mitochondrial function alterations induced by monosodium glutamate administration to rats.

The metabolic syndrome is a group of metabolic alterations considered a worldwide public health problem. Organic selenium compounds have been reported to have many different pharmacological actions, such as anti-hypercholesterolemic and anti-hyperglycemic. The aim of this study was to evaluate the effect of p-chloro-diphenyl diselenide (p-ClPhSe)2, an organic selenium compound, in a model of obesity induced by monosodium glutamate (MSG) administration in rats. The rats were treated during the first ten postnatal days with MSG and received (p-ClPhSe)2 (10 mg/kg, intragastrically) from 45th to 51 th postnatal day. Glucose, lipid and lactate levels were determined in plasma of rats. Glycogen levels and activities of tyrosine aminotransferase, hexokinase, citrate synthase and glucose-6-phosphatase (G-6-Pase) were determined in livers of rats. Renal G-6-Pase activity was also determined. The purine content [Adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate] and mitochondrial functionality in the liver were also investigated. p-(ClPhSe)2 did not alter the reduction in growth performance and in the body weight caused by MSG but reduced epididymal fat deposition of rats. p-(ClPhSe)2 restored glycemia, triglycerides, cholesterol and lactate levels as well as the glucose metabolism altered in rats treated with MSG. p-(ClPhSe)2 restored hepatic mitochondrial dysfunction and the decrease in citrate synthase activity and ATP and ADP levels caused by MSG in rats. In summary, (p-ClPhSe)2 had homeostatic effects on glucose metabolism and mitochondrial function alterations induced by MSG administration to rats.

Antinociceptive action of diphenyl diselenide in the nociception induced by neonatal administration of monosodium glutamate in rats.

Monosodium glutamate (MSG) is a neuroexcitatory amino acid commonly used as flavoring of foods. MSG neonatal administration to animals leads to behavioral and physiological disorders in adulthood, including increased pain sensitivity. This study aimed to investigate the effect of diphenyl diselenide (PhSe)2, an organoselenium compound with pharmacological properties already documented, on nociception induced by MSG. Newborn Wistar rats received 10 subcutaneous injections of MSG at a dose of 4.0g/kg or saline (once daily). At the 60th day of life, the rats were daily treated with (PhSe)2 (1mg/kg) or vehicle (canola oil) by the intragastric route for 7 days. The behavioral tests (locomotor activity, hot plate, tail-immersion and mechanical allodynia) were carried out. Ex vivo assays were performed in samples of hippocampus to determine Na(+), K(+)-ATPase and Ca(2+)-ATPase activities, cytokine levels and [(3)H]glutamate uptake. The results demonstrated that MSG increased nociception in the hot plate test and in the mechanical allodynia stimulated by Von-Frey hair but did not alter the tail immersion test. (PhSe)2 reversed all nociceptive behaviors altered by MSG. MSG caused an increase in Na(+),K(+)-ATPase and Ca(2+)-ATPase activities and in pro-inflammatory cytokine levels and a decrease in the anti-inflammatory cytokine and in the [(3)H]glutamate uptake. (PhSe)2 was effective in reversing all alterations caused by MSG. The results indicate that (PhSe)2 had a potential antinociceptive and anti-inflammatory action in the MSG model.

Involvement of the serotonergic system in the anxiolytic-like effect of 2-phenylethynyl butyltellurium in mice.

Anxiety is a serious disorder with symptoms manifested at the psychological, behavioral, and physiological levels, accompanied by alterations in the serotonergic system and monoaminergic signaling. In this study, the anxiolytic-like effect of 2-phenylethynyl butyltellurium (PEBT), in three well-consolidated anxiety mouse models (light-dark test, novelty suppressed-feeding, elevated plus-maze), was investigated. The involvement of the serotonergic system, synaptosomal [(3)H] serotonin (5-HT) uptake and monoamine oxidase (MAO A and B) activities on cerebral cortices of mice, was examined. Mice received PEBT (1mg/kg, by intragastric route, i.g.) or canola oil (10 ml/kg, i.g.) 30 min before behavioral tests. The results showed that PEBT was effective in increasing the time spent by mice in the illuminated side on the light-dark box and in the open arms on the elevated plus-maze. PEBT decreased the latency to begin eating on the novelty suppressed-feeding test, indicating an anxiolytic-like effect of PEBT. Furthermore, PEBT reduced [(3)H] 5-HT uptake and selectively inhibited MAO-A activity in cerebral cortex, suggesting the involvement of the serotonergic system in the mechanism of action of this tellurium compound.

Caffeine suppresses exercise-enhanced long-term and location memory in middle-aged rats: Involvement of hippocampal Akt and CREB signaling.

The cognitive function decline is closely related with brain changes generated by age. The ability of caffeine and exercise to prevent memory impairment has been reported in animal models and humans. The purpose of the present study was to investigate whether swimming exercise and caffeine administration enhance memory in middle-aged Wistar rats. Male Wistar rats (18months) received caffeine at a dose of 30mg/kg, 5days per week by a period of 4weeks. Animals were subjected to swimming training with a workload (3% of body weight, 20min per day for 4weeks). After 4weeks, the object recognition test (ORT) and the object location test (OLT) were performed. The results of this study demonstrated that caffeine suppressed exercise-enhanced long-term (ORT) and spatial (OLT) memory in middle-aged and this effect may be related to a decrease in hippocampal p-CREB signaling. This study also provided evidence that the effects of this protocol on memory were not accompanied by alterations in the levels of activated Akt. The [(3)H] glutamate uptake was reduced in hippocampus of rats administered with caffeine and submitted to swimming protocol.

Monosodium glutamate, a food additive, induces depressive-like and anxiogenic-like behaviors in young rats.

UNLABELLED: Monosodium glutamate (MSG) has been the target of research due to its toxicological effects. AIMS: We investigated the depressive- and anxiogenic-like behaviors in rats exposed to neonatal subcutaneous injection of MSG. The involvement of the serotonergic system, by measuring [(3)H] serotonin (5-HT) uptake in cerebral cortices, and the hypothalamic pituitary adrenal (HPA) axis, by determining serum adrenocorticotropic hormone (ACTH) and corticosterone levels, was also examined. MATERIALS AND METHODS: Male and female newborn Wistar rats were divided into control and MSG groups, which received, respectively, a daily subcutaneous injection of saline (0.9%) or MSG (4 g/kg/day) from the 1st to 5th postnatal day. The behavioral tests [spontaneous locomotor activity, contextual fear conditioning, and forced swimming test (FST)] were performed from the 60th to 64th postnatal day. MSG-treated animals showed alteration in the spontaneous locomotor activity, an increase in the number of fecal pellets and the number of animal's vocalizations and urine occurrence, and a decrease in the grooming time. KEY FINDINGS: The MSG exposure increased the immobility time in the FST and the freezing reaction in the contextual fear conditioning. Additionally, MSG treatment increased the [(3)H]5-HT uptake in the cerebral cortices of rats and induced a deregulation of HPA axis function (by increasing serum ACTH and corticosterone levels). SIGNIFICANCE: In conclusion MSG-treated rats are more susceptible to develop anxiogenic- and depressive-like behaviors, which could be related to a dysfunction in the serotonergic system.

Moderate swimming exercise and caffeine supplementation reduce the levels of inflammatory cytokines without causing oxidative stress in tissues of middle-aged rats.

The levels of circulatory inflammatory markers, including interleukin (IL) IL-1ß, IL-6, tumor necrosis factor-α (TNF-α) and interferon (INF-γ), are known to increase associated to aging. Caffeine has been reported to produce many beneficial effects for health. Exercise is considered to be a safe medicine to attenuate inflammation and cellular senescence. The purpose of the present study was to investigate the effects of a moderate-intensity swimming exercise (3 % of body weight, 20 min per day, 4 weeks) and sub-chronic supplementation with caffeine (30 mg/kg, 4 weeks) on the serum cytokine levels in middle-aged (18 months) Wistar rats. The effects of swimming exercise and caffeine on oxidative stress in muscle and liver of middle-aged rats were also investigated. The two-way ANOVA of pro-inflammatory cytokine levels demonstrated a significant exercise x caffeine interaction for IL-1ß (F (1, 16) = 9.5772; p = 0.0069), IL-6 (F (1, 16) = 8.0463; p = 0.0119) and INF-γ (F (1, 16) = 15.078; p = 0.0013). The two-way ANOVA of TNF-α levels revealed a significant exercise × caffeine interaction (F (1, 16) = 9.6881; p = 0.00670). Swimming exercise and caffeine supplementation increased the ratio of reduced glutathione/oxidized glutathione in the rat liver and gastrocnemius muscle. Hepatic and renal markers of damage were not modified. In conclusion, a moderate-intensity swimming exercise protocol and caffeine supplementation induced positive adaptations in modulating cytokine levels without causing oxidative stress in muscle and liver of middle-aged rats.

Application of copper(I) iodide/diorganoyl dichalcogenides to the synthesis of 4-organochalcogen isoquinolines by regioselective C-N and C-chalcogen bond formation.

A copper-catalyzed cyclization of (ortho-alkynyl)benzaldimines with diorganoyl dichalcogenides allowed the synthesis of 4-organochalcogen isoquinolines, whereas the presence of base in the reaction medium inhibited the product formation producing the undesirable isoquinoline without the organochalcogen atom at the 4-position. The cyclization reaction was carried out by using CuI (20 %) as a catalyst with diorganoyl dichalcogenides (1.5 equiv) in the presence of DMF at 100 °C. Furthermore, the reaction did not require an argon atmosphere and was carried out in an open flask. The cyclization reaction tolerated a variety of functional groups both in ortho-alkynylbenzaldimines and diorganoyl dichalcogenides, such as trifluoromethyl, chloro, fluorine, and methoxyl, to give the six-membered heterocyclic ring exclusively through a 6-endo-dig cyclization process. The organochalcogen group present at the 4-position of the isoquinoline ring was further subjected to a selective chalcogen-lithium exchange reaction followed by the addition of aldehydes to afford the desired secondary alcohols in good yields. The obtained isoquinolines also proved to be suitable substrates for the Suzuki and Sonogashira coupling conditions affording the corresponding products through C-C bond formation.

Diphenyl diselenide ameliorates cognitive deficits induced by a model of menopause in rats.

Ovarian hormone loss contributes to cognitive decline in postmenopausal women. Studies have demonstrated a positive role of the level of the element selenium in cognitive performance. The present study investigated the effects of the synthetic organoselenium compound diphenyl diselenide (PhSe)2 on cognitive functions in ovariectomized rats. Ninety-day-old female Wistar rats were subjected to ovariectomy (OVX) or Sham operation. One week after surgery, rats were orally treated with (PhSe)2 (5 mg/kg, per oral route) or vehicle once a day for 30 days. Next, the rats were evaluated in behavioral tests [Morris water maze (MWM) and open-field tests] and biochemical [cerebral acetylcholinesterase (AChE)] analyses were carried out. In MWM probe trial, (PhSe)2 decreased the latency to reach the platform location and increased the number of crossings over the platform location, protecting against cognitive impairment induced by OVX. Furthermore, (PhSe)2 prevented the stimulation of AChE activity caused by OVX. In conclusion, the present study showed a cognition-enhancing effect of (PhSe)2 treatment for 30 days in ovariectomized rats in the MWM test, which could be related to its ability to prevent the stimulation of AChE activity caused by OVX in rats. These findings suggest that (PhSe)2 might have a promising role in preventing the cognitive decline related to menopause.

Copper iodide-catalyzed cyclization of (Z)-chalcogenoenynes.

We present here our results of the efficient copper-catalyzed cyclizations of chalcogenoenynes and establish a route to obtain 3-substituted chalcogenophenes in good to excellent yields. In addition, the obtained chalcogenophenes were readily transformed to more complex products using the palladium-catalyzed cross-coupling reactions with boronic acids to give Suzuki-type products in good yields.