Swimming exercise and diphenyl diselenide-supplemented diet modulate cerebral cortical and striatal GABA uptake in aged rats.

Aging is characterized by several neurochemical modifications involving structural proteins and neurotransmitters. Exercise has been recognized as an enhancer of overall health; whereas, diphenyl diselenide (PhSe)2 has been reported to have antioxidant, anti-inflammatory, and neuroprotective effects in rodents. A combination of pharmacological and non-pharmacological interventions has been proposed to prevent the aging effects. This study aimed to determine the swimming exercise and (PhSe)2 dietary supplementation synergic effects on the [3H] γ-aminobutyric acid (GABA) uptake in aged rats. Male Wistar rats (24 months) received 1 ppm of (PhSe)2 supplemented in the standard chow for 4 weeks. Rats were subjected to swimming training (20 min per day for 4 weeks). After 4 weeks, the [3H]GABA uptake was determined in samples of cerebral cortex and striatum of rats. The results of the present study demonstrate that the association of (PhSe)2-supplemented diet and swimming exercise was effective against the decrease of cerebral cortical and striatal [3H]GABA uptake in aged rats. The association of (PhSe)2 dietary supplementation with swimming exercise modulated the GABA uptake in cerebral structures of aged rats.

A greener protocol for the synthesis of phosphorochalcogenoates: Antioxidant and free radical scavenging activities.

In this contribution, a metal- and base-free protocol has been developed for the synthesis of phosphorochalcogenoates (Se and Te) by using DMSO as solvent at 50 °C. A variety of phosphorochalcogenoates were prepared from diorganyl dichalcogenides and H-phosphonates, leading to the formation of a Chal-P(O) bond, in a rapid procedure with good to excellent yields. A full structural elucidation of products was accessed by 1D and 2D NMR, IR, CGMS, and HRMS analyses, and a stability evaluation of the phosphorochalcogenoates was performed for an effective operational description of this simple and feasible method. Typical 77Se{1H} (δSe = 866.0 ppm), 125Te{1H} (δTe = 422.0 ppm) and 31P{1H} (δP = -1.0, -13.0 and -15.0 ppm) NMR chemical shifts were imperative to confirm the byproducts, in which this stability study was also important to select some products for pharmacological screening. The phosphorochalcogenoates were screened in vitro and ex vivo tests for the antioxidant potential and free radical scavenging activity, as well as to investigation toxicity in mice through of the plasma levels of markers of renal and hepatic damage. The pharmacological screening of phosphorochalcogenoates indicated that compounds have antioxidant propriety in different assays and not changes plasma levels of markers of renal and hepatic damage, with excision of 3g compound that increased plasma creatinine levels and decreased plasma urea levels when compared to control group in the blood mice. Thus, these compounds can be promising synthetic antioxidants that provide protection against oxidative diseases.

Evaluation of antioxidant activity and toxicity of sulfur- or selenium-containing 4-(arylchalcogenyl)-1H-pyrazoles.

Pyrazoles represent a significant class of heterocyclic compounds that exhibit pharmacological properties. The present study aimed to investigate the antioxidant potential of pyrazol derivative compounds in brain of mice in vitro and the effect of pyrazol derivative compounds in the oxidative damage and toxicity parameters in mouse brain and plasma of mice. The compounds tested were 3,5-dimethyl-1-phenyl-4-(phenylselanyl)-1H-pyrazol (1a), 3,5-dimethyl-4-(phenylselanyl)-1H-pyrazole (2a), 4-((4-methoxyphenyl)selanyl)-3,5-dimethyl-1-phenyl-1H-pyrazole (3a), 4-((4-chlorophenyl)selanyl)-3,5-dimethyl-1-phenyl-1H-pyrazole (4a), 3,5-dimethyl-1-phenyl-4-(phenylthio)-1H-pyrazole (1b), 3,5-dimethyl-4-(phenylthio)-1H-pyrazole (2b), 4-((4-methoxyphenyl)thio)-3,5-dimethyl-1-phenyl-1H-pyrazole (3b), 4-((4-chlorophenyl)thio)-3,5-dimethyl-1-phenyl-1H-pyrazole (4b), and 3,5-dimethyl-1-phenyl-1H-pyrazole (1c). In vitro, 4-(arylcalcogenyl)-1H-pyrazoles, at low molecular range, reduced lipid peroxidation and reactive species in mouse brain homogenates. The compounds also presented ferric-reducing ability as well nitric oxide-scavenging activity. Especially compounds 1a, 1b, and 1c presented efficiency to 1,1-diphenyl-2-picryl-hydrazyl-scavenging activity. Compounds 1b and 1c presented 2,20 -azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)-scavenging activity. In vivo assays demonstrated that compounds 1a, 1b, and 1c (300 mg/kg, intragastric, a single administration) did not cause alteration in the of δ-aminolevulinic acid dehydratase activity, an enzyme that exhibits high sensibility to prooxidants situations, in the brain, liver, and kidney of mice. Compound 1c reduced per se the lipid peroxidation in liver and brain of mice. Toxicological assays demonstrate that compounds 1a, 1b, and 1c did not present toxicity in the aspartate aminotransferase, alanine aminotransferase, urea, and creatinine levels in the plasma. In conclusion, the results demonstrated the antioxidant action of pyrazol derivative compounds in in vitro assays. Furthermore, the results showed low toxicity of compounds in in vivo assays.

Depression-like behavior, hyperglycemia, oxidative stress, and neuroinflammation presented in diabetic mice are reversed by the administration of 1-methyl-3-(phenylselanyl)-1H-indole.

Oxidative stress and neuroinflammation are found both in diabetes mellitus and major depressive disorder (MDD). In addition to damage in peripheral organs, such as liver and kidney, diabetic patients have a higher risk of developing depression. In this sense, the objective of the present study was to characterize the antidepressant-like effect of a selenium-containing compound, the 1-methyl-3-(phenylselanyl)-1H-indole (MFSeI), in streptozotocin (STZ)-induced diabetic mice. STZ (200 mg/kg, i.p.) was used to induce diabetes mellitus type I, and after seven days, the administration of MFSeI (10 mg/kg, i.g.) was initiated and followed for the next 14 days. Twenty-four hours after the last administration of MFSeI, the behavioral tests were performed, followed by euthanasia. The treatment with MFSeI was able to reverse the hyperglycemia induced by STZ. MFSeI also decreased the plasma levels of biomarkers of liver and kidney damage. Importantly, MFSeI reversed the depression-like behavior induced by STZ in the tail suspension test and forced swimming test without promoting locomotor alterations. Furthermore, MFSeI reversed the increased levels of reactive species and lipid peroxidation in the prefrontal cortex (PFC), hippocampus (HC), liver, and kidney of STZ-treated mice. Treatment with MFSeI also decreased the expression of tumor necrosis factor-alpha, inducible nitric oxide synthase and indoleamine 2,3-dioxygenase, while increasing the expression of interleukin-10, insulin receptor substrate-1 and glucose transport-4 in the PFC and HC of mice. Taken together, the results indicate the effectiveness of MFSeI against depression-like behavior and central and peripheral complications caused by diabetes in mice.

Repeated administration of a selenium-containing indolyl compound attenuates behavioural alterations by streptozotocin through modulation of oxidative stress in mice.

Although the pathophysiology of major depression disorder (MDD) is still poorly understood, mounting evidence suggests that the brains of depressed patients are under oxidative stress, leading to depressive symptoms that may include anxiety and cognitive impairment. This study aimed to investigate if the seleno-organic compound 1-methyl-3-(phenylselanyl)-1H-indole (MFSeI) reverses the depression- and anxiogenic-like behaviour, cognitive impairment and oxidative stress induced by the intra-cerebroventricular injection of streptozotocin (STZ; 0.2 mg/4 µl/per mouse) in Swiss male mice. Twenty-four hours after the STZ injection, mice were treated with MFSeI (10 mg/kg, intra-gastrically), or vehicle solution, once daily for seven days. The behavioural tests were performed 30 min after the final MFSeI administration, followed by euthanasia and collection of the cerebral cortex and hippocampus. Administration of MFSeI reversed the depression- and anxiogenic-like behaviour and cognitive impairment induced by STZ, in mice. Neurochemical analyses demonstrated that MFSeI reversed the STZ-increased levels of reactive species, nitrite, lipid peroxidation and acetylcholinesterase activity in the cerebral cortex and hippocampus of mice. Moreover, a single administration of MFSeI (300 mg/kg, intra-gastrically) did not cause acute toxicity in Swiss male mice. Altogether, our data suggest that MFSeI exhibits antidepressant- and anxiolytic-like effects and improves the cognition of STZ-treated mice, without any toxicity.

Effectiveness of bis(phenylimidazoselenazolyl) diselenide on a mouse model of inflammatory nociception.

The injection of complete Freund's adjuvant (CFA) in the hindpaw of rodents induces tissue inflammation and nociceptive hypersensitivity. In addition, it has been reported that organoselenium compounds have antinociceptive properties in animal models. The purpose of this study was to investigate the potential antinociceptive effect of bis(phenylimidazoselenazolyl) diselenide (BPIS) in the inflammatory nociception model in mice and its possible mechanism of action. C57BL/6 mice received CFA intraplantar in right hindpaw and the inflammatory response was verified 24h after injection as well as the antinociceptive effect of BPIS. The CFA-induced mechanical allodynia was reversed by BPIS treatment (1mg/kg, p.o.) observed through the von Frey hair test. Additionally, L-arginine (600mg/kg; i.p.), administered before BPIS treatment, blocked its antinociceptive effect. Regarding myeloperoxidase activity, NOx and 3-nitrotyrosine levels, BPIS administration did not reverse alterations observed in the paw of animals injected with CFA. BPIS reversed the increase in spinal NOx content induced by CFA. In the spinal cord, it was also found that CFA induced an increase in malondialdehyde content and a decrease in glutamate uptake, and these alterations were reversed by BPIS. Moreover, BPIS treatment induced an increase in non-protein thiol levels in spinal cord of animals that received CFA injection. No alterations were found in glutathione peroxidase, reductase and S-transferase activities of experimental groups. The obtained data reinforce the relevance of BPIS as an antinociceptive agent as well as highlight the importance of the nitric oxide pathway in the spinal cord and its antioxidant potential for its mechanism of action.

Antiviral Action of Diphenyl Diselenide on Herpes Simplex Virus 2 Infection in Female BALB/c Mice.

Diphenyl diselenide, (PhSe)2 , is an organoselenium compound with pharmacological actions mostly related to antioxidant and anti-inflammatory properties. The study investigated its antiviral and virucidal actions against herpes simplex virus 2 (HSV-2) infection in vitro and in a vaginal infection model in mice. The plaque reduction assay indicated that (PhSe)2 showed virucidal and antiviral actions reducing infectivity in 70.8% and 47%, respectively. The antiviral action of (PhSe)2 against HSV-2 vaginal infection was performed by infecting mice (10(5) PFU/ml(-1) ) at day 6. The treatment with (PhSe)2 (5 mg/kg/day, intragastric [i.g.]) followed 5 days before and for more 5 days after infection. The extravaginal lesion score was evaluated from days 6 to 10. At day 11, animals were killed, and histological evaluation, determination of viral load, and TNF-α and IFN-γ levels were performed in supernatants of homogenized vaginal tissue. The levels of reactive species (RS), protein carbonyl, non-protein thiols (NPSH), nitrate/nitrite (NOx), and malondialdehyde (MDA), and the activities of myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) were determined. (PhSe)2 reduced the histological damage, extravaginal lesion scores, the viral load of vaginal tissue, and the activity of MPO, but increased the levels of TNF-α, IFN-γ. (PhSe)2 attenuated the increase of RS, MDA, NOx levels and the activity of GR caused by infection. (PhSe)2 also attenuated the reduction of NPSH content and the inhibition of CAT, SOD, and GPx activities. The antiviral action of (PhSe)2 against HSV-2 infection was related to its immunomodulatory, antioxidant, and anti-inflammatory properties. J. Cell. Biochem. 117: 1638-1648, 2016. © 2015 Wiley Periodicals, Inc.

2,2'-Dithienyl diselenide pro-oxidant activity accounts for antibacterial and antifungal activities.

The aim of this study was to explore if 2,2'-dithienyl diselenide (DTDS) pro-oxidant activity is related to its antibacterial and antifungal actions. The antimicrobial activity of DTDS against bacterial and fungal was investigated in the broth microdilution assay (3.02-387 µg/ml). Additionally, the survival curve of microorganisms in the presence of DTDS (12.09-193.5 µg/ml) was performed. The involvement of pro-oxidant activity in the DTDS antimicrobial action was investigated by supplementing the growth medium with 10 mM glutathione or ascorbic acid in the disk diffusion technique (0.64-640 µgDTDS/discs). The levels of reactive species (RS) induced by 25 mM DTDS were also determined. The results demonstrated that DTDS was effective in preventing the Gram-positive bacteria and Candida albicans growth. The minimum inhibitory concentration, twice and half concentrations of DTDS confirmed that the activity of compound was bactericidal for some microorganisms (Enterococcus faecalis, and Staphylococcus saprophyticus), bacteriostatic for Bacillus cereus and fungistatic for C. albicans. Antibacterial and antifungal actions of DTDS are related to the increase of reactive species levels. The presence of antioxidants in the growth medium avoided the DTDS antimicrobial action. In conclusion, DTDS showed promising antibacterial and antifungal actions, possibly related to its pro-oxidant activity.