Effects of organic and inorganic selenium supplementation on frozen-thawed ram semen at two cooling periods.

The aim of this study was to evaluate the effects of different selenium compounds on the sperm quality of cryopreserved ram semen. Ejaculates from four rams, collected using an artificial vagina heated to 38 °C, were individually evaluated. The approved ejaculates were pooled and diluted (1:1 v:v) in Tris-egg yolk extender (20%, v/v) and separated into two control groups, one cooled for 2 h and the other for 4 h. The pooled ejaculates at the two cooling periods were supplemented with two doses (0.5 and 1 µg/mL) of organic selenium (ORG), and inorganic selenium (SeNa), each. The samples were packed in 0.25 ml straws, at a concentration of 400 × 106 sperms/mL and stored in liquid nitrogen. The straws were thawed in a water bath at 37 °C for 20 s, and the samples were subjected to sperm kinetics evaluation by Computer Assisted Semen Analysis software. Sperm membrane integrity, acrosome morphology, and mitochondrial potential were assessed. In addition, oxidative stress markers reactive oxygen species (ROS), ferric reducing antioxidant power (FRAP), thiobarbituric acid reactive species (TBARS), and glutathione peroxidase (GPx) enzyme activity) were also evaluated. No significant improvement was observed in the ram semen quality at the two cooling times. Supplementation of the freezing extender with 0.5 µg/mL ORG, subjected to 4 h cooling period, increased the sperm motility when compared with the control group at the same cooling time. In addition, the 0.5 µg/mL SeNa group, under the 2 h cooling period, showed an increase in sperm motility when compared to the control group at the same cooling period. Considering the importance of sperm motility as a fertility parameter, our study indicates that supplementation with ORG and SeNa can help improve the total motility of the cryopreserved ram semen.

Photoactive glycoconjugates with a very large Stokes shift: synthesis, photophysics, and copper(II) and BSA sensing.

This study presents the synthesis of novel glycoconjugates by connecting benzazole and carbohydrate units with a 1,2,3-triazole linker. A simple synthetic route employing a copper(I) catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) was utilized. The synthesized compounds exhibit excited-state intramolecular proton transfer (ESIPT), resulting in longer wavelength emission with a significantly large Stokes shift (∼10 000 cm-1). These compounds show potential as chemical sensors due to their ability to detect Cu2+ ions, causing a decrease in fluorescence emission (turn-off effect). Additionally, they demonstrate strong interaction with proteins, exemplified by their interaction with bovine serum albumin (BSA) as a model protein.

Protective effects of octylseleno-xylofuranoside in a streptozotocin-induced mouse model of Alzheimer's disease.

Octylseleno-xylofuranoside (OSX) is an organic selenium compound which has previously shown antioxidant and antidepressant-like activities, trough the modulation of monoaminergic system and synaptic plasticity pathways. Since recent studies have suggested Major Depressive Disorder (MDD) as a potential risk factor or condition that precedes and correlates with Alzheimer's Disease (AD), this study aimed to evaluate the protective effects of OSX in an AD mouse model induced by intracerebroventricular injection of streptozotocin (STZ). To address this protective effect, mice were pre-treated with intragastrical OSX (0.1 mg/kg) or vehicle for 20 days. After the pre-treatment, mice were submitted to two alternated intracerebroventricular infusions of STZ (days 21 and 23) or saline. 15 days after the last STZ injection, cognitive and memory skills of the treated mice were evaluated on object recognition test, Y-maze, stepdown passive avoidance and social recognition paradigms. Added to that, measurements of oxidative stress markers and gene expression were evaluated in brain samples of the same mice groups. Mice pre-treatment with OSX protected mice from cognitive and memory decline elicited by STZ. This effect was attributed to the prevention of lipid peroxidation and modulation of acetylcholinesterase and monoamine oxidase activities in cerebral cortices and hippocampi by OSX treatment. Furthermore, OSX treatment demonstrated reduction of amyloidogenic pathway genes expression when compared to the control groups. Besides that, OSX treatment showed no hepatic and renal toxicity in the protocol used for treatment. Considering the antidepressant-like effect of OSX, together with the ability to prevent memory and cognitive impairment, this new compound may be an interesting strategy for targeting the comorbidity between MDD and AD, in a multitarget drug paradigm.

Glycoconjugates Based on Supramolecular Tröger's Base Scaffold: Synthesis, Photophysics, Docking, and BSA Association Study.

This study presents new Tröger's bases bearing glycosyl moieties obtained from a copper-catalyzed azide-alkyne cycloaddition reaction. The Tröger's bases present absorption maxima close to 275 nm related to fully spin and symmetry-allowed electronic transitions. The main fluorescence emission located at 350 nm was observed with no influence on the glycosyl moieties. Furthermore, protein detection studies have been performed using bovine serum albumin (BSA) as a model protein, and results have shown a strong interaction between some of the compounds through a static fluorescence suppression mechanism related to the formation of a glycoconjugate-BSA complex favored by the glycosyl subunit. Moreover, docking was also studied for better understanding the suppression mechanism and indicated that the glycosyl and triazole moieties increase the affinity with BSA.

Synthesis of new lophine-carbohydrate hybrids as cholinesterase inhibitors: cytotoxicity evaluation and molecular modeling.

In this study, we synthesized nine novel hybrids derived from d-xylose, d-ribose, and d-galactose sugars connected by a methylene chain with lophine. The compounds were synthesized by a four-component reaction to afford the substituted imidazole moiety, followed by the displacement reaction between sugar derivatives with an appropriate N-alkylamino-lophine. All the compounds were found to be the potent and selective inhibitors of BuChE activity in mouse serum, with compound 9a (a d-galactose derivative) being the most potent inhibitor (IC50 = 0.17 µM). According to the molecular modeling results, all the compounds indicated that the lophine moiety existed at the bottom of the BuChE cavity and formed a T-stacking interaction with Trp231, a residue accessible exclusively in the BuChE cavity. Noteworthily, only one compound exhibited activity against AChE (8b; IC50 = 2.75 µM). Moreover, the in silico ADME predictions indicated that all the hybrids formulated in this study were drug-likely, orally available, and able to reach the CNS. Further, in vitro studies demonstrated that the two most potent compounds against BuChE (8b and 9a) had no cytotoxic effects in the Vero (kidney), HepG2 (hepatic), and C6 (astroglial) cell lines.

Proton-Transfer-Based Azides with Fluorescence Off-On Response for Detection of Hydrogen Sulfide: An Experimental, Theoretical, and Bioimaging Study.

This work describes the synthesis of photoactive proton transfer compounds based on the benzazolic core containing the azide group. The compounds present absorption in the UV region and fluorescence emission in the visible region of the spectra with large Stokes shift due to a phototautomerism in the excited state (ESIPT). The azide location on the benzazolic structure presented a noteworthy role on their photophysics, leading to fluorescence quenching. A photophysical study was performed in the presence of NaHS to evaluate their application as an H2S sensor. The methodology employed was the reduction of azides to amines using NaHS to mimic H2S, resulting in an off-on response fluorescence mechanism. The observed photophysical features were successfully used to explore the azides as fluorescent probes in biological media. In addition, DFT and TD-DFT calculations with the CAM-B3LYP/cc-pVDZ and CAM-B3LYP/jun-cc-pVTZ level, respectively, were performed in order to understand the photophysics features of azide derivatives, where the main interest was to investigate the fluorescence quenching experimentally observed in the azide derivatives.

Selenofuranoside improves long-term memory deficits in rats after exposure to monosodium glutamate: Involvement of Na+, K+-ATPase activity.

Monosodium glutamate (MSG) is the most widely used additive in the food industry; however, some adverse effects of this additive, including functional, learning, and behavioral alterations, have been observed in experimental animals and humans. Studies have shown learning and memory impairment in adult animals exposed to MSG. However, studies relating exposure to MSG to acetylcholinesterase (AChE) and Na+, K+-ATPase activities and memory damage are still scarce in the literature. The aim of the present study was to assess the possible protective effects of selenofuranoside, an organoselenium compound, against the impairment of long-term memory, Na+, K+-ATPase and AChE activities, and oxidative stress after MSG exposure in rats. MSG (2g/kg) and/or selenofuranoside (5mg/kg) were administered orally to 5-week-old male Wistar rats for 10days. On the 10th day, after the administration of last dose of the drug(s), the rats were subjected to behavioral tests: the open-field test and step-down passive avoidance task (SDPA). The blood, liver, kidney, cortex, and hippocampus were removed to determine the oxidative stress parameters, such as the levels of reactive species, lipid peroxidation, antioxidant enzyme activities, and endogenous nonenzymatic antioxidant content. Furthermore, the cortex and hippocampus were used to determine the Na+, K+-ATPase and AChE activities. The results demonstrate that the administration of MSG led to long-term memory impairment, as shown in the SDPA task, and also hippocampal and cortical Na+, K+-ATPase inhibition. There were no alterations in the AChE activity and oxidative stress parameters. Treatment with selenofuranoside attenuated memory impairment associated with MSG exposure by improving the hippocampal Na+, K+-ATPase activity.

Cadmium inhibits the ovary δ-aminolevulinate dehydratase activity in vitro and ex vivo: protective role of seleno-furanoside.

Cadmium (Cd) toxicity is a concern to the tobacco-smoking sub-population which includes millions of people worldwide. Although this metal may cause severe damage to embryos and the reproductive organs, the precise mechanisms underlying its toxicity remain unclear. In the present study, the Cd effect on ovary δ-aminolevulinate dehydratase (δ-ALA-D) activity was investigated in vitro and ex vivo. We observed that low concentrations of Cd inhibited cow ovary δ-ALA-D activity in vitro and the IC50 value obtained was 19.17 µM. Furthermore, the protective effect of a novel organic selenium compound (seleno-furanoside) in restoring enzyme activity was evaluated. Seleno-furanoside (10, 50, 100, 200, 400 and 1000 µM) did not reverse the Cd toxicity in bovine ovarian tissue in vitro. According to the in vitro reults, acute Cd exposure (2.5 and 5 mg kg(-1)) caused a significant inhibition in ovary δ-ALA-D activity in mice (around 27% and 34%, respectively). Therapy with seleno-furanoside (100 µmol kg(-1)) was able to restore enzyme activity. Thus, we demonstrated for the first time that δ-ALA-D activity from ovary is inhibited by Cd both in vitro and ex vivo. Additionally, seleno-furanoside therapy was effective in restoring ovarian enzyme activity inhibited by Cd exposure in mice, but it did not reverse the in vitro metal effect. This study detected a new toxicity marker of Cd toxicity on ovarian tissue as well as the beneficial effect of a new compound to manage the metal effect after acute exposure.