Pharmacology of organoselenium compounds: Emphasis on puzzling mechanistic switching from their glutathione peroxidase mimic in vivo

Organoselenium compounds are a new class of emerging potent antioxidants. Basically, their rational design and synthesis was aimed at mimicking the native glutathione peroxidase enzyme in their reduction of hydroperoxides at the expense of the ubiquitous antioxidant, glutathione. In this review, emphasis was focused on the seemingly antagonistic mechanisms employed by organoseleniums under in vitro and in vivo conditions. Summarily, in vitro evidences clearly demonstrate that the pharmacological effect of organoseleniums strictly depends on their GPx mimic. However, these selenium based compounds evoke an increase in the level of endogenous thiols suggesting a possible switch in their glutathione peroxidase mimic under in vivo conditions. Apparently, this mechanistic switch is puzzling and requires concerted efforts to unravel

Thiol modifier effects of diphenyl diselenides: insight from experiment and DFT calculations

A combination of spectroscopic, chromatographic and computational approaches was employed to investigate the reaction of several diselenides of formula (R-PhSe)(2) (R = CH3O, CH3, H, Cl, CF3) with a thiolate nucleophile, leading to the breaking of the selenium-selenium (Se-Se) bond. This process has fundamental importance in biological environments and provides a rationale to analyze the so-called thiol modifier effect of diselenides, which may be exploited in pharmacology and toxicology. Our data suggest that withdrawing substituents favor the reaction, effectively making the reaction energy more negative, but strong electron-withdrawing groups also prompt structural modification on the starting reactant, increasing the reaction barrier. Thus, the nature (electron rich or electron poor) of the diselenides can play an essential role in the reactivity and biological activity of these molecules

Enzymatic and biochemical characterization of Bungarus sindanus snake venom acetylcholinesterase

This study analyses venom from the elapid krait snake Bungarus sindanus, which contains a high level of acetylcholinesterase (AChE) activity. The enzyme showed optimum activity at alkaline pH (8.5) and 45ºC. Krait venom AChE was inhibited by substrate. Inhibition was significantly reduced by using a high ionic strength buffer; low ionic strength buffer (10 mM PO4 pH 7.5) inhibited the enzyme by 1. 5mM AcSCh, while high ionic strength buffer (62 mM PO4 pH 7.5) inhibited it by 1 mM AcSCh. Venom acetylcholinesterase was also found to be thermally stable at 45ºC; it only lost 5% of its activity after incubation at 45ºC for 40 minutes. The Michaelis-Menten constant (Km) for acetylthiocholine iodide hydrolysis was found to be 0.068 mM. Krait venom acetylcholinesterase was also inhibited by ZnCl2, CdCl2, and HgCl2 in a concentrationdependent manner. Due to the elevated levels of AChE with high catalytic activity and because it is more stable than any other sources, Bungarus sindanus venom is highly valuable for biochemical studies of this enzyme

Antioxidant Activity and Inhibitory Effect of Some Commonly used Medicinal Plants against Lipid Per-Oxidation in Mice Brain

Background: The present study compares the protective properties of aqueous extracts of six medicinal plants, Phyllanthus emblica, Terminaliachebula (black and yellow), Terminalia arjuna, Balsamodendron Mukul and Alium sativum against lipid per-oxidation in mice brain.Methods: The antioxidant activities were analyzed by lipid per-oxidation assay, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical assay, total antioxidantactivity and metal chelation.Results: The extracts (fruits and bark) showed inhibition against thiobarbituric acid reactive species (TBARS) induced by pro-oxidant (10 µM FeSO4) in mice brain. Moreover, the free radical scavenging activities of the extracts was evaluated by the scavenging of DPPH radical (IC50, 23.23±1.2 µg/ml (Phyllanthus emblica), 20.24±0.9 µg/ml (Terminalia chebula yellow) and 17.33±1.1 µg/ml (Terminalia chebula black), 19.44±0.45 µg/ml (Terminalia arjuna), 56.59±2.1 µg/ml (Balsamodendron Mukul) and . 200 µg/ml (Alium sativum).Conclusion: The higher antioxidant and inhibitory effect of Terminalia chebula black in this study could be attributed to its significantly higherphenolic content, Fe(II) chelating ability, reducing ability and free radical scavenging activity. Therefore oxidative stress in brain could be potentiallyprevented by the intake of these plants.Key words: Antioxidant activity, Balb c mice, iron chelation, phenolics, oxidative stress, medicinal plants