In Vitro Metabolomic Approach to Hippocampal Neurodegeneration Induced by Trimethyltin.

Search for indicators of neurodegenerative disorders is a hot topic where much research remains to be done. Our aim was to determine proton nuclear magnetic resonance ((1)H-NMR) spectra of brain metabolites in the trimethyltin (TMT) model of neurodegeneration. Male Wistar rats were subjected to TMT or saline and were sacrificed on day 3 or 24 after administration. (1)H-NMR spectrum was measured on the 600 MHz Varian VNMRS spectrometer in nano-probe in the volume of 40 µl of hippocampal extracts. TMT administration resulted in reduction of the hippocampal weight on day 24. Of the sixteen identified metabolite spectra, decreased aspartate and increased glutamine contents were observed in the initial asymptomatic stage of neurodegeneration on day 3 in hippocampal extracts of TMT exposed rats compared to sham animals. Increased myo-inositol content was observed on day 24. The presented data provide further knowledge about this experimental model and putative indicators of neuronal damage.

Mechanism of anti-inflammatory action of liquorice extract and glycyrrhizin.

The antiradical activity, protective effect against lipid peroxidation of liposomal membrane, and inhibitory effect on whole blood reactive oxygen species (ROS) liberation of Glycyrrhiza glabra crude extract and glycyrrhizin, its major compound, were assessed. The liquorice extract showed significant activity in all the three assay systems used in a dose dependent manner. It displayed remarkable reactivity with free stable 1,1'-diphenyl-2-picrylhydrazyl (DPPH) radical, inhibitory efficacy in peroxidatively damaged unilamellar dioleoyl phosphatidylcholine (DOPC) liposomes, and inhibition of ROS chemiluminescence, generated by whole blood, induced by both receptor-bypassing stimuli (PMA) and receptor operating stimuli (Opz) in the ranking order of stimuli PMA> Opz. These activities may be attributed to phenolic antioxidants involving isoflavan derivatives, coumarins and chalcones. Nonetheless, triterpene saponin glycyrrhizin exhibited no efficacy in the system of DPPH reaction and peroxidation of liposomal membrane, and negligible inhibition of chemiluminescence generated by inflammatory cells. These results indicate that the mechanism of anti-inflammatory effect of glycyrrhizin most probably does not involve ROS and this major constituent is not responsible for the inhibition effects of liquorice extract on neutrophil functions.

Study of Trichoderma viride metabolism under conditions of the restriction of oxidative processes.

Trichoderma viride was capable of growth and conidiation in the presence of high concentrations of the uncoupler 3,3',4',5-tetrachlorosalicylanilide (up to 100 micromol x L(-1) and of the respiration inhibitor mucidin (up to 100 micromol x L(-1) ) in both submerged and surface cultivation. When vegetative mycelia were cultivated on the solid Czapek-Dox medium with yeast autolysate under an anaerobic and CO2-containing atmosphere, the growth was observed only rarely but the microorganism survived as long as 3 months under these conditions. Major products of metabolism of both aerobic and anaerobic submerged mycelia were identified by means of 1H-NMR measurements. Major products excreted to the medium under aerobic conditions were succinic and citric acids. Major metabolites present in the submerged mycelia were gamma-aminobutyric (and glutamic) acid and alanine. Under anaerobic conditions, citric acid was not excreted into the medium but ethanol appeared. Its production could not be increased upon increasing the sugar concentration. The appearance of secondary metabolites was found to be modified by oxygen availability during the mycelial growth. Results suggest that the vegetative form of T. viride is capable of fermentative metabolism characterized by the production of ethanol and succinate and that the excretion of carboxylic acids is developmentally regulated and modified by oxygen availability.