Search NEL Online

Journal Article 2013; 34(7): 648-654 PubMed PMID: 24464007 Citation  Keywords:  Animals, Antimanic Agents:pharmacology, Cell Death:drug effects, Cell Line, Tumor, Drug Interactions, Hydrogen Peroxide:pharmacology, Inhibitory Concentration 50, Lithium Compounds:pharmacology, Motor Neurons:cytology, NF-E2-Related Factor 2:metabolism, N.   

OBJECTIVE: Lithium and valproic acid (VPA) have been reported to produce antioxidant effects by increasing the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expression, which may contribute to their neuroprotective properties. As a coactivator for many transcriptional factors including PGC-1α, coactivator-associated arginine methyltransferase1(CARM1) regulates oxidative metabolism and mitochondrial biogenesis. Besides, Sirtuin3 (SIRT3), a new target of PGC-1α, plays an important role in preserving mitochondrial function.

RESULTS: Here we found that protein levels of SIRT3 and CARM1 were decreased during oxidative stress in motor neuronal cells (NSC34). Pretreatment of NSC34 cells with lithium (5 mmol/L), VPA (1 mmol/L), or lithium plus VPA for 24 hours, significantly reduced hydrogen peroxide (H2O2)-induced cytotoxicity, and increased SIRT3 and CARM1 levels.

CONCLUSION: Our results suggest that lithium and VPA may decrease vulnerability of motor neuronal cells to cellular injury evoked by oxidative stress, which possibly arising from putative mitochondrial disturbances. And further study of the molecular mechanisms of SIRT3 and CARM1 regulation may provide a novel target for treating motor neuron disease....

Read abstract  Full text PDF

Journal Article 2010; 31(3): 343-347 PubMed PMID: 20588245 Citation  Keywords:  Alkenes:metabolism, Animals, Dose-Response Relationship, Drug, Female, Ferrous Compounds:pharmacology, Hydrogen Peroxide:pharmacology, In Vitro Techniques, Lipid Peroxidation:drug effects, Malondialdehyde:metabolism, Ovary:drug effects, Swine,.   

OBJECTIVE: Substrates of Fenton reaction (Fe(2+)+H(2)O(2)-->Fe(3+)+*OH+OH-) may be used to experimentally induce oxidative damage to macromolecules. The study aimed at evaluating effects of Fe(2+) and/or H(2)O(2) on lipid peroxidation in porcine ovary homogenates.

MATERIALS AND METHODS: Ovary homogenates were incubated in the presence of either H2O2 (100, 50, 25, 10, 5.0, 2.5, 1.0, 0.5, 0.25, 0.01, 0.001 mM) or FeSO(4) (Fe2+) (300, 150, 75, 30, 15, 7.5, 3.0, 1.5, 0.75 microM), or of those two factors used together: Fe(2+) (30 microM) plus H(2)O(2) (concentrations as above), or H(2)O(2) (0.5 mM) plus Fe(2+) (concentrations as above). The concentration of malondialdehyde+4-hydroxyalkenals constituted the lipid peroxidation index.

RESULTS: H(2)O(2) alone did not affect lipid peroxidation in porcine ovary homogenates at all, whereas Fe(2+) (300, 150, 75, 30, and 15 microM) alone increased lipid peroxidation in a concentration dependent manner. When Fe(2+) and H(2)O(2) were applied together, lipid peroxidation increased significantly without any concentration related effect of H(2)O(2), but with a clear concentration dependent effect of Fe(2+); the damaging effect of Fe(2+), used together with H(2)O(2), was the same as the one, obtained after Fe(2+) was applied alone.

CONCLUSIONS: In conclusion, external H(2)O(2) is not indispensable for experimental induction of lipid peroxidation by Fenton reaction in porcine ovary homogenates....

Read abstract  Full text PDF

Comparative Study 2006; 27(Suppl 2): 31-34 PubMed PMID: 17159774 Citation  Keywords:  Hyaluronic Acid:chemistry, Hydrogen Peroxide:pharmacology, Manganese Compounds:pharmacology, Models, Biological, Molecular Weight, Oxides:pharmacology, Peroxynitrous Acid:chemical synthesis, Viscosity,.   

OBJECTIVES: This contribution presents the results of the kinetics of HA degradation by peroxynitrite, which represents one of the main reactive oxygen species degrading various biomacromolecules under inflammatory conditions.

METHODS: Two simple procedures have been adapted to prepare sodium peroxynitrite: the first containing an excess of H(2)O(2), and the second in which the H(2)O(2) excess had been decomposed by MnO(2) treatment. The kinetics of hyaluronan degradation by action of peroxynitrite was monitored by rotational viscometry.

RESULTS: High-molecular-weight hyaluronan was degraded by peroxynitrite. The degradation was increased in the presence of ONOO(-) previously treated by MnO(2) in order to remove residual hydrogen peroxide. One of the reasons of this finding could be that by the action of the residual metal the pathway of ONOO(-) decomposition starts to be manifested immediately on mixing traces of metals originally present in the HA sample with the ions of manganese.

CONCLUSIONS: Trace amounts of transition metal(s) should be taken into consideration on evaluating the experimental results. Purchase of the marketed peroxynitrite product appears to be the appropriate approach to simplify and standardize the quality of ONOONa....

Read abstract