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Lithium inhibits aluminum-induced apoptosis in rabbit hippocampus, by preventing cytochrome c translocation, Bcl-2 decrease, Bax elevation and caspase-3 activation.

A variety of studies on neuronal death models suggest that lithium has neuroprotective properties. In the present investigation, we have examined the effect of chronic lithium treatment on hippocampus, as monitored by changes at the subcellular level of apoptosis-regulatory proteins which have been induced by the neurotoxin, aluminum maltolate. Intracisternal administration of aluminum into rabbit brain induces cytochrome c release, decreases levels of the anti-apoptotic proteins Bcl-2 and Bcl-X(L), increases levels of the pro-apoptotic Bax, activates caspase-3, and causes DNA fragmentation as measured by the TUNEL assay. Pretreatment for 14 days with 7 mm of lithium carbonate in drinking water prevents aluminum-induced translocation of cytochrome c, and up-regulates Bcl-2 and Bcl-X(L,) down-regulates Bax, abolishes caspase-3 activity and reduces DNA damage. The regulatory effect of lithium on the apoptosis-controlling proteins occurs in both the mitochondria and endoplasmic reticulum. We propose that the neuroprotective effect of lithium involves the modulation of apoptosis-regulatory proteins present in the subcellular organelles of rabbit brain.

Administration, Oral↗

Na2Si3O7: an incommensurate structure with crenel-type modulation functions, refined from a twinned crystal.

The structure of metastable, incommensurately modulated Na(2)Si(3)O(7) has been determined from single-crystal X-ray diffraction data. In contrast to previous investigations which stated that the compound crystallizes in an orthorhombic space group, this study shows that the compound is monoclinic with a pseudo-orthorhombic cell and is affected by twinning. The structure is described in the (3 + 1)-dimensional superspace. Crenel-type modulation functions are used to account for an aperiodic sequence of right- and left-handed zweier single chains of silicate tetrahedra. The modulation mainly affects one of the two symmetrically independent tetrahedral chains, which are connected to build up [Si(3)O(7)](2-) layers. Sodium cations are coordinated by five oxygen ligands and provide linkage between adjacent tetrahedral sheets. Distortions of the silicate tetrahedra and crystal chemical relationships of the title compound to sodium and lithium di- and metasilicates are discussed in detail.

Journal Article↗

A novel 3,4-bis(sulfenyl)- or 4-selenenyl-3-sulfenylpenta-2,4-dienylation of aldehydes using 4-ethoxy-1,2-bis(sulfenyl)- or 1-Selenenyl-2-sulfenyl-buta-1,3-dienyl lithiums.

3,4-Dichalcogenopenta-2,4-dienylation of aldehydes proceeded in good to high yields using 4-ethoxy-1-(benzenesulfenyl)-2-(methanesulfenyl)- (5), 4-ethoxy-1,2-bis(benzenesulfenyl)but-1,3-diene (6), and 1-selenenyl derivatives 7 and 8. This novel four-carbon homologation could be applied to a synthesis of 3,4,7,8-tetrakis(benzenesulfenyl)-10,10-dimethylundeca-2,4,6,8-tetraenal (20).

Aldehydes↗

Ab initio studies of the decomposition of nitrosourea in the presence of cations.

Self-consistent (Hartree-Fock) calculations of the process of decomposition of protonated and lithiated syn-N-nitrosourea show that the presence of cations perturbs the electron distribution significantly. The decomposition of nitrosourea is facilitated when a proton or lithium ion is positioned at the oxygen of the nitroso group. These results may suggest clinical experimentation with nitrosoureas used in conjunction with lithium salts.

Drug Stability↗

Na(+)-induced reversal of the Ca2(+)-dependent red-shift of cytochrome a. Is there a hydronium output well in cytochrome c oxidase?

The Ca2(+)-induced red shift of the cytochrome a absorption spectrum is counteracted specifically by Na+ ions, whereas neither K+ nor Li+ do show comparable effect. At the same time Na+ does not reverse the H(+)-induced red shift of cytochrome a 2+. It is suggested that Na+ competes with Ca2+ for binding site(s) within the cytochrome oxidase output proton well communicating the heme a propionate substituent responsible for the Ca2(+)- or H(+)-induced red-shift of cytochrome a (Saari et al. 1980, J. Bioenerget. Biomembr. 12, 325-338) with the c-aqueous phase. The unusual ionic specificity of the well (Ca2+, Na+, proton) may point to H3O+ rather than H+ being the ion involved in proton conduction through the output well of cytochrome oxidase.

Animals↗

[A neurophysiological analysis of the serotoninergic effects of lithium oxybutyrate].

Single intravenous injections of lithium hydroxybutyrate (10 mg/kg) to rabbits prevented the effects of stimulation of the dorsal nucleus of the raphe on the electrogenesis of the cortex and subcortical structures. At long-term administration (7 days, 10 mg/kg daily intramuscularly) lithium hydroxybutyrate prevented the influence of stimulation on the electrogram (EG) of this structure and the motor cortex but enhanced it with respect to EG of the amygdala, hippocampus, thalamus and caudate nucleus.

Animals↗

[Effect of sodium, lithium and amiloride on the K+-dependent phosphatase activity of membrane preparations of Na,K-ATPase].

Effects of sodium, lithium and amiloride on the ATPase reaction and on its potassium-dependent step were studied using membrane preparations of Na,K-ATPase. It was established that the addition of 70 mM NaCl or LiCl to the reaction medium diminished the hydrolysis of para-nitrophenyl phosphate (pNPP) by 70 and 40%, respectively. Amiloride (0.8 mM) inhibited activities of Na,K-ATPase and pNPPase by 50 and 15%, respectively. The higher concentrations of amiloride produced a more prominent inhibition of Na,K-ATPase, but not of pNPPase. There was no correlation between the effect of amiloride on the pNPP hydrolysis and potassium concentration in the medium. There was the additivity in the inhibition of pNPPase by 0.8 mM amiloride and sodium or lithium ions up to the concentrations of ions as high as 30 mM. A conclusion is made that the inhibition of Na,K-ATPase by amiloride is mediated through the modification of the sensitivity of the enzyme to sodium.

4-Nitrophenylphosphatase↗

Acetylenic and allenic derivatives of 2-(1-methylindolyl) methylamine as selective inhibitors of the monoamine oxidases A and B.

This paper reports the synthesis of a new series of acetylenic and allenic derivatives of 2-(1-methylindolyl) methylamine as well as the preliminary results of their study as selective inhibitors of the A and B forms of the mitochondrial monoamine oxidase from bovine brain. The compounds were obtained from 2-(1-methylindole)carboxylic acid which, as its acyl halide, reacts with amines to give the respective amides. The latter compounds were reduced with lithium aluminium hydride to the respective amines (II a-c) and then N-alkylated by reaction with 2-propynyl-, 2-butynyl- or 2,3-butadienyl bromides to the corresponding amines (III a-j).

Alkenes↗

[Protective action of antioxidant preparations on the development of experimental allergic encephalomyelitis in guinea pigs].

The authors studied the action of combined tocopherol, lithium hydroxybutyrate and pyridoxal phosphate on the development of experimental allergic encephalomyelitis (EAE) in guinea-pigs. The use of the combined drug from the first days of immunization with encephalitis-inducing material prevented the development of EAE, activation of lipid peroxidation (LPO), and the appearance of the blood serum neurotropic activity. Administration of the combined drug starting from the 7th day after immunization appeared ineffective as was the administration of each drug alone, starting from the first days of immunization. The data obtained support an important role of LPO activation for the pathogenesis of the neuroallergic process.

Animals↗