Levels and sub-cellular distribution of physiologically important metal ions in neuronal cells cultured from chick embryo cerebral cortex.

Mg2+, Ca2+, Mn2+, Zn2+, and Cu content of neurons from chick embryo cortex cultivated in chemically defined serum free growth medium was determined by energy dispersive X-ray fluorescence and atomic absorption spectroscopy. The intracellular volume of cultured neurons was determined to be 2.73 microliters/mg.

Acute toxicity of helenalin in BDF1 mice.

The acute toxicity of helenalin, a sesquiterpene lactone isolated from Helenium microcephalum, was examined in male BDF1 mice. The 14-day LD50 for a single ip dose of helenalin in male mice was 43 mg/kg. A single ip injection of 25 mg helenalin/kg increased serum alanine aminotransferase (ALT), lactate dehydrogenase (LDH), urea nitrogen (BUN), and sorbitol dehydrogenase within 6 hr of treatment.

Inhibition of nucleic acid synthesis in P-388 lymphocytic leukemia tumor cells by helenalin and bis(helenalinyl)malonate in vivo.

Although the parent sesquiterpene lactone, helenalin, and its derivative, bis(helenalinyl)malonate, are structurally related chemically, they demonstrate differences in their antineoplastic activity, with bis(helenalinyl)malonate being much more active against P-388 lymphocytic leukemia cell growth (T/C% = 261) compared with helenalin (T/C% = 162). Previous studies have shown that both agents strongly inhibit protein synthesis in vivo by greater than 70% after 3 d of administration and in vitro by 50% at a 100 microM concentration of drug. This inhibition of protein synthesis of P-388 cells may be partially responsible for the cytotoxicity of the drug.

Concentrations of physiologically important metal ions in glial cells cultured from chick cerebral cortex.

Energy dispersive x-ray fluorescence and atomic absorption spectroscopy were used to determine the concentrations of Mg, Ca, Mn, Fe, Zn, and Cu in primary cultures of astroglial cells from chick embryo cortex in chemically defined serum-free growth medium. The intracellular volume of cultured glia was determined to be 8.34 microliter/mg protein.

Inhibition of nucleic acid synthesis in P-388 lymphocytic leukemia cells in culture by sesquiterpene lactones.

Helenalin and bis (helenalinyl) malonate, sesquiterpene lactones, were shown to be cytotoxic against the growth of P-388 lymphocytic leukemia cells in culture. DNA and protein synthesis were reduced by these agents preferentially, with RNA synthesis being affected only marginally. This study focused on the identification of the enzyme target(s) responsible for the inhibition of DNA synthesis by the sesquiterpene lactones.

Effect of helenalin and bis(helenalinyl)malonate on nucleic acid and protein synthesis in human KB carcinoma cells.

Helenalin and bis(helenalinyl)malonate were shown to be cytotoxic against the growth of human KB carcinoma cells. DNA synthesis was inhibited significantly. This inhibition was afforded because of the drugs' effects on a number of enzyme activities.

Effects of [(N-alkyl-1,3-dioxo-1H,3H-isoindolin-5-yl)oxy]alkanoic acids, [(N-alkyl-1-oxo-1H,3H-isoindolin-5-yl)oxy]butanoic acids, and related derivatives on chloride influx in primary astroglial cultures.

It has been shown that agents that inhibit chloride influx and therefore lower intracellular chloride levels in a major cell type in cerebral gray matter, the astrocyte, inhibit astrocytic swelling in vitro and in vivo. In our laboratories, 4-[(N-alkyl-1,3-dioxo-1H,3H-isoindolin-5-yl)oxy]alkanoic acids and related derivatives have been synthesized and tested for ability to lower intracellular astrocytic chloride levels in an established in vitro cultured rat astrocyte model. In general, derivatives with nitrogen substituents such as relatively small alkyl groups are active at 0.