Inhibition of amine oxidases by the histamine-1 receptor antagonist hydroxyzine.

The effects of the drug hydroxyzine on the activities of the rat liver monoamine oxidases (EC 1.4.3.6; MAO) and the membrane-bound and soluble forms of bovine semicarbazide-sensitive amine oxidase (EC 1.4.3.6; SSAO) were studied. Hydroxyzine was found to be a competitive inhibitor of MAO-B (Ki - 38 microM), whereas it had a low potency towards MAO-A (IC50 > 630 microM). Although it was a relatively potent competitive inhibitor of bovine plasma SSAO (Ki approximately 1.5 microM), it was a weak inhibitor of the membrane-bound form of the enzyme from bovine lung (IC50 approximately 1 mM). These findings extend our knowledge of the drug binding capabilities of the amine oxidases and suggest that these interactions may contribute to the complex actions of this drug.

It can be a complicated life being an enzyme.

It is becoming increasingly apparent that many well-known enzymes have alternative non-enzymic functions. Similarly, several proteins that were identified as having non-catalytic functions were subsequently found to have enzyme activities. Some examples are considered to illustrate the diversity of alternative functions. The semicarbazide-sensitive amine oxidase (EC 1.4.3.6) is considered in more depth as an example. It was originally believed to be a detoxifying enzyme, but the reaction products may have important signalling functions. Furthermore, this enzyme, from some sources, also behaves as a vascular-adhesion protein. Finally, the challenges posed by such multiplicity of functions for the interpretation of genetic deletion, in vivo inhibition and the development of functional protein databases are briefly considered.

In vitro cytotoxicity of a composite resin and compomer.

AIM: This work was designed to investigate the potential cytotoxicity of two of the newer dental restorative materials. Spectrum composite resin and Dyract AP compomer. METHODOLOGY: Cultured human endothelial cells (ECV-304) were exposed to each of the restorative materials through a 70-microm dentine barrier to simulate the in vivo clinical situation. Cell viability was measured by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide) assay and lactate dehydrogenase release assay. The effects of different extents of light-curing were also examined by microscopic examination of stained human promyelocytic leukemia cells (HL-60). Caspase-3 activation was determined as a measure of apoptotic cell death. RESULTS: Assessment of cellular viability indicated that both materials cause cell death, with Spectrum being the more toxic. The cytotoxicity was considerably increased in the absence of the dentine barrier. Direct exposure to Spectrum for 12 h resulted in the death of 69% of the cells after full light-curing (78% of total death was by apoptosis) and 96% after partial light-curing (73% of total death was by necrosis). Assessment of caspase activation, in the absence of the dentine barrier, showed that longer curing-times resulted in an increase in the proportion of the cells dying through apoptosis, rather than necrosis, for both materials tested. CONCLUSIONS: These results indicate the restorative materials to be potentially toxic, particularly if the degree of light-cure is inadequate.