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E Aeberhard

Publications and source records attributed to E Aeberhard.

8 recordsLinked to original sources
PubMed1996

The chemistry and tumoricidal activity of nitric oxide/hydrogen peroxide and the implications to cell resistance/susceptibility.

The mechanism of cytotoxicity of the NO donor 3-morpholino-sydnonimine toward a human ovarian cancer cell line (OVCAR) was examined. It was found that the NO-mediated loss of cell viability was dependent on both NO and hydrogen peroxide (H2O2). Somewhat surprisingly, superoxide (O2) and its reaction product with NO, peroxynitrite (-OONO), did not appear to be di- rectly involved in the observed NO-mediated cytotoxicity against this cancer cell line. The toxicity of NO/H2O2 may be due to the production of a potent oxidant formed via a trace metal-, H202-, and NO-dependent process. Because the combination of NO and H2O2 was found to be particularly cytotoxic, the effect of NO on cellular defense mechanisms involving H2O2 degradation was investigated. It was found that NO was able to inhibit catalase activity but had no effect on the activity of the glutathione peroxidase (GSHPx)-glutathione reductase system. It might therefore be expected that cells that utilize primarily the GSHPx-glutathione reductase system for degrading H2O2 would be somewhat resistant to the cytotoxic effects of NO. Consistent with this idea, it was found that ebselen, a compound with GSHPx-like activity, was able to protect cells against NO toxicity. Also, lowering endogenous GSHPx activity via selenium depletion resulted in an increased susceptibility of the target cells to NO-mediated toxicity. Thus, a possible NO/H2O2/metal-mediated mechanism for cellular toxicity is presented as well as a possible explanation for cell resistance/susceptibility to this NO-initiated process.

Antineoplastic Agents↗
PubMed1994

Nitric oxide is an important mediator for tumoricidal activity in vivo.

When cultured in vitro, peritoneal macrophages, obtained from mice previously inoculated with bacillus Calmette-Guérin, release nitric oxide, which is cytostatic and/or cytolytic for tumor cells. However, it is not known whether nitric oxide has antitumor effects in vivo. Here we demonstrate that nitric oxide is an important mediator of host resistance to syngeneic and xenogeneic ovarian tumor grafts in C3HeB/FeJ mice. A murine ovarian teratocarcinoma cell line, utilized to study the mechanism of bacillus Calmette-Guérin-induced host resistance to a syngeneic ovarian tumor, proliferated when transplanted intraperitoneally. Marked tumoricidal activity was observed, however, when these murine ovarian teratocarcinoma cells were transplanted 8 days after intraperitoneal bacillus Calmette-Guérin inoculation. In studies related to xenogeneic ovarian tumor grafts, tumoricidal activity was observed after intraperitoneal transplantation of a human epithelial ovarian cancer cell line, NIH:OVCAR-3. This cell line proliferates only in athymic nude (immunologically incompetent) mice. In both sets of experiments, tumoricidal activity was reduced by inhibition of nitric oxide synthesis. These results demonstrate the tumoricidal action of nitric oxide in vivo.

Animals↗
PubMed1981

On the mechanisms of fatty acid transformations in membranes.

Concentrations of albumin in excess of 1% in the incubation mixture inhibited the elongation of added fatty acids and their incorporation into microsomal lipids whereas these reactions were not inhibited with endogenous microsomal membrane fatty acids. The results of these and other studies support the idea that such reactions of membrane lipid fatty acids with membrane-bound enzymes normally occur entirely within the membrane without release of free fatty acids to equilibrate with the fatty acid pool during the process.

Albumins↗