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Published on: January 15, 2011
Effects of idebenone on mitogen-induced proliferation of human lymphocytes
1Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
Insights
Idebenone did not affect human lymphocyte function at low doses. Higher concentrations suppressed proliferation and protein synthesis, but therapeutic doses are unlikely to cause immunologic suppression in vivo.
Area of Science:
- Immunology
- Pharmacology
Background:
- Idebenone is a synthetic compound with antioxidant properties.
- Its effects on immune cells, particularly human lymphocytes, require detailed investigation.
Purpose of the Study:
- To investigate the in vitro effects of idebenone on human lymphocytes from both young and old donors.
- To determine the dose-dependent impact of idebenone on lymphocyte proliferation, protein synthesis, and viability.
Main Methods:
- Human lymphocytes from young and old donors were isolated.
- Cells were treated with varying concentrations of idebenone.
- Phytohemagglutinin (PHA)-induced proliferation, protein synthesis (using radiolabeled amino acids), and cell viability (Trypan Blue exclusion) were assessed.
- Expression of stress proteins HSP70 and HSP90 was analyzed.
Main Results:
- Idebenone showed no significant effect on lymphocyte viability, proliferation, or protein synthesis at concentrations up to 2 microg/ml.
- Dose-dependent suppression of proliferation and protein synthesis, along with cytotoxicity, was observed at 25 and 50 microg/ml.
- Slight enhancement of intracellular stress proteins HSP70 and HSP90 was noted at higher idebenone concentrations.
- Effects were consistent across lymphocytes from both young and old donors.
Conclusions:
- In vitro studies suggest idebenone has minimal impact on lymphocyte function at concentrations likely achievable in vivo.
- Higher idebenone concentrations exhibit dose-dependent immunosuppressive and cytotoxic effects.
- Therapeutic doses of idebenone are unlikely to cause significant lymphopenia or immunologic suppression.
Abstract:
In vitro effect of idebenone on human lymphocytes isolated from old and young donors was determined. The effects of drug were the same with the old and young donors cells. At concentrations of 2 microg/ml (6 microM) or less in the culture medium, idebenone showed no effect on phytohemagglutinin (PHA)-induced proliferation and protein synthesis, or on cell viability measured by Trypan Blue exclusion. Concentrations of 25 and 50 microg/ml showed dose-dependent suppression of the proliferation and protein synthesis which was associated with significant cytotoxicity. At concentrations of 8-10 microg/ml the compound appears to have just detectable effect on lymphocyte viability or ability to respond to PHA stimulation. It seems clear that such in vivo concentrations which would be associated with lymphopenia and immunologic suppression are not achieved with therapeutic doses of idebenone. The pattern of protein bands observed on fluorograms of sodium dodecyl sulfate-polyacrylamide gels of cells incubated with [(3)H]leucine and [(35)S]methionine was similar in control and idebenone-treated samples, consistent with a slight, nonspecific inhibitory effect on protein synthesis in cultures with higher doses of the compound. At these concentrations, idebenone induced a slight, but detectable, enhancement of the intracellular stress proteins, HSP70 and HSP90.
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