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ARMIN WOLF ANAL REAL ACAD. FARM.

Lo Russo et al. 1996) Reactive oxygen species (ROS) are also supposed
to be inducers of apoptosis in various in vitro cellular systems (Jabs
1999), and in agreement with this, inhibition of apoptotic cell death has
been observed with antioxidants (Jabs 1999). Under certain
circumstances, ROS might serve to trigger the increase in intracellular
Ca2+ concentrations, and, by this process, leading to the induction of
apoptosis (Orrenius 1993); a mechanism different from that with
caspases. We have also recently found that CsA induced the formation of
ROS, which makes the assumption of such a mechanism very likely
(Wolf et al. 1997).

In summary, the present results showed that, in rat hepatocyte
primary cultures, CsA specifically induced apoptosis after short-term
incubation; this overlapped with necrosis after longer-term incubation. It
is likely that the necrosis which occurrs after 20 hours is, partially, a
secondary result of apoptosis.

ACKNOWLEDGEMENTS

We would like to thank B. Greiner and M. Gianella for their
excellent technical assistance, and Dr. W. Seewald from Aicos, Basel,
Switzerland, for performing the various statistical analyses.

REFERENCES

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SIKIC B. I., GREEBERG P. L. (1999). Treatment of refractory and relapsed
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(2) BOELSTERLI U. A., WOLF A., GÖLDLIN C. (1993). Oxygen free radical
production mediated by cocaine and its ethanol-derived metabolite,
cocaethylene, in rat hepatocytes. Hepatology 18, 1154-61.

(3) BRADFORD M. A. (1976). Rapid and sensitive method for the quantification
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