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Spin trap protection from tumor necrosis factor cytotoxicity
H Pogrebniak1, W Matthews, J Mitchell
1Thoracic Oncology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
The Journal of Surgical Research
|May 1, 1991
Summary
The spin trap TEMPOL protects cells from tumor necrosis factor (TNF) by mimicking superoxide dismutase. This protection is effective even when TEMPOL is added hours after TNF exposure, suggesting therapeutic potential.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Tumor necrosis factor (TNF) induces superoxide production.
- Spin traps may act as superoxide dismutase mimics to detoxify superoxide.
- Understanding free radical-lymphokine interactions is crucial for various medical conditions.
Purpose of the Study:
- To investigate the protective effect of the spin trap TEMPOL against TNF-induced cell death.
- To determine if TEMPOL can detoxify superoxide generated by TNF.
- To explore the potential therapeutic applications of TEMPOL in free radical-related conditions.
Main Methods:
- WEHI or L929 cells were exposed to TNF (500 units/ml) for 18 hours.
- TEMPOL (0-8 mM) was added simultaneously or at delayed intervals after TNF exposure.
- Cell survival was assessed, and Northern blot analysis was performed to examine SOD gene expression.
Main Results:
- TEMPOL demonstrated a dose-dependent increase in cell survival.
- 92% of WEHI cells survived with 4 mM TEMPOL, compared to 26% without TEMPOL (P<0.01).
- Protection was observed even with TEMPOL addition as late as 15 hours after TNF exposure.
Conclusions:
- TEMPOL effectively protects TNF-sensitive cells from TNF-induced injury.
- The protective mechanism does not appear to involve newly synthesized proteins or induction of MnSOD or Cu-ZnSOD genes.
- TEMPOL's ability to protect against delayed TNF exposure suggests potential utility in ischemia-reperfusion, oxygen toxicity, and sepsis.