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Local anesthetics induce human renal cell apoptosis
H Thomas Lee1, Hua Xu, Cory D Siegel
1Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, NY 10032-3784, USA. tl128@columbia.edu
American Journal of Nephrology
|February 15, 2003
Summary
Local anesthetics like lidocaine induce programmed cell death (apoptosis) in human kidney cells. This occurs through caspase activation and inhibition of survival pathways, independent of sodium channel effects.
Area of Science:
- Nephrology
- Pharmacology
- Cell Biology
Background:
- Renal cell apoptosis is a key factor in acute kidney injury.
- Local anesthetics are known to induce apoptosis in various cell types.
Purpose of the Study:
- To investigate the effects of chronic local anesthetic exposure on human kidney proximal tubular cells (HK-2).
- To elucidate the mechanisms by which local anesthetics induce apoptosis in renal cells.
Main Methods:
- HK-2 cells were treated with lidocaine, bupivacaine, and tetracaine for 48 hours.
- Apoptosis was assessed using poly(ADP)-ribose polymerase fragmentation, caspase activation assays, TUNEL staining, DNA laddering, and morphological analysis.
- Cell death was quantified via neutral red dye uptake and lactate dehydrogenase release.
Main Results:
- All tested local anesthetics induced concentration-dependent cell death and apoptosis in HK-2 cells.
- Local anesthetics activated caspases 3, 6, 7, 8, and 9, which was blocked by a pan-caspase inhibitor.
- These agents inhibited pro-survival kinases Akt and ERK, and their pro-apoptotic effects were independent of sodium channel blockade.
Conclusions:
- Local anesthetics induce apoptosis in human renal cells through caspase activation.
- Local anesthetics inhibit pro-survival signaling pathways, contributing to renal cell apoptosis.
- The pro-apoptotic effects are not mediated by sodium channel inhibition.