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Nephrotoxic cell death by diclofenac and meloxicam
Lin Eng Ng1, Barry Halliwell, Kim Ping Wong
1Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore.
Biochemical and Biophysical Research Communications
|March 8, 2008
Summary
Diclofenac is more toxic to kidney cells than meloxicam, inducing necrosis. Meloxicam triggers apoptosis in kidney cells, indicating different toxicity mechanisms for these non-steroidal anti-inflammatory drugs.
Area of Science:
- Nephrology
- Toxicology
- Cell Biology
Background:
- Non-steroidal anti-inflammatory drugs (NSAIDs) like diclofenac and meloxicam are widely used.
- Diclofenac, a dual cyclooxygenase (COX) inhibitor, has shown fatal nephrotoxicity in vultures.
- Meloxicam, a COX-2 selective NSAID, exhibits a different toxicity profile.
Purpose of the Study:
- To compare the nephrotoxicity of diclofenac and meloxicam in vitro.
- To elucidate the mechanisms of cell death induced by these NSAIDs in different kidney cell lines.
Main Methods:
- Utilized LLC-PK1 (proximal tubular) and Madin-Darby canine kidney type II (MDCKII) (distal tubular) cell lines.
- Assessed cell viability and death pathways, including apoptosis and necrosis.
- Measured caspase activation, cytochrome c release, and annexin V-FITC/propidium iodide staining.
Main Results:
- Diclofenac demonstrated higher toxicity than meloxicam in both cell lines.
- LLC-PK1 cells were more susceptible to NSAID toxicity than MDCKII cells.
- Meloxicam induced apoptosis in MDCKII cells via the intrinsic mitochondrial pathway.
- Diclofenac induced necrosis in MDCKII cells.
- LLC-PK1 cells exhibited a less defined cell death pathway, potentially caspase-independent.
Conclusions:
- Diclofenac and meloxicam exhibit differential nephrotoxicity and induce distinct cell death pathways.
- The COX selectivity of NSAIDs influences their kidney toxicity mechanisms.
- Understanding these mechanisms is crucial for assessing the safety of NSAIDs in clinical and veterinary settings.
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