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Nephrotoxic cell death by diclofenac and meloxicam.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2008 May 09; Vol. 369 (3), pp. 873-7. Date of Electronic Publication: 2008 Mar 04. - Publication Year :
- 2008
-
Abstract
- The nephrotoxicity of diclofenac, a non-steroidal anti-inflammatory drug that inhibits both isoforms of cyclooxygenase (COX) has been reported to be fatal to vultures but this was not so with meloxicam which is COX-2 selective. Our study showed that diclofenac was more toxic than meloxicam to both the proximal tubular LLC-PK1 cells and the distal tubular Madin-Darby canine kidney type II (MDCKII) cells, and that LLC-PK1 cells were more susceptible. Exposure of MDCKII cells to meloxicam caused activation of caspase-9/-3 and release of cytochrome c. These observations together with a positive annexin V-FITC staining implicate an intrinsic mitochondrial cell death pathway by apoptosis. Diclofenac-treated MDCKII cells on the other hand showed extensive propidium iodide staining, suggestive of cell death by necrosis. The mode of cell death in LLC-PK1 cells was however less well-defined with positive annexin V-FITC staining but minimal increase in caspase-3 activity alluding to a caspase-independent pathway.
- Subjects :
- Animals
Annexin A5 chemistry
Caspase 3 metabolism
Caspase 8 metabolism
Caspase 9 metabolism
Cell Survival drug effects
Coloring Agents chemistry
Cytochromes c metabolism
Dogs
Fluorescein-5-isothiocyanate analogs & derivatives
Fluorescein-5-isothiocyanate chemistry
Humans
Kidney Tubules cytology
Kidney Tubules enzymology
Meloxicam
Propidium chemistry
Staining and Labeling
Anti-Inflammatory Agents, Non-Steroidal toxicity
Apoptosis
Cyclooxygenase Inhibitors toxicity
Diclofenac toxicity
Kidney Tubules drug effects
Thiazines toxicity
Thiazoles toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 369
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 18325323
- Full Text :
- https://doi.org/10.1016/j.bbrc.2008.02.116