Diclofenac induced in vivo nephrotoxicity may involve oxidative stress-mediated massive genomic DNA fragmentation and apoptotic cell death

Diclofenac is a nonsteroidal anti-inflammatory drug that is widely used for the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and acute muscle pain conditions

E.J Hickey; R.R Raje; V.E Reid; S.M Gross; S.D Ray

2002

Scholarcy highlights

  • Diclofenac is a nonsteroidal anti-inflammatory drug that is widely used for the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and acute muscle pain conditions
  • Toxic doses of DCLF can cause nephrotoxicity in humans and experimental animals. Whether this DCLF-induced nephrotoxicity involves apoptotic cell death in addition to necrosis is unknown. The goals of this investigation were to determine whether DCLF-induced nephrotoxicity involves oxidative stress and apoptotic type genomic DNA fragmentation, and if so, whether DCLF-induced oxidative stress and DNA fragmentation cause apoptotic cell death in mouse kidneys
  • Results show that diclofenac is a powerful nephrotoxicant and a strong inducer of oxidative stress
  • A dose-dependent increase in MDA levels and superoxide dismutase activity was observed, which indicated a link between oxidative stress and nephrotoxicity
  • Histopathological examination of kidney sections revealed numerous apoptotic nuclei across proximal and distal tubular cell linings. These data for the first time suggest that DCLF-induced nephrotoxicity may involve production of reactive oxygen species leading to oxidative stress and massive genomic DNA fragmentation, and these two free radical mediated events may translate into apoptotic cell death of kidney cells in vivo, and reveal a DNA-active role for DCLF

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