Possible involvement of oxidative stress in cisplatin-induced apoptosis in LLC-PK1 cells

T. Xiao, S. Choudhary, W. Zhang, Naseem Ansari, A. Salahudeen

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Use of cisplatin, a chemotherapeutic agent, is associated with toxicity as a significant number of patients develop a decline in renal function. The mechanisms by which cisplatin produces renal injury are not well understood. It has been suggested that free radical-catalyzed lipid peroxidation can induce apoptosis or necrosis leading to renal injury. This study examined whether low concentrations of cisplatin induce apoptosis in LLC-PK1 cells and whether caspases 1, 2, 3, 8, and 9 are activated during this event. Our results show a dose- and time-dependent induction of apoptosis by micromolar concentrations of cisplatin. Expression of oncogenes c-myc and p53 was induced, and except for caspase 1, all the other caspases tested were activated. Z-VAD, the broad-spectrum inhibitor of caspases, prevented caspase activation and apoptosis, but not c-myc and p53 induction. On the other hand, N-acetylcysteine prevented cisplatin-induced apoptosis as well as c-myc induction but not p53 induction. The antioxidant trolox also prevented cisplatin-induced apoptosis. The results suggest that antioxidants and caspase inhibitors may alleviate cisplatin-associated nephrotoxicity.

Original languageEnglish (US)
Pages (from-to)469-479
Number of pages11
JournalJournal of Toxicology and Environmental Health - Part A
Volume66
Issue number5
DOIs
StatePublished - Mar 14 2003

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LLC-PK1 Cells
Oxidative stress
apoptosis
Cell death
Cisplatin
Oxidative Stress
Apoptosis
Caspase 1
Caspase Inhibitors
Antioxidants
antioxidant
Caspases
inhibitor
Kidney
Acetylcysteine
Caspase 2
free radical
myc Genes
Free radicals
Wounds and Injuries

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Public Health, Environmental and Occupational Health
  • Pollution
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Possible involvement of oxidative stress in cisplatin-induced apoptosis in LLC-PK1 cells. / Xiao, T.; Choudhary, S.; Zhang, W.; Ansari, Naseem; Salahudeen, A.

In: Journal of Toxicology and Environmental Health - Part A, Vol. 66, No. 5, 14.03.2003, p. 469-479.

Research output: Contribution to journalArticle

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AU - Salahudeen, A.

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