Effect of N-acetylcysteine route of administration on chemoprotection against cisplatin-induced toxicity in rat models

D. Thomas Dickey, Leslie L. Muldoon, Nancy D. Doolittle, Darryl R. Peterson, D. Kraemer, Edward A. Neuwelt

Research output: Contribution to journalArticle

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Abstract

Dosing and route of administration of N-acetylcysteine (NAC) for protection against cisplatin (CDDP) nephrotoxicity was investigated in rats. Two models of toxicity were tested: a single high dose of CDDP (10 mg/kg intraperitoneally (IP)), and multiple low dose treatments (1 mg/kg IP twice a day for 4 days, 10 days rest, then repeated). NAC (50-1,200 mg/kg) was given to the rats by IP, oral (PO), intravenous (IV) and intra-arterial (IA) routes. Renal toxicity was determined by blood urea nitrogen (BUN) and creatinine (CR) levels 3 days after treatment. Blood collected 15 min after NAC was analyzed for total NAC. Both models of CDDP administration produced renal toxicity. In the single dose CDDP model, NAC 400 mg/kg given IP and PO produced no renal protection as measured by BUN (131.8 ± 8.2 and 123.3 ± 8.2, respectively) or CR (2.3 ± 0.38 and 1.77 ± 0.21, respectively). IV NAC reduced nephrotoxicity, (BUN 26.3 ± 6.8, CR 0.47 ± 0.15). NAC 50 mg/kg IA gave better protection than IV. In the repeated-dose CDDP model, nephrotoxicity was blocked by 800 mg/kg NAC given IV but not IP. Blood concentrations of total NAC showed a dose response after IV NAC, but high dose NAC (1,200 mg/kg) by the PO route gave very low levels of NAC. Thus the protective properties of NAC are affected by the dose and route of administration.

Original languageEnglish
Pages (from-to)235-241
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Volume62
Issue number2
DOIs
Publication statusPublished - Jul 2008

Fingerprint

Acetylcysteine
Cisplatin
Toxicity
Rats
Blood
Blood Urea Nitrogen
Urea
Creatinine
Nitrogen
Kidney

Keywords

  • Chemoprotection
  • Cisplatin
  • N-acetylcysteine
  • Rats
  • Route

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

Effect of N-acetylcysteine route of administration on chemoprotection against cisplatin-induced toxicity in rat models. / Dickey, D. Thomas; Muldoon, Leslie L.; Doolittle, Nancy D.; Peterson, Darryl R.; Kraemer, D.; Neuwelt, Edward A.

In: Cancer Chemotherapy and Pharmacology, Vol. 62, No. 2, 07.2008, p. 235-241.

Research output: Contribution to journalArticle

Dickey, D. Thomas ; Muldoon, Leslie L. ; Doolittle, Nancy D. ; Peterson, Darryl R. ; Kraemer, D. ; Neuwelt, Edward A. / Effect of N-acetylcysteine route of administration on chemoprotection against cisplatin-induced toxicity in rat models. In: Cancer Chemotherapy and Pharmacology. 2008 ; Vol. 62, No. 2. pp. 235-241.
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