Protection against Cisplatin-Induced Toxicities by N-Acetylcysteine and Sodium Thiosulfate as Assessed at the Molecular, Cellular, and in Vivo Levels

  title={Protection against Cisplatin-Induced Toxicities by N-Acetylcysteine and Sodium Thiosulfate as Assessed at the Molecular, Cellular, and in Vivo Levels},
  author={D. Thomas Dickey and Y J Wu and Leslie L. Muldoon and Edward A. Neuwelt},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  pages={1052 - 1058}
  • D. Dickey, Y. J. Wu, E. Neuwelt
  • Published 1 September 2005
  • Biology, Medicine
  • Journal of Pharmacology and Experimental Therapeutics
Cisplatin (CDDP) is a common, highly toxic chemotherapeutic agent. This study investigates chemoprotective effects of N-acetylcysteine (NAC) and sodium thiosulfate (STS) on in vitro and in vivo CDDP toxicities. For ototoxicity studies, CDDP (6 mg/kg) was administered to rats via a retrograde carotid artery infusion. Auditory brainstem response thresholds at 4 to 20 kHz were tested before and 7 days post-treatment. STS (8 g/m2 i.v.) was administered at 4, 8, or 12 h after CDDP. For… 

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Protection against cisplatin-induced ototoxicity by N-acetylcysteine in a rat model
Delayed administration of sodium thiosulfate in animal models reduces platinum ototoxicity without reduction of antitumor activity.
  • L. Muldoon, M. Pagel, E. Neuwelt
  • Biology, Medicine
    Clinical cancer research : an official journal of the American Association for Cancer Research
  • 2000
Delayed administration of sodium thiosulfate (STS) may provide a mechanism to reduce the ototoxicity caused by administration of carboplatin or cisplatin for both central nervous system and systemic cancer chemotherapy.
Therapeutic efficacy of aortic administration of N-acetylcysteine as a chemoprotectant against bone marrow toxicity after intracarotid administration of alkylators, with or without glutathione depletion in a rat model.
Surprisingly, aortic infusion of NAC to perfuse bone marrow and minimize myelosuppression and toxicity to visceral organs could be performed without interfering with the CNS cytotoxicity of intracarotid alkylators, even after BSO depletion of CNS glutathione.
In vitro and animal studies of sodium thiosulfate as a potential chemoprotectant against carboplatin-induced ototoxicity.
Delayed administration of sodium thiosulfate (STS) may provide a mechanism to reduce the cochlear toxicity caused by BBBD-enhanced carboplatin delivery to the brain.
Bone Marrow Chemoprotection without Compromise of Chemotherapy Efficacy in a Rat Brain Tumor Model
The data indicate the efficacy of enhanced chemotherapy for rat brain tumors was not affected by thiol chemoprotection that provided excellent protection for hematological toxicity.
The Chemoprotective Agent N-Acetylcysteine Blocks Cisplatin-Induced Apoptosis through Caspase Signaling Pathway
Results show that NAC blocks both the death receptor and the mitochondrial apoptotic pathways induced by cisplatin, and provides an opportunity to manipulate route and timing to maintain cisPlatin antitumor efficacy while protecting against chemotherapy side effects.
Tiopronin protects against the nephrotoxicity of cisplatin in the rat
Oral administration of tiopronin may be a clinically useful way to prevent cisplatin nephrotoxic effects in rats in vivo, and the results show that tiopronsin protects against cis platin-induced neph rotoxicity.
Cisplatin nephrotoxicity: site of functional disturbance and correlation to loss of body weight.
It is indicated that luminal (glucose and sulfate) and contraluminal (PAH) transport processes are affected by cisplatin and that contralumsinal transport (sulfate) can be unaffected or less affected than luminal transport processes (SF).