Protection against cisplatin-induced ototoxicity by N-acetylcysteine in a rat model
| Autor: | Dale F. Kraemer, D. Thomas Dickey, Leslie L. Muldoon, Edward A. Neuwelt |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
inorganic chemicals
medicine.medical_treatment Antineoplastic Agents Pharmacology Drug Administration Schedule Acetylcysteine Ototoxicity medicine.artery medicine Evoked Potentials Auditory Brain Stem Animals Rats Long-Evans Ear Diseases Hearing Loss neoplasms Saline Cisplatin Aorta business.industry Body Weight medicine.disease female genital diseases and pregnancy complications Sensory Systems Rats Auditory brainstem response Anesthesia Toxicity Animal studies business medicine.drug |
| Zdroj: | Hearing research. 193(1-2) |
| ISSN: | 0378-5955 |
| Popis: | Cisplatin (CDDP) is a widely used chemotherapeutic agent that is highly ototoxic. Animal studies and clinical trials have shown that thiosulfates can protect against platinum-induced ototoxicity. This study investigated a new model for CDDP ototoxicity in the rat, and tested the potential chemoprotective effect of administering N-acetylcysteine (NAC) before giving CDDP. Long Evans rats were treated with CDDP 6 mg/kg delivered to the aorta via a retrograde right external carotid artery infusion, 15 min after intravenous (IV) infusion of saline (n=8) or NAC 400 mg/kg (n=8), such that the vertebral arteries were perfused. Subsequent groups were similarly treated with NAC 30 min before (n=7) and 4 h after (n=7) CDDP. Auditory brainstem response (ABR) thresholds were tested at 4-20 kHz, 7 days after treatment and compared to baseline ABR values. The NAC-treated rats exhibited no significant change from baseline values at all time intervals, while the saline-treated rats showed marked ototoxicity, especially at higher frequencies. Furthermore, the rats treated with NAC 15 min before CDDP exhibited less overall toxicity to CDDP, as evidenced in weight loss 7 days post-treatment (mean for saline=-39.63 g; mean for NAC=-21.13 g; p=0.0084). These data show that treatment with NAC can prevent CDDP-induced ototoxicity in rats. |
| Databáze: | OpenAIRE |
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