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[An experimental study of ototoxicity induced by deferoxamine mesilate]
1Fukushima Medical University.
Abstract:
We investigated the possibility of ototoxicity induced by deferoxamine mesilate (DFO). DFO was administered to guinea pigs intraperitoneally at 200 or 400 mg/kg body weight/day, 6 days/week for 5 weeks, or 600 mg/kg body weight/day, 6 days/week for 4 weeks. Physiological saline instead of DFO was given to animals as a control. After the course of administration was completed, we measured the threshold of the compound action potential (CAP) and the endocochlear potential (EP). We also examined the cochlear histology by scanning electron microscopy. The CAP threshold of animals treated with 200 or 400 mg of DFO per kg was not elevated. In the animals treated with 600 mg/kg , however, the CAP threshold was clearly elevated when compared with that of control animals. The EP values of animals treated with 200 or 400 mg of DFO per kg were comparable to those of control animals. In some animals treated with 600 mg of DFO per kg, however, the EP values were decreased. Histological examination revealed that the outer hair cells of the cochlea were missing. DFO presumably acts on hair cells, resulting in elevation of the CAP threshold. We concluded that hair cell damage is one of the contributing factors to CAP threshold elevation.
Insights
Deferoxamine mesilate (DFO) may cause ototoxicity. High doses of DFO in guinea pigs led to elevated compound action potential thresholds and outer hair cell damage, indicating potential hearing loss risks.
Area of Science:
- Ototoxicology
- Pharmacology
- Neuroscience
Context:
- Deferoxamine mesilate (DFO) is a chelating agent used in treating iron overload.
- Potential side effects of DFO, including ototoxicity, require thorough investigation.
- Understanding drug-induced hearing loss is crucial for patient safety.
Purpose:
- To investigate the ototoxic potential of deferoxamine mesilate (DFO) in a guinea pig model.
- To assess the effects of DFO administration on auditory function and cochlear integrity.
- To determine the dose-dependent relationship between DFO exposure and hearing impairment.
Summary:
- Guinea pigs received varying doses of DFO (200, 400, or 600 mg/kg/day) or saline for several weeks.
- Auditory function was evaluated by measuring compound action potential (CAP) and endocochlear potential (EP) thresholds.
- Cochlear histology was examined using scanning electron microscopy to assess hair cell damage.
Impact:
- DFO administration at 600 mg/kg/day resulted in significantly elevated CAP thresholds and decreased EP values.
- Histological analysis revealed missing outer hair cells in the cochlea of animals treated with the highest DFO dose.
- DFO-induced hair cell damage is a contributing factor to elevated CAP thresholds, suggesting a risk of hearing loss with high-dose DFO treatment.