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N-Acetyl-L-cysteine Affects Ototoxicity Evoked by Amikacin and Furosemide Either Alone or in Combination in a Mouse
Marek Zadrożniak1, Marcin Szymański1, Jarogniew J Łuszczki2
1Department of Otolaryngology and Laryngological Oncology, Medical University of Lublin, 20-090 Lublin, Poland.
Abstract:
Drug-induced ototoxicity resulting from therapy with aminoglycoside antibiotics and loop diuretics is one of the main well-known causes of hearing loss in patients. Unfortunately, no specific protection and prevention from hearing loss are recommended for these patients. This study aimed at evaluating the ototoxic effects produced by mixtures of amikacin (AMI, an aminoglycoside antibiotic) and furosemide (FUR, a loop diuretic) in the mouse model as the hearing threshold decreased by 20% and 50% using auditory brainstem responses (ABRs). Ototoxicity was produced by the combinations of a constant dose of AMI (500 mg/kg; i.p.) on FUR-induced hearing threshold decreases, and a fixed dose of FUR (30 mg/kg; i.p.) on AMI-induced hearing threshold decreases, which were determined in two sets of experiments. Additionally, the effects of N-acetyl-L-cysteine (NAC; 500 mg/kg; i.p.) on the hearing threshold decrease of 20% and 50% were determined by means of an isobolographic transformation of interactions to detect the otoprotective action of NAC in mice. The results indicate that the influence of a constant dose of AMI on FUR-induced hearing threshold decreases was more ototoxic in experimental mice than a fixed dose of FUR on AMI-induced ototoxicity. Moreover, NAC reversed the AMI-induced, but not FUR-induced, hearing threshold decreases in this mouse model of hearing loss. NAC could be considered an otoprotectant in the prevention of hearing loss in patients receiving AMI alone and in combination with FUR.
Insights
Aminoglycoside antibiotics and loop diuretics cause hearing loss. N-acetyl-L-cysteine (NAC) protected against amikacin-induced ototoxicity, but not furosemide-induced ototoxicity, in mice.
Area of Science:
- Ototoxicology
- Pharmacology
- Auditory Neuroscience
Background:
- Drug-induced ototoxicity from aminoglycosides and loop diuretics is a significant cause of hearing loss.
- Current preventative measures for this hearing loss are limited.
- Aminoglycoside antibiotics (e.g., amikacin) and loop diuretics (e.g., furosemide) are common culprits.
Purpose of the Study:
- To evaluate the ototoxic effects of combined amikacin (AMI) and furosemide (FUR) in a mouse model.
- To assess the potential otoprotective effects of N-acetyl-L-cysteine (NAC) against drug-induced hearing loss.
Main Methods:
- Auditory brainstem responses (ABRs) were used to measure hearing thresholds in mice.
- Ototoxicity was induced by fixed doses of AMI combined with varying doses of FUR, and vice versa.
- N-acetyl-L-cysteine (NAC) was administered to evaluate its protective effects using isobolographic analysis.
Main Results:
- Amikacin demonstrated greater ototoxicity when combined with furosemide compared to furosemide combined with amikacin.
- N-acetyl-L-cysteine (NAC) significantly reversed amikacin-induced hearing threshold decreases.
- NAC did not show a protective effect against furosemide-induced hearing threshold decreases.
Conclusions:
- Amikacin's ototoxic impact is potentiated by furosemide.
- N-acetyl-L-cysteine (NAC) shows promise as an otoprotectant against amikacin-induced hearing loss.
- NAC may help prevent hearing loss in patients treated with amikacin, alone or in combination with furosemide.
