A comparison of the protective effects of systemic administration of a pro-glutathione drug and a Src-PTK inhibitor against noise-induced hearing loss

• Published in: Noise & health Vol. 7; no. 29; pp. 24 - 30
• Main Authors: Bielefeld, Eric C, Hynes, Sarah, Pryznosch, David, Liu, Jianzhong, Coleman, John Km, Henderson, Donald
• Format: Journal Article
• Language: English
• Published: India Medknow Publications and Media Pvt. Ltd 01-10-2005; Medknow Publications & Media Pvt. Ltd
• Subjects: Acetylcysteine - administration & dosage; Acetylcysteine - pharmacology; Animals; Antioxidants; Apoptosis; Apoptosis - drug effects; Auditory Threshold - drug effects; Chinchilla; Deafness, Noise induced; Disease Models, Animal; Dosage and administration; Drug dosages; Drug therapy; Electrodes; Environmental Exposure - adverse effects; Evoked Potentials, Auditory - drug effects; Free radicals; Glutathione - administration & dosage; Glutathione - pharmacology; Hearing loss; Hearing Loss, Noise-Induced - drug therapy; Hearing Loss, Noise-Induced - prevention & control; Hearing protection; Inferior Colliculi - physiology; Injections, Intraperitoneal; Kinases; Noise; Noise - adverse effects; Pharmaceutical research; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - pharmacology; Reactive Oxygen Species - adverse effects; src-Family Kinases - administration & dosage; src-Family Kinases - antagonists & inhibitors; src-Family Kinases - pharmacology; Studies; Time Factors; United States
• ISSN: 1463-1741; 1998-4030
• DOI: 10.4103/1463-1741.31875

Both the antioxidant, n-l-acetyl cysteine (L-NAC) and the Src inhibitor, KX1-004, have been used to protect the cochlea from hazardous noise. To date, KX1-004 has only been used locally on the round window. In the current study, the two drugs were administered systemically. LNAC was delivered intraperitoneally at a dose of 325 mg/kg while KX1-004 was administered subcutaneously at a dose of 50 mg/kg. The noise exposure consisted of a 4 kHz octave band of noise at 100 dB SPL for 6 hours/day for 4 days. The drugs were administered once each day, 30 minutes prior to the onset of the noise exposure. The animals' hearing was estimated using the evoked response records from surgically-implanted chronic electrodes in the inferior colliculi. Animals treated with LNAC and KX1-004 had from 10 to 20 dB less temporary threshold shift at day 1 and an average 10 dB less permanent threshold shift by day 21 when compared to control saline treated animals. There were no significant side effects (i.e.: appetite loss, weight loss, lethargy, etc.) related to either of the drug treatments. KX1-004 produced at least as much protection as L-NAC, but at a significantly lower concentration.