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

Abstract

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.

• Authors: Eric C Bielefeld, Sarah Hynes, David Pryznosch, Jianzhong Liu, John Km Coleman, Donald Henderson
• Journal: Noise & health (Noise Health) 2005 Oct-Dec Vol. 7 Issue 29 Pg. 24-30 ISSN: 1463-1741 [Print] India
• PMID: 17478966 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Protein Kinase Inhibitors
• Reactive Oxygen Species
• src-Family Kinases
• Glutathione
• Acetylcysteine

Topics

• Acetylcysteine (administration & dosage, pharmacology)
• Animals
• Apoptosis (drug effects)
• Auditory Threshold (drug effects)
• Chinchilla
• Disease Models, Animal
• Electrodes
• Environmental Exposure (adverse effects)
• Evoked Potentials, Auditory (drug effects)
• Glutathione (administration & dosage, pharmacology)
• Hearing Loss, Noise-Induced (drug therapy, prevention & control)
• Inferior Colliculi (physiology)
• Injections, Intraperitoneal
• Noise (adverse effects)
• Protein Kinase Inhibitors (administration & dosage, pharmacology)
• Reactive Oxygen Species (adverse effects)
• Time Factors
• src-Family Kinases (administration & dosage, antagonists & inhibitors, pharmacology)