A comparison of the protective effects of systemic administration of a pro-glutathione drug and a Src-PTK inhibitor against noise-induced hearing loss.
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.
Bielefeld
Eric C
EC
Center for Hearing and Deafness, Department of Communicative Disorders and Sciences, State University of New York at Buffalo, Buffalo, NY 14214, USA. ecb2@buffalo.edu
Hynes
Sarah
S
Pryznosch
David
D
Liu
Jianzhong
J
Coleman
John Km
JK
Henderson
Donald
D
D000111:Acetylcysteine / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001309:Auditory Threshold / Q000187:drug effects; D002682:Chinchilla; D004195:Disease Models, Animal; D004566:Electrodes; D004781:Environmental Exposure / Q000009:adverse effects; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D005978:Glutathione / Q000008:administration & dosage* / Q000494:pharmacology; D006317:Hearing Loss, Noise-Induced / Q000188:drug therapy / Q000517:prevention & control*; D007245:Inferior Colliculi / Q000502:physiology; D007274:Injections, Intraperitoneal; D009622:Noise / Q000009:adverse effects*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000009:adverse effects*; D013997:Time Factors; D019061:src-Family Kinases / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D019061:src-Family Kinases; D005978:Glutathione; D000111:Acetylcysteine