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

Noise Health. 2005 Oct-Dec;7(29):24-30. doi: 10.4103/1463-1741.31875.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylcysteine / administration & dosage*
  • Acetylcysteine / 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*
  • Glutathione / pharmacology
  • Hearing Loss, Noise-Induced / drug therapy
  • Hearing Loss, Noise-Induced / prevention & control*
  • Inferior Colliculi / physiology
  • Injections, Intraperitoneal
  • Noise / adverse effects*
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / pharmacology
  • Reactive Oxygen Species / adverse effects*
  • Time Factors
  • src-Family Kinases / administration & dosage
  • src-Family Kinases / antagonists & inhibitors*
  • src-Family Kinases / pharmacology

Substances

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