Vinpocetine protects from aminoglycoside antibiotic-induced hearing loss in guinea pig in vivo

Brain Res. 2000 Jun 23;868(2):222-9. doi: 10.1016/s0006-8993(00)02333-7.

Abstract

The principal objective of this study is to explore the hypothesis that a blockade of Na(+) channels can prevent some of the mechanisms involved in ototoxicity. For this purpose, the potential action of the voltage sensitive Na(+) channel antagonist, vinpocetine, on the ototoxicity induced by the representative aminoglycoside antibiotic, amikacin, in guinea pigs was tested for almost half a year. Amikacin (450 mg/kg) administered daily (i.m.) for 5 days increases the thresholds of the auditory brainstem response (ABR) to the two frequencies tested (4 and 8 kHz). These threshold increases are permanent or at least long-lived, as after 40 days they are already established and are maintained until the end of the experiment (160 days after the antibiotic administration). Amikacin decreases the amplitude of ABR waves, particularly P1, and after 160 days increases the latency of ABR waves, particularly at the higher frequency tested (8 kHz). When the above amikacin regimen is followed by a daily (i.p.) vinpocetine (2 mg/kg) administration for 13 days the increase in ABR threshold and latency caused by amikacin alone is prevented. Moreover, the animals treated with amikacin alone show a decreased weight gain and a remarkable increased mortality in comparison with the group of animals post-treated with vinpocetine. We hope that the multiple beneficial effects exerted by the Na(+) channel blocker, vinpocetine, against aminoglycoside antibiotics-induced side effects could help to solve the serious limitations of the use of this type of antibiotic.

MeSH terms

  • Amikacin / adverse effects
  • Animals
  • Anti-Bacterial Agents / adverse effects*
  • Auditory Pathways / drug effects*
  • Auditory Pathways / physiology
  • Auditory Threshold / drug effects
  • Auditory Threshold / physiology
  • Deafness / chemically induced*
  • Deafness / physiopathology
  • Deafness / prevention & control*
  • Evoked Potentials, Auditory, Brain Stem / drug effects
  • Evoked Potentials, Auditory, Brain Stem / physiology
  • Guinea Pigs
  • Male
  • Neuroprotective Agents / pharmacology*
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Sodium Channel Blockers*
  • Sodium Channels / drug effects
  • Sodium Channels / metabolism
  • Survival Rate
  • Vinca Alkaloids / pharmacology*
  • Weight Gain / drug effects
  • Weight Gain / physiology

Substances

  • Anti-Bacterial Agents
  • Neuroprotective Agents
  • Sodium Channel Blockers
  • Sodium Channels
  • Vinca Alkaloids
  • vinpocetine
  • Amikacin