Neuroprotective effect of ACE inhibitors in glutamate - induced neurotoxicity: rat neuron culture study

Turk Neurosurg. 2011;21(3):367-71. doi: 10.5137/1019-5149.JTN.4313-11.0.

Abstract

Aim: Glutamate is known to be neurotoxic at concentrations of 10-6M and 10-7M. Angiotensin converting enzyme (ACE) inhibitors can be assumed to be neuroprotective as they open the mitochondrial adenosine triphosphate-sensitive potassium channels by inhibiting the degradation of bradykinin. In this study, we investigated whether the ACE inhibitors captopril, ramipril and perindopril have protective effects in glutamate-induced neurotoxicity in newborn rat cerebral cortex cell cultures.

Material and methods: Viability tests were performed among ACE inhibitors by constituting groups of control and 10-7M and 10-6M glutamate doses in newborn rat cortex cultures.

Results: While the mean viable cell number was 0.47±0.06 in the control group, it was 0.37±0.03 in the group exposed to 10-7M glutamate (p < 0.05) and 0.37±0.01 in the group exposed to 10-6M glutamate (p < 0.05). Captopril was used at a dose of 10 μM, perindopril was used at a dose of 1 μM, and ramipril was used at a dose of 30 μM against 10-7M and 10-6M glutamate. Ramipril and perindopril reversed the toxicity against 10-6M glutamate (p < 0.05). The neuroprotective properties of captopril, perindopril and ramipril were not found to be statistically significant against 10-7M glutamate at the doses mentioned above.

Conclusion: Data obtained from this study indicate that ramipril and perindopril can prevent 10-6M glutamate-induced neurotoxicity.

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Animals, Newborn
  • Captopril / pharmacology
  • Cell Survival / drug effects
  • Cells, Cultured
  • Glutamic Acid / toxicity*
  • Neurons / drug effects*
  • Neuroprotective Agents*
  • Neurotoxicity Syndromes / prevention & control*
  • Perindopril / pharmacology
  • Ramipril / pharmacology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Neuroprotective Agents
  • Glutamic Acid
  • Captopril
  • Ramipril
  • Perindopril