Acetyl-l-carnitine protects neuronal function from alcohol-induced oxidative damage in the brain

Travis J. Rump, P. M.Abdul Muneer, Adam M. Szlachetka, Allyson Lamb, Catherine Haorei, Saleena Alikunju, Huangui Xiong, James Keblesh, Jianuo Liu, Matthew C. Zimmerman, Jocelyn Jones, Terrence M. Donohue, Yuri Persidsky, James Haorah

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

The studies presented here demonstrate the protective effect of acetyl- l-carnitine (ALC) against alcohol-induced oxidative neuroinflammation, neuronal degeneration, and impaired neurotransmission. Our findings reveal the cellular and biochemical mechanisms of alcohol-induced oxidative damage in various types of brain cells. Chronic ethanol administration to mice caused an increase in inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine adduct formation in frontal cortical neurons but not in astrocytes from brains of these animals. Interestingly, alcohol administration caused a rather selective activation of NADPH oxidase (NOX), which, in turn, enhanced levels of reactive oxygen species (ROS) and 4-hydroxynonenal, but these were predominantly localized in astrocytes and microglia. Oxidative damage in glial cells was accompanied by their pronounced activation (astrogliosis) and coincident neuronal loss, suggesting that inflammation in glial cells caused neuronal degeneration. Immunohistochemistry studies indicated that alcohol consumption induced different oxidative mediators in different brain cell types. Thus, nitric oxide was mostly detected in iNOS-expressing neurons, whereas ROS were predominantly generated in NOX-expressing glial cells after alcohol ingestion. Assessment of neuronal activity in ex vivo frontal cortical brain tissue slices from ethanol-fed mice showed a reduction in long-term potentiation synaptic transmission compared with slices from controls. Coadministration of ALC with alcohol showed a significant reduction in oxidative damage and neuronal loss and a restoration of synaptic neurotransmission in this brain region, suggesting that ALC protects brain cells from ethanol-induced oxidative injury. These findings suggest the potential clinical utility of ALC as a neuroprotective agent that prevents alcohol-induced brain damage and development of neurological disorders.

Original languageEnglish (US)
Pages (from-to)1494-1504
Number of pages11
JournalFree Radical Biology and Medicine
Volume49
Issue number10
DOIs
StatePublished - Nov 30 2010

Fingerprint

Acetylcarnitine
Carnitine
Brain
Alcohols
Synaptic Transmission
Neuroglia
Ethanol
NADPH Oxidase
Nitric Oxide Synthase Type II
Astrocytes
Neurons
Reactive Oxygen Species
Chemical activation
Long-Term Potentiation
Microglia
Neuroprotective Agents
Nervous System Diseases
Alcohol Drinking
Restoration
Nitric Oxide

All Science Journal Classification (ASJC) codes

  • Physiology (medical)
  • Biochemistry

Keywords

  • Acetyl-l-carnitine
  • Alcohol-induced oxidative damage
  • Astrogliosis
  • Free radicals
  • Neurodegeneration
  • Synaptic neurotransmission

Cite this

Rump, Travis J. ; Muneer, P. M.Abdul ; Szlachetka, Adam M. ; Lamb, Allyson ; Haorei, Catherine ; Alikunju, Saleena ; Xiong, Huangui ; Keblesh, James ; Liu, Jianuo ; Zimmerman, Matthew C. ; Jones, Jocelyn ; Donohue, Terrence M. ; Persidsky, Yuri ; Haorah, James. / Acetyl-l-carnitine protects neuronal function from alcohol-induced oxidative damage in the brain. In: Free Radical Biology and Medicine. 2010 ; Vol. 49, No. 10. pp. 1494-1504.
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Rump, TJ, Muneer, PMA, Szlachetka, AM, Lamb, A, Haorei, C, Alikunju, S, Xiong, H, Keblesh, J, Liu, J, Zimmerman, MC, Jones, J, Donohue, TM, Persidsky, Y & Haorah, J 2010, 'Acetyl-l-carnitine protects neuronal function from alcohol-induced oxidative damage in the brain', Free Radical Biology and Medicine, vol. 49, no. 10, pp. 1494-1504. https://doi.org/10.1016/j.freeradbiomed.2010.08.011

Acetyl-l-carnitine protects neuronal function from alcohol-induced oxidative damage in the brain. / Rump, Travis J.; Muneer, P. M.Abdul; Szlachetka, Adam M.; Lamb, Allyson; Haorei, Catherine; Alikunju, Saleena; Xiong, Huangui; Keblesh, James; Liu, Jianuo; Zimmerman, Matthew C.; Jones, Jocelyn; Donohue, Terrence M.; Persidsky, Yuri; Haorah, James.

In: Free Radical Biology and Medicine, Vol. 49, No. 10, 30.11.2010, p. 1494-1504.

Research output: Contribution to journalArticle

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AU - Rump, Travis J.

AU - Muneer, P. M.Abdul

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AU - Lamb, Allyson

AU - Haorei, Catherine

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AU - Xiong, Huangui

AU - Keblesh, James

AU - Liu, Jianuo

AU - Zimmerman, Matthew C.

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AU - Donohue, Terrence M.

AU - Persidsky, Yuri

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