Acamprosate Modulates Alcohol-Induced Hippocampal NMDA Receptors and Brain Microsomal Ca2+-ATPase but Induces Oxidative Stress in Rat (original) (raw)

Abstract

We investigated the effects of acamprosate on alcohol-induced oxidative toxicity, microsomal membrane Ca2+-ATPase (MMCA) activity and _N_-methyl-d-aspartate receptor (NMDAR) subunits in rat brain. Forty male rats were equally divided into four groups. The first group was used as control, and the second group received ethanol. Acamprosate and acamprosate plus ethanol each day were administered to rats constituting the third and fourth groups for 21 days, respectively. Brain cortical and hippocampal samples were taken from the four groups after 21 days. Brain cortical lipid peroxidation (LP) levels and MMCA activity were higher in the alcohol group than in control, although glutathione peroxidase (GSH-Px), vitamin C, vitamin E and β-carotene values were lower in the alcohol group than in control. LP levels were further increased in the acamprosate and alcohol + acamprosate groups compared with the alcohol group. GSH-Px, vitamin A, vitamin C, vitamin E and β-carotene in the acamprosate and alcohol + acamprosate groups were further decreased compared with the alcohol group. Hippocampal NMDAR 2A and 2B subunit concentrations were lower in the alcohol group than in control, although they were increased by acamprosate and alcohol + acamprosate. Brain cortical MMCA activity was higher in the acamprosate group than in the alcohol-treated rats, although its activity was lower in the alcohol + acamprosate group than in the acamprosate group. Brain cortical reduced glutathione levels were not found to be statistically different in any of the groups. Oxidative stress has been proposed to explain the biological side effects of experimental alcohol intake. Acamprosate and alcohol-induced oxidative stress decreased brain antioxidant vitamins in the alcoholic rats.

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Abbreviations

CAT:

Catalase

GABA:

γ-Aminobutyric acid

GSH:

Reduced glutathione

GSH-Px:

Glutathione peroxidase

LP:

Lipid peroxidation

MDA:

Malondialdehyde

MMCA:

Microsomal membrane Ca2+-ATPase

NR2A:

anti-glutamate receptor NMDAR2A′

NR2B:

anti-glutamate receptor NMDAR2B

PUFAs:

Polyunsaturated fatty acids

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

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Acknowledgments

M. N. and R. Ö. formulated the present hypothesis and were responsible for writing the report. A. M. Ç., A. C. U., İ. S. Ö., R. S. and S. Ç. were responsible for analysis of the data. R. B. made critical revision to the manuscript. The study was partially supported by the Scientific Research Project Unit of Suleyman Demirel University (BAP-TU-09). Abstract of the study was submitted in 22th National Turkish Biophysics Society Congress, Aydin, Turkey.

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Authors and Affiliations

1. Department of Physiciatry, Medical Faculty, Süleyman Demirel University, Isparta, Turkey
   Ali Metehan Çalışkan, Sıla Çalışkan & Ramazan Özcankaya
2. Department of Biophysics, Medical Faculty, Süleyman Demirel University, Isparta, Turkey
   Mustafa Nazıroğlu, Abdulhadi Cihangir Uğuz & İshak Suat Övey
3. Neuroscience Research Center (NOROBAM), Süleyman Demirel University, Isparta, Turkey
   Mustafa Nazıroğlu
4. Department of Biochemistry, Medical Faculty, Süleyman Demirel University, Isparta, Turkey
   Recep Sütçü
5. Department of Physiology, Medical Faculty, Firat University, Elazığ, Turkey
   Ramazan Bal
6. Department of Cell Physiology and Pharmacology, Faculty of Medicine and Biological Sciences, Maurice Shock Medical Sciences Building, University Road, Leicester, LE1 9HN, UK
   Mustafa Nazıroğlu

Authors

1. Ali Metehan Çalışkan
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2. Mustafa Nazıroğlu
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3. Abdulhadi Cihangir Uğuz
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4. İshak Suat Övey
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5. Recep Sütçü
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6. Ramazan Bal
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7. Sıla Çalışkan
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8. Ramazan Özcankaya
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Correspondence toMustafa Nazıroğlu.

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Çalışkan, A.M., Nazıroğlu, M., Uğuz, A.C. et al. Acamprosate Modulates Alcohol-Induced Hippocampal NMDA Receptors and Brain Microsomal Ca2+-ATPase but Induces Oxidative Stress in Rat.J Membrane Biol 237, 51–58 (2010). https://doi.org/10.1007/s00232-010-9305-y

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• Received: 25 July 2010
• Accepted: 02 September 2010
• Published: 25 September 2010
• Issue Date: September 2010
• DOI: https://doi.org/10.1007/s00232-010-9305-y

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