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EFFECTIVNESS OF CREATINE AND CYCLOSPORINE TO PROTECT AGAINST PROPIONIC ACID- INDUCED NEUROTOXICITY. El-Ansary A., Nounou HA, Abdelzaher E

EFFECTIVNESS OF CREATINE AND CYCLOSPORINE TO PROTECT AGAINST PROPIONIC ACID- INDUCED NEUROTOXICITY.

El-Ansary A., Nounou H. A., Abdelzaher E.

International Journal of Pharmacology & Toxicology Science 2011; 2: 28-43

Abstract

Objectives: This work aims to study the neuroprotective effect of creatine and cyclosporine in ameliorating the neurotoxic effects of orally administrated propionic acid to young rats.
Methods: Young male rats (n= 32) were divided into four groups; oral buffered propionic acid - treated group, cyclosporine and creatine protected groups followed by propionic acid. A fourth control group. Reduced glutathione, malondialdehyde, vitamin C, catalase and Comet DNA were assayed in brain homogenates.
Results: It was observed that propionic acid caused brain degeneration as measured by reduced glutathione and vitamin C depletion together with the increase of malondialdehyde as a marker of oxidative stress. Decreased lactate oxidase activity in brain homogenates of propionic acid-treated rats was attributed to the leakage of the enzyme from brain, while increase of creatine kinase activity suggested a compensatory mechanism to overcome ATP depletion. In addition, propionic acid induced DNA strand breaks. Creatine administration prior to propionic acid treatment was greatly protective showing elevated reduced glutathione and vitamin C levels, decreased lipid peroxidation and lactate oxidase release from brain to plasma, and DNA damage. On the other hand, cyclosporine treatment was less protective compared to creatine. Moreover histopathological examination showed neural loss which is considered as a neurotoxic marker in propionic acid treated group. Creatine and cyclosprine showed high efficacy in ameliorating the induced pathological changes.
Conclusion: These findings prove that propionic induced brain degeneration in young rats and confirm the protective efficacy of creatine as a nutritional supplement could be used to treat early diagnosed patients with autism, a disease related to propionic acid neurotoxicity.

Key words: Autism, DNA damage, Oxidative stress, Propionic acid, creatine and cyclosporine.
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