Protection by methylene blue against haloperidol-induced neuronal and liver damage
Keywords:
Haloperidol, Antipsychotic drugs, Methylene blue, Oxidative stress, Paraoxonase-1, B-cell leukemia/lymphoma 2, Neurotoxicity
Abstract
Haloperidol is a first-generation antipsychotic that induces oxidative stress and neuronal injury. The objective of this study was to examine the effect of the redox dye methylene blue (MethyB) on brain oxidative stress and neurodegeneration and on liver tissue damage in the rat after acute administration of high dose haloperidol. Rats were orally treated with haloperidol at a dose of 5 mg/kg alone or co-administered with MethyB at doses of 1, 5, 10, 20 mg/kg, intraperitoneally daily for two days. Biomarkers of oxidative stress including lipid peroxidation (malondialdehyde), nitric oxide, reduced glutathione, paraoxonase-1 activity (PON-1) and the level of the anti-apoptotic protein Bcl-2 were determined. Histopathological examination of brain and liver tissue was also done. Haloperidol treatment resulted in significant increases in malondialdehyde and nitric oxide compared with the vehicle group. Significant decreases were also observed in reduced glutathione, PON-1 activity and Bcl-2. Treatment with MethyB prevented the increase in lipid peroxidation and nitric oxide and restored PON-1 activity in a dose-dependent manner. Haloperidol resulted in spongiform changes, dead neurons in the cerebral cortex and degeneration of Purkinje cells and white matter vacuolation in cerebellum. The drug also caused distortion of liver architecture, massive vacuolation, necrosis and pyknosis of hepatocytes. These pathological changes were alleviated to great extent by MethyB at 20 mg/kg. Our findings suggest that oxidative stress is involved in the neurotoxic effects of high dose haloperidol and that MethyB affords protection. This protective action of MethyB involves decreased oxidative stress.
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Published
2020-06-19
How to Cite
Abdel-Salam, O. M., Sleem, A. A., Youness, E. R., & Morsy, F. A. (2020). Protection by methylene blue against haloperidol-induced neuronal and liver damage. Journal of Basic Pharmacology and Toxicology, 4(1), 17-27. Retrieved from https://www.scigreen.com/index.php/JBPT/article/view/67
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Section
Original Research Articles
Copyright (c) 2020 Omar Abdel-Salam, Amany Sleem, Eman Youness, Fata Morsy

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© The Authors. Published by SciGreen Publications. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).