Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats

Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to...

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Published in:	Toxicology and applied pharmacology Vol. 279; no. 3; pp. 428 - 440
Main Authors:	Srivastava, Pranay, Yadav, Rajesh S., Chandravanshi, Lalit P., Shukla, Rajendra K., Dhuriya, Yogesh K., Chauhan, Lalit K.S., Dwivedi, Hari N., Pant, Aditiya B., Khanna, Vinay K.
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier Inc 15-09-2014 Elsevier
Subjects:	60 APPLIED LIFE SCIENCES Animals APOPTOSIS Apoptosis - drug effects Apoptosis Regulatory Proteins - genetics Apoptosis Regulatory Proteins - metabolism ARSENIC Arsenic Poisoning - metabolism Arsenic Poisoning - prevention & control Autonomic Nervous System Diseases - chemically induced Autonomic Nervous System Diseases - metabolism Autonomic Nervous System Diseases - prevention & control Biological and medical sciences Brain - pathology Brain - ultrastructure Brain Chemistry - drug effects Brain Chemistry - genetics Carcinogenesis, carcinogens and anticarcinogens Chemical agents Chemical and industrial products toxicology. Toxic occupational diseases CURCUMIN Curcumin - pharmacology GENES HIPPOCAMPUS Hippocampus - metabolism Hippocampus - pathology Hippocampus - ultrastructure Male Medical sciences Membrane Potential, Mitochondrial - drug effects Metals and various inorganic compounds Microscopy, Electron, Transmission MITOCHONDRIA Mitochondria - drug effects Mitochondria - metabolism Mitochondria - ultrastructure Mitochondrial damage MYELIN Neuroprotection Neuroprotective Agents - pharmacology Prefrontal Cortex - metabolism Prefrontal Cortex - pathology Prefrontal Cortex - ultrastructure Rat brain RATS Rats, Wistar Reactive Oxygen Species - metabolism Real-Time Polymerase Chain Reaction RECEPTORS Receptors, Muscarinic - metabolism Toxicology TRANSMISSION ELECTRON MICROSCOPY Tumors ULTRASTRUCTURAL CHANGES WEIGHT Neuroprotection Curcumin Arsenic Rat brain Mitochondrial damage Apoptosis Rat Tyrosine kinase inhibitor Rodentia Central nervous system Encephalon Carcinogen Vertebrata Mitochondria Polyphenol Mammalia Cell death Dysfunction Animal Phenols Lesion Mechanism of action
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Summary:	Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20mg/kg body weight, p.o) for 28days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20mg/kg body weight, p.o) and curcumin (100mg/kg body weight, p.o) for 28days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. •Neuroprotective mechanism of curcumin in arsenic induced cholinergic deficits studied•Curcumin protected arsenic induced enhanced expression of stress markers in rat brain•Arsenic compromised mitochondrial electron transport chain protected by curcumin•Functional and structural changes in mitochondria by arsenic protected by curcumin
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0041-008X 1096-0333
DOI:	10.1016/j.taap.2014.06.006