title: Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats.
abstract: 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 28 days 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 28 days 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.
authors: CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001, India.
authors: Pranay
authors: P
authors: Srivastava
authors: CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001, India; Department of Crimnology and Forensic Science, Harisingh Gour University, Sagar 470 003, India.
authors: Rajesh S
authors: RS
authors: Yadav
authors: CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001, India.
authors: Lalit P
authors: LP
authors: Chandravanshi
authors: CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001, India.
authors: Rajendra K
authors: RK
authors: Shukla
authors: CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001, India.
authors: Yogesh K
authors: YK
authors: Dhuriya
authors: CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001, India.
authors: Lalit K S
authors: LKS
authors: Chauhan
authors: Babu Banarasi Das University, BBD City, Faizabad Road, Lucknow 227 015, India.
authors: Hari N
authors: HN
authors: Dwivedi
authors: CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001, India.
authors: Aditiya B
authors: AB
authors: Pant
authors: CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001, India. Electronic address: vkkhanna1@gmail.com.
authors: Vinay K
authors: VK
authors: Khanna
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D020261:Arsenic Poisoning / Q000378:metabolism / Q000517:prevention & control*; D001342:Autonomic Nervous System Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D001921:Brain / Q000473:pathology / Q000648:ultrastructure; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics; D003474:Curcumin / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011976:Receptors, Muscarinic / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D011976:Receptors, Muscarinic; D003474:Curcumin
keywords: Apoptosis; Arsenic; Curcumin; Mitochondrial damage; Neuroprotection; Rat brain