title: Plant toxin abrin induced oxidative stress mediated neurodegenerative changes in mice.
abstract: Abrin is a potent plant toxin. It is a heterodimeric protein toxin which is obtained from the seeds of Abrus precatorius plant. At cellular level abrin causes protein synthesis inhibition by removing the specific adenine residue (A4324) from the 28s rRNA of the 60S - ribosomal subunit. In the present study we investigated the role of oxidative stress in neurotoxic potential and demyelinating effects of abrin on brain. The mechanism by which abrin induces oxidative damage and toxicity in brain are relatively unknown. Animals were exposed to 0.4 and 1.0 LD50 abrin dose by intraperitoneal route and observed for 1 and 3 day post-toxin exposure. Oxidative stress occurred in brain due to abrin was confirmed in terms of increased reactive oxygen species (ROS), glutathione depletion and increased lipid peroxidation. Significant increase in blood and brain ROS was observed at day 3, 1 LD50. Abrin induced changes in the neurotransmitters (5-hydroxy tryptamine, norepinephrine, dopamine and monoamine oxidase) levels were evaluated by spectroflourometry. Increase in the levels of 5-HT and NE was observed after abrin exposure. MAO activity was found to be decreased in abrin exposed animals compared to control. Significant inhibition in the activity of acetylcholine esterase enzyme in brain and serum was reported for both the doses and time points. Western blot analysis of iNOS expression indicated that abrin treatment resulted in dose and time dependent increase. Furthermore, protein expression of myelin basic protein (MBP) was down regulated in a dose and time dependent manner. Brain histopathology was carried out and cortical brain region showed demyelination after abrin exposure. Results confirmed that abrin poisoning leads to neurodegeneration and neurotoxicity mediated through oxidative stress, AChE inhibition, lipid peroxidation and decrease in MBP levels.
authors.affiliation: Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, India. Electronic address: bhaskar@drde.drdo.in.
authors.forename: A S B
authors.initials: AS
authors.lastname: Bhasker
authors.affiliation: Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, India.
authors.forename: Bhavana
authors.initials: B
authors.lastname: Sant
authors.affiliation: Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, India.
authors.forename: Preeti
authors.initials: P
authors.lastname: Yadav
authors.affiliation: Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, India.
authors.forename: Mona
authors.initials: M
authors.lastname: Agrawal
authors.affiliation: DRDO-BU Center for Life Sciences, Bharathiar University, Coimbatore 641046, India.
authors.forename: P V
authors.initials: PV
authors.lastname: Lakshmana Rao
mesh_terms: D000036:Abrin / Q000633:toxicity*; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008995:Monoamine Oxidase / Q000378:metabolism; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects* / Q000473:pathology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011500:Protein Synthesis Inhibitors / Q000633:toxicity*; D017382:Reactive Oxygen Species
chemical_list: D015306:Biogenic Monoamines; D004676:Myelin Basic Protein; D011500:Protein Synthesis Inhibitors; D017382:Reactive Oxygen Species; D000036:Abrin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D008995:Monoamine Oxidase; D000110:Acetylcholinesterase
keywords: Abrin; Acetyl cholinesterase (AChE); Myelin basic protein (MBP); Neurotransmitters; Ribosome inactivating proteins (RIP)