Dose and Time-dependent Alterations in Various Cholinergic and Non-cholinergic Markers after Organophosphate Poisoning: Possible Role in Diagnosis

  • Jebin Jacob John Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior
  • Niranjan L Gujar Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior
  • G B.K.S Prasad School of Studies in Biochemistry, Jiwaji University, Gwalior
  • Rahul Bhattacharya Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior
Keywords: Organophosphate, DFP, acute toxicity, cholinergic and non-cholinergic markers, oxidative stress, DNA damage

Abstract

Toxicity of organophosphates (OP) is mainly ascribed to inhibition of acetylcholinesterase (AChE) enzyme at the cholinergic synapses. This results in cholinergic crisis leading to various muscarinic, nicotinic and central effects. Additionally, there are several non-cholinergic effects of OP which are likely to exacerbate the toxicity and complicate diagnosis. The present study reports the dose (0.125 - 4.0 LD50) and time (1 h - 14 d)- dependent acute effect of diisopropyl phosphorofluoridate (DFP) on mice body weight, organ-body weight index (brain), butyrylcholinesterase (BChE) and β-glucoronidase (BG) activity in plasma, AChE activity, reduced glutathione (GSH) and malondialdehyde (MDA) levels in brain, and DNA damage in brain (agarose gel electrophoresis) and blood (comet assay). The study reveals a dose and time- dependent BChE inhibition up to 24 h and AChE inhibition up to 7 d. However, elevated BG levels were observed up to 1 h only after 1.0, 2.0, and 4.0 LD50 DFP. Diminished GSH levels up to 24 h and increased MDA levels at 4 h indicated oxidative stress. None of the treatments produced any DNA damage in soft tissues. In addition to cholinesterase, the study suggests possible relevance of measuring BG levels (non-cholinergic marker) in the diagnosis of OP poisoning.

Author Biographies

Jebin Jacob John, Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior
Mr Jebin Jacob John received his MSc (Biotechnology) from Sardar Patel University, Anand in 2012. He is presently working as DRDO-JRF in the Division of Pharmacology & Toxicology, DRDE, Gwalior. He contributed towards experimental execution and tabulation of data.
Niranjan L Gujar, Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior
Mr Niranjan L Gujar received his MSc (Biochemistry) from North Maharashtra University, Jalgaon in 1998. He is presently working as Technical Officer ‘A’ in the Division of Pharmacology & Toxicology, DRDE, Gwalior. He has 06 research papers and 01 patent to his credit. He contributed towards animal preparation and experimental execution
G B.K.S Prasad, School of Studies in Biochemistry, Jiwaji University, Gwalior
Dr G.B.K.S. Prasad is Professor and Head, School of Studies in Biochemistry, Jiwaji University, Gwalior. He has more than 100 research papers in peer reviewed national and international journals, 03 book chapters, and 03 books to his credit. He contributed towards experimental planning and technical advice
Rahul Bhattacharya, Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior
Dr Rahul Bhattacharya is Scientist ‘G’ in the Division of Pharmacology & Toxicology, DRDE, Gwalior. He has more than 80 research papers in peer reviewed national and international journals, 08 book chapters, and 05 patents and copyrights to his credit. He contributed towards experimental planning, execution, data analysis and writing of the manuscript.
Published
2016-10-07
How to Cite
JohnJ., GujarN., PrasadG., & BhattacharyaR. (2016). Dose and Time-dependent Alterations in Various Cholinergic and Non-cholinergic Markers after Organophosphate Poisoning: Possible Role in Diagnosis. Defence Life Science Journal, 1(2), 171-178. https://doi.org/10.14429/dlsj.1.10746
Section
Research Article