Theses and Dissertations

Issuing Body

Mississippi State University

Advisor

Chambers, Janice E.

Committee Member

Ross, Matthew K.

Committee Member

Mlsna, Todd E.

Date of Degree

8-7-2020

Original embargo terms

Visible to MSU only for 2 years

Document Type

Graduate Thesis - Open Access

Major

Environmental Toxicology

Degree Name

Master of Science

Degree Name

Master of Science (M.S.)

College

College of Veterinary Medicine

College

College of Veterinary Medicine

Department

Department of Veterinary Medicine

Department

Environmental Toxicology Program

Abstract

Phorate (O,O-diethyl S-ethylthiomethyl phosphorodithioate) is a toxic organophosphate anticholinesterase insecticide. Organophosphate insecticides can cause respiratory depression and seizures due to acetylcholinesterase inhibition. Inhibited acetylcholinesterase cannot break down the neurotransmitter, acetylcholine; thus, causing an overload of acetylcholine in synapses and neuromuscular junctions. Oxidative desulfuration, from metabolism by cytochrome P450 enzymes, converts the P=S phosphorothionate group on phorate to the P=O oxon group. Electrophilic oxon groups attack the active site on acetylcholinesterase, inducing the toxicity associated with organophosphate insecticides. Possible further bioactivation to phorate-oxon-sulfoxide and phorate-oxon-sulfone near the site of acetylcholinesterase in the brain may increase acetylcholinesterase inhibitory potency. Adult male Sprague-Dawley rat brain and liver microsomes were used to determine the proportions of the phorate metabolites formed through bioactivation. Phorate-sulfoxide was produced in much greater proportion than any other metabolite, which may contribute to the delay observed in phorate toxicity as it takes longer to produce phorate-oxon, phorate-oxon-sulfoxide, or phorate-oxon-sulfone metabolites.

URI

https://hdl.handle.net/11668/18447

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