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 - Campus Access Only

Major

Environmental Toxicology

Degree Name

Master of Science

College

College of Veterinary Medicine

Department

Department of Basic Sciences

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

Share

COinS