Toxicological Analysis of Tacrines and Verapamil on the Yellow Fever Mosquito, Aedes aegypti

Mosquitoes affect human health worldwide as a result of their ability to vector multiple diseases. Mosquitocide resistance is a serious public health challenge that warrants the development of improved chemical control strategies for mosquitoes. Previous studies demonstrate the mosquito blood-brain barrier (BBB) to interfere with the target-site delivery and action of anticholinesterase chemistries. The ATP-binding cassette (ABC) transporters are efflux proteins that assist in maintaining the BBB interface and serve as a first line of defense to mosquitocide exposures. To date, there are three subfamilies (ABC -B, -C, -G) of ABC transporters; however, knowledge of these chemistries interacting with mosquito ABC transporter(s) is limited. Here, I report that tacrine and bis(7)-tacrine are relative non-toxic anticholinesterases at solubility limits; however, the addition of verapamil enhances toxicity of both tacrine and bis(7)-tacrine to mosquitoes. Verapamil significantly increases the mortality of mosquitoes exposed to tacrine and bis(7)-tacrine compared to the tacrine- and bis(7)- tacrine-only treatments. Tacrine and bis(7)-tacrine reduce acetylcholinesterase activity in mosquito head preparations compared to the untreated mosquitoes; however, the addition of verapamil significantly increases the anticholinesterase activity of tacrine and bis(7)-tacrine compared to the tacrine-and bis(7)-tacrine-only treatments. Tacrine and bis(7)-tacrine increase ATPase activity in Aedes aegypti at lower concentrations compared to that of verapamil (Fig. 3). The differential increase in ATPase activity suggests that tacrine and bis(7)-tacrine are more suitable substrates for ABC transporter(s) compared to verapamil and, thus, provides putative evidence that ABC transporter(s) is a pharmacological obstacle to the delivery of these anticholinesterases to their intended target site.

Name thesis:degree_name

Master of Science in Life Sciences

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

Entomology

Department dc:contributor.department

Entomology

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2016

Author dc:creator

• Pham, Ngoc Nhu

Chair dc:contributor.committeechair

• Anderson, Troy D.

Committee members dc:contributor.committeemember

• Paulson, Sally L.
• Brewster, Carlyle C.
• Carlier, Paul R.
• Li, Jianyong

• mosquito
• tacrines
• verapamil
• acetylcholinesterase ATPase activity
• ABC transporter

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Dc Identifier Other

vt_gsexam:7264

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/71699