Toxicity and Physiological Actions of Carbonic Anhydrase Inhibitors to Aedes aegypti and Drosophila melanogaster

Francis, Sheena; Taylor-Wells, Jennina; Gross, Aaron D.; Bloomquist, Jeffrey R.

doi:10.3390/insects8010002

Cited by 13 publications

(10 citation statements)

References 24 publications

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“…This model was used as an equivalent system due to the limited success of using similar preparations with the mosquito CNS. These CNS preparations also proved their reliability, as in previous studies, to test the effect of drugs on dipteran nervous systems, including D. melanogaster and Musca domestica 50–52 . Dexamethasone was found to increase the rate of nerve inhibition after exposure to deltamethrin, which suggests ABC transporters are relevant to the delivery of the insecticide to the mosquito central nervous system.…”

Section: Introductionsupporting

confidence: 60%

Age- and sex-related ABC transporter expression in pyrethroid-susceptible and –resistant Aedes aegypti

Rault

Johnson

O’Neal

et al. 2019

Sci Rep

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Resistance mechanisms to synthetic insecticides often include point mutations and increased expression of genes encoding detoxification enzymes. Since pyrethroids are the main adulticides used against Aedes aegypti, which vectors pathogens such as Zika virus, understanding resistance to this insecticide class is of significant relevance. We focused on adenosine triphosphate (ATP)-binding cassette (ABC) transporters in the pyrethroid-resistant Puerto Rico (PR) strain of Ae. aegypti. We investigated the expression patterns of six ABC transporters previously characterized as differentially expressed in insecticide-challenged mosquitoes, or increased mRNA expression in pyrethroid-resistant Ae. aegypti, by comparing PR to the Rockefeller (Rock) susceptible strain. No constitutive differential expression between strains was detected, but expression differences for these genes was influenced by sex and age, suggesting that their role is independent from resistance in PR. Instead, ABC transporters may be induced after insecticide exposure. Challenging mosquitoes with deltamethrin, with or without ABC transporter modulators, showed that Rock and PR responded differently, but a contribution of ABC transporters to deltamethrin toxicity is suspected. Moreover, the effect of dexamethasone, which enhanced the inhibition of nerve firing by deltamethrin, was observed using a Drosophila central nervous system preparation, showing synergy of these two compounds through the potential inhibition of ABC transporters.

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Section: Introductionsupporting

confidence: 60%

Age- and sex-related ABC transporter expression in pyrethroid-susceptible and –resistant Aedes aegypti

Rault

Johnson

O’Neal

et al. 2019

Sci Rep

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“…Surprisingly, intrathoracic injections of flonicamid and TFNA-AM did not result in mortality >50% at doses up to 500 ng/mg. In contrast, intrathoracic injections with propoxur yielded an LD 50 value of 0.22 ng/mg, close to the value of 0.24 ng/mg reported in the literature [20]. TFNA-AM showed no lethality to mice at an oral dose of 2,000 mg/kg, and only slight hyperactivity and hyperexcitability were observed.…”

Section: A C C E P T E D Mmentioning

confidence: 72%

“…aegypti and An. gambiae (1-5 days post-eclosion) were collected and anesthetized on ice, and methods paralleled those of Francis et al [20]. Treatments Surface contact assays were performed on glass and paper.…”

Section: Mosquito Adult Toxicity Assaysmentioning

confidence: 99%

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Toxicity, mode of action, and synergist potential of flonicamid against mosquitoes

Taylor-Wells

Gross

Jiang

et al. 2018

Pesticide Biochemistry and Physiology

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The present study focused on the toxicity of the aphid anti-feedant flonicamid and its main metabolite, 4-trifluoromethylnicotinamide (TFNA-AM) to Aedes aegypti and Anopheles gambiae mosquitoes.The compounds were toxic to both species via topical application, resulting in un-coordinated locomotion and leg splaying, with a favorable An. gambiae LD 50value of 35 ng/mg for TFNA-AM, but no significant lethality to Ae. aegypti at 10 μg/female.There was mild cross resistance in the Akron-kdr (Akdr) strain of An. gambiae. Both compounds were non-toxic to intact larvae (LC 50 >300 ppm); however, headless Ae. aegypti larvae displayed spastic paralysis, with PC 50 values of 2-4 ppm, indicating that the cuticle is a significant barrier to penetration. TFNA-AM showed low mammalian toxicity, with an LD 50 of >2000 mg/kg in mice. Electrophysiological experiments showed larval Aedes muscle depolarization and Kv2 channel blocking activity that required near mM concentrations, suggesting that this potassium channel is not the main target for flonicamid nor its metabolite.However, TFNA-AM was a potent blocker of evoked body wall sensory discharge in dipteran larvae, suggesting that some component of the chordotonal organ system may be involved in its toxicity. Finally, flonicamid and TFNA-AM showed about 2-fold synergism of permethrin toxicity against An. gambiae adult females whose mechanism should become more clear once the mode of action of these compounds is better defined.

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“…NOTE: Multiple analyses can be performed on the collected data, such as changes in action potential bursts 29 , spike waveform amplitude and time course, and determining mean spike frequencies after drug treatment 26,30,31,32 . The most common is determining the influence a drug has to the mean spike frequencies over a specified period of time, which is described below.…”

Section: Extracellular Recording Of Drosophila Cnsmentioning

confidence: 99%

Electrophysiological Recording of The Central Nervous System Activity of Third-Instar <em> Drosophila Melanogaster </em>

Swale

Gross

Coquerel

et al. 2018

JoVE

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The majority of the currently available insecticides target the nervous system and genetic mutations of invertebrate neural proteins oftentimes yield deleterious consequences, yet the current methods for recording nervous system activity of an individual animal is costly and laborious. This suction electrode preparation of the third-instar larval central nervous system of Drosophila melanogaster, is a tractable system for testing the physiological effects of neuroactive agents, determining the physiological role of various neural pathways to CNS activity, as well as the influence of genetic mutations to neural function. This ex vivo preparation requires only moderate dissecting skill and electrophysiological expertise to generate reproducible recordings of insect neuronal activity. A wide variety of chemical modulators, including peptides, can then be applied directly to the nervous system in solution with the physiological saline to measure the influence on the CNS activity. Further, genetic technologies, such as the GAL4/UAS system, can be applied independently or in tandem with pharmacological agents to determine the role of specific ion channels, transporters, or receptors to arthropod CNS function. In this context, the assays described herein are of significant interest to insecticide toxicologists, insect physiologists, and developmental biologists for which D. melanogaster is an established model organism. The goal of this protocol is to describe an electrophysiological method to enable the measurement of electrogenesis of the central nervous system in the model insect, Drosophila melanogaster, which is useful for testing a diversity of scientific hypotheses. | 141 | e58375 | Page 4 of 9 4. Perform statistical analysis (e.g., unpaired t-test) to determine significance between time points, concentrations, or drug treatments. NOTE: There are two primary methods for generating and analyzing concentration-response curves. The first method is one concentration per individual preparation. Here, the spike rate of the single concentration is normalized to baseline spike rate for each preparation. The benefits are reduced run down of the preparation due to shortened recording time, while the pitfalls are increased dissection time because this method will consist of 5-7 individual CNS preparations per concentration, and larger error bars on the averaged data set. The second method is multiple concentrations per individual preparation. Here, the spike rate for each of the 3-5 concentrations are normalized to the same baseline spike rate. The benefits are less dissection time and less variability between replicates for drug concentrations, while the pitfalls are the requirement of a fast-acting drug and unknown impact of previous drug concentration treatments on subsequent chemical treatments. 30

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Toxicity and Physiological Actions of Carbonic Anhydrase Inhibitors to Aedes aegypti and Drosophila melanogaster

Cited by 13 publications

References 24 publications

Age- and sex-related ABC transporter expression in pyrethroid-susceptible and –resistant Aedes aegypti

Age- and sex-related ABC transporter expression in pyrethroid-susceptible and –resistant Aedes aegypti

Toxicity, mode of action, and synergist potential of flonicamid against mosquitoes

Electrophysiological Recording of The Central Nervous System Activity of Third-Instar <em> Drosophila Melanogaster </em>

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