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Apoptosis and Cardiotoxicity Induced by Acute Methamphetamine Exposure in Larval Zebrafish (Danio rerio)

Sree Kumar, Hemaa
http://rave.ohiolink.edu/etdc/view?acc_num=mco1607106063115885

Abstract Details

2020, Master of Science (MS), University of Toledo, Pharmaceutical Sciences (Pharmacology/Toxicology).
According to the 2020 World Drug Report, amphetamine type stimulant (ATS) is the third most used illicit drug with 27 million users globally. Methamphetamine (MA) is a potent central nervous system (CNS) stimulant with a high abuse potential and addiction. MA use has become an increasing concern worldwide especially due to the adverse effects it possesses. MA is also known as the poor man’s cocaine since it is more easily accessible “illegally” and inexpensive compared to cocaine. The euphoric feeling from MA also lasts longer than cocaine due to its long half-life (10-12h) and lipophilicity that allows MA to better penetrate the blood brain barrier (BBB) easily. The primary aim of this study was to study the acute toxic effects of MA that may contribute to acute lethality as well as to long-term adverse effects associated with MA use. The hypothesis of this study is that death in 5-dpf larval zebrafish is due to apoptosis in the cardiovascular system and/or in the brain secondary to acute MA exposure. MA works by causing an increase in the levels of dopamine (DA), norepinephrine (NE), serotonin (5-HT) and preventing the re-uptake of these neurotransmitters (NT) by blocking monoamine transporters, which then increases the levels of the NT in the synaptic cleft. An increase in DA, NE, 5-HT causes users to experience intense euphoric feelings, increased heart rate (tachycardia), hyperthermia, increased energy, hypertension and decrease in appetite. Some of the chronic abuse of MA leads to neurotoxicity, agitation, aggression, anxiety, psychosis, renal and liver failure, seizure, and cardiac arrhythmias, heart attacks. In this study, we used 5-day old larval zebrafish and exposed them to three different concentrations (0mM, 5mM and 15mM) of MA for 5-hr to assess change in heart rate and other lethality parameters such as lack of heartbeat, opaque appearance and notochord bend (lordosis). Subjects were then processed for cleaved caspase-3 immunofluorescence assay and Western Blotting. Change in heart rate for subjects in 5mM group was not significant. Conversely, significant decline in heart rate was observed in the 15mM cohort as the duration of exposure increases starting at 1h time point. Cell death which could be due to the apoptosis involving caspase-3 involving otolith, hindbrain, notochord and caudal tail was observed via immunofluorescence staining. Apoptosis was found to be more significant in the 15mM cohort. There seem to be an involvement of the cardiovascular (CV) system secondary to acute MA exposure, however, the mechanisms involved in cell death is unclear. Additional studies and different techniques could be utilized in future studies to elucidate a mechanism that may be contributing to cell death following acute exposure to MA.
Frederick Williams (Advisor)
Scott Hall (Committee Member)
Zahoor Shah (Committee Member)
62 p.
Pharmacology; Toxicology
apoptosis, zebrafish, methamphetamine, acute, cardiotoxicity, lethality

Recommended Citations

Citations

  • Sree Kumar, H. (2020). Apoptosis and Cardiotoxicity Induced by Acute Methamphetamine Exposure in Larval Zebrafish (Danio rerio) [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1607106063115885

    APA Style (7th edition)

  • Sree Kumar, Hemaa. Apoptosis and Cardiotoxicity Induced by Acute Methamphetamine Exposure in Larval Zebrafish (Danio rerio) . 2020. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1607106063115885.

    MLA Style (8th edition)

  • Sree Kumar, Hemaa. "Apoptosis and Cardiotoxicity Induced by Acute Methamphetamine Exposure in Larval Zebrafish (Danio rerio) ." Master's thesis, University of Toledo, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=mco1607106063115885

    Chicago Manual of Style (17th edition)

mco1607106063115885
222
© 2020, all rights reserved.
This open access ETD is published by University of Toledo Health Science Campus and OhioLINK.