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Thesis for Mohammed Abdulkareem.pdf (852.73 KB)

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The Interaction Between Dichloroacetate, Trichloroacetate and Acetaminophen: Effects on Oxidative Stress Induction in AML 12 Cells

Abdulkareem, Mohammed Hasan
http://rave.ohiolink.edu/etdc/view?acc_num=mco1469703005

Abstract Details

2016, Master of Science in Pharmaceutical Science (MSP), University of Toledo, Pharmaceutical Sciences (Pharmacology/Toxicology).
Water chlorination process results in the formation of different haloacetate by- products, such as dichloroacetate (DCA) and trichloroacetate (TCA). Those compounds were previously found to be hepatotoxic and hepatocarcinogenic in rodents, and oxidative stress (OS) plays a role in that. Acetaminophen is a widely used analgesic and antipyretic, and doses above the therapeutic level are known to result in liver failure and hepatic damage. Therefore, we proposed a possible increase in induction of liver cells damage after exposure to mixtures of DCA, TCA and acetaminophen. To test this hypothesis, we performed in vitro studies using alpha mouse liver 12 (AML 12) cells as a model to screen the effects of mixtures of the compounds. Individual compounds and different mixtures of the compounds were incubated with the cells for 48 hours, and cellular viability and various biomarkers of OS production, including superoxide anions (SA), advanced oxidation protein products (AOPP), nitric oxide (NO) and lipid peroxidation were determined. DCA and TCA were tested at concentrations of 770 and 500 ppm, respectively, since they were previously shown to result in 25% cell death. A concentration of 755.8 ppm of acetaminophen was found in this study to produce 25 % decrease in cellular viability, and was therefore used in the tested mixtures. Three binary mixtures, as well as a mixture of the three compounds were tested. All of the binary mixtures and the 3-compound mixture resulted in additive effects on the reduction in cellular viability. However, the net effects of the binary mixtures on the production of various biomarkers of OS was variable and ranged from less than additive to additive effect, but those of the 3-compound mixture on those biomarkers were all significant increases that ranged from additive to greater than additive effects. It is concluded that the compounds induce significantly greater effects on AML 12 cells when they exist in the form of a 3-compound mixture and a focus should therefore be given in the future to studying different mixture compositions containing the three compounds, both in vitro and in vivo.
Ezdihar Hassoun (Committee Chair)
Ming Liu (Committee Member)
Jerry Nesamony (Committee Member)
39 p.
Pharmaceuticals; Pharmacology; Pharmacy Sciences; Toxicology

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Citations

  • Abdulkareem, M. H. (2016). The Interaction Between Dichloroacetate, Trichloroacetate and Acetaminophen: Effects on Oxidative Stress Induction in AML 12 Cells [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1469703005

    APA Style (7th edition)

  • Abdulkareem, Mohammed. The Interaction Between Dichloroacetate, Trichloroacetate and Acetaminophen: Effects on Oxidative Stress Induction in AML 12 Cells. 2016. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1469703005.

    MLA Style (8th edition)

  • Abdulkareem, Mohammed. "The Interaction Between Dichloroacetate, Trichloroacetate and Acetaminophen: Effects on Oxidative Stress Induction in AML 12 Cells." Master's thesis, University of Toledo, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=mco1469703005

    Chicago Manual of Style (17th edition)

mco1469703005
418
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This open access ETD is published by University of Toledo Health Science Campus and OhioLINK.