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Studies on the Long Term Effects of Marginal Vitamin E Deficiency on Dichloroacetate- and Trichloroacetate- Induced Phagocytic Activation in Mice

Al-Dieri, Ali
http://rave.ohiolink.edu/etdc/view?acc_num=mco1303492928

Abstract Details

2011, Master of Science in Pharmaceutical Science (MSP), University of Toledo, College of Pharmacy.
Dichloroacetate (DCA) and trichloroacetate (TCA) are major byproducts of water chlorination, and are also formed, in vivo by the metabolism of trichloroethylene (TCE), a common water contaminant. Previous studies in our lab have shown that subchronic exposure to both DCA and TCA induces phagocytic activation in the peritoneal lavage cells (PLCs) of mice. In this study, we assessed the effects of marginal vitamin E deficiency on phagocytic activation induced by DCA and TCA in B6C3F1 mice. Animals were divided in two groups, where one was kept on a regular diet supplemented with vitamin E (E-normal) and the other kept on a low vitamin E diet (E-deficient group). The two groups were divided into subgroups and were treated everyday, by gavage, with distilled water as the control, and 77mg/kg/day of DCA or TCA for a period of 13 weeks. The peritoneal lavage cells (PLCs) were collected from the animals after they were euthanized and different biomarkers of phagocytic activation, including superoxide anion (SA) and tumor necrosis factor alpha (TNF-α), as well as the activity of myeloperoxidase (MPO) were determined. Antioxidant enzyme activities, including supeoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were also assessed. Significant increases in the different biomarkers in response to DCA and TCA were reported in the E-normal and E-deficient diet groups when compared to the corresponding controls in each group. However, the increases in response to the compounds in the E-deficient groups were significantly greater than those observed in the E-normal group. Since previous studies have suggested the contribution of phagocytic activation to the protection against DCA and TCA long term effects, the increases in the biomarker of phagocytic activation in the E-deficient groups may indicate further protection provided by this mechanism against the effects induced by these compounds. SOD activity was also significantly increased in response to the compounds in either group, with more significant increases observed in the E-deficient group as compared with the E-normal group. CAT and GSH-Px activities on the other hand did not change in response to the compounds in the E-normal group but were significantly increased in the E-deficient group when compared with the corresponding controls. The increases in the antioxidant enzyme activities in response to the compounds in the E-deficient groups indicate significant SA dismutation, and conversion to water. They also suggest up-regulation of the enzyme activities in response to vitamin E deficiency, accommodating for the loss of protection by vitamin E against the compounds long term effects.
Ezdihar Hassoun, PhD (Committee Chair)
Zahoor Shah, PhD (Committee Member)
Ming-Cheh Liu, PhD (Committee Member)
53 p.
Pharmacology; Toxicology
Dichloroacetate; trichloroacetate; Vitamin E

Recommended Citations

Citations

  • Al-Dieri, A. (2011). Studies on the Long Term Effects of Marginal Vitamin E Deficiency on Dichloroacetate- and Trichloroacetate- Induced Phagocytic Activation in Mice [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1303492928

    APA Style (7th edition)

  • Al-Dieri, Ali. Studies on the Long Term Effects of Marginal Vitamin E Deficiency on Dichloroacetate- and Trichloroacetate- Induced Phagocytic Activation in Mice. 2011. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1303492928.

    MLA Style (8th edition)

  • Al-Dieri, Ali. "Studies on the Long Term Effects of Marginal Vitamin E Deficiency on Dichloroacetate- and Trichloroacetate- Induced Phagocytic Activation in Mice." Master's thesis, University of Toledo, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=mco1303492928

    Chicago Manual of Style (17th edition)

mco1303492928
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© 2011, all rights reserved.
This open access ETD is published by University of Toledo Health Science Campus and OhioLINK.