Master of Science (MS), University of Toledo, 2015, Pharmaceutical Sciences (Pharmacology/Toxicology)
The process of water chlorination results in production of different disinfection byproducts (DBPs), including dichloroacetate (DCA) and trichloroacetate (TCA). The compounds have been found to be hepatotoxic and hepatocarcinogenic in rodents. Previous studies have indicated the roles of oxidative stress (OS) and phagocytic activations in the induction of these effects in B6C3F1 mice. Also, previous studies have reported effects of DCA and TCA mixtures that ranged from additive to greater than additive on the induction of hepatic OS and additive to less than additive on the induction of phagocytic activation in mice. In this study, frozen peritoneal lavage cells collected from mice treated for those previous studies were used. In those studies, groups of mice were administered 7.5, 15, 30 mg/kg/day of DCA, 12.5, 25, 50 mg/kg/day of TCA, and 3 different mixtures of the compounds (Mix I, Mix II and Mix III) post orally for 13 weeks. The DCA: TCA ratios in Mix I, Mix II, Mix III corresponded to 7.5:12.5, 15:25, 30:50 mg/kg/day, respectively. Mice were then sacrificed and the peritoneal lavage cells (PLCs) were isolated and kept frozen at -80 C. Cells were assayed for the activities of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), as well as for the amount of glutathione (GSH). DCA, TCA and mixtures administration resulted in dose-dependent increases in SOD activity. Also, DCA, TCA, and mixture I treatments resulted in no change in CAT or GSH-Px activities while Mix II and Mix III resulted in significant increases in those enzyme activities. While 50 mg/kg/day TCA, and Mix I and Mix. II resulted in significant increases in total GSH levels; the rest of the other treatments did not result in significant changes in the levels of that biomarker. Failure of phagocytic activation has been previously suggested to contribute to increases in the hepatotoxic/ hepatocarcinogenic effects of DCA and TCA, and mixtur (open full item for complete abstract)
Committee: Ezdihar Hassoun (Committee Chair); Ming-Cheh Liu (Committee Member); Zahoor Shah (Committee Member)
Subjects: Pharmacology; Pharmacy Sciences; Toxicology