Dichloroacetate- and trichloroacetate-induced phagocytic activation and production of oxidative stress in the hepatic tissues of mice after acute exposure.
Dichoroacetate (DCA) and trichloroacetate (TCA) are by-products formed during chlorination of the drinking water and were found to be hepatotoxic and hepatocarcinogenic in rodents. In this study, the abilities of the compounds to induce oxidative stress and phagocytic activation have been studied in B6C3F1 mice. Groups of mice were administered 300 mg/kg of either DCA or TCA, p.o, and were sacrificed after 6 or 12 h. Peritoneal lavage cells (PLCs) were isolated and assayed for superoxide anion (SA) production, and hepatic tissues were assayed for the production of SA, lipid peroxidation (LP), and DNA-single strand breaks (SSBs). TCA resulted in significant production of SA in the PLCs, and in the production of SA, LP, and DNA-SSBs in the hepatic tissues, 12 h after dosing, as compared with the control. DCA administration, on the other hand, resulted in significant increases in the productions of LP and DNA-SSBs in the hepatic tissues at both time points, and in SA production in PLCs and hepatic tissues, 6 h after dosing. However, DCA-induced increases in SA production in PLC and hepatic tissues declined at the 12-h time point, reaching control level in the hepatic tissues. These results may implicate the contribution of phagocytic activation to the induction of oxidative stress in the hepatic tissues and also the role of SA production in the induction of LP and/or DNA damage in those tissues, in response to the compounds. The results also suggest studying the involvement of these mechanisms in the long-term hepatotoxicity/hepatocarcinogencity of the compounds.
Hassoun
Ezdihar A
EA
College of Pharmacy, The University of Toledo, Toledo, OH 43606, USA. ehassou@utnet.utoledo.edu
Dey
Soumyadeep
S
D000818:Animals; D045304:Cytochromes c / Q000378:metabolism; D053904:DNA Breaks, Single-Stranded / Q000187:drug effects; D003999:Dichloroacetic Acid / Q000008:administration & dosage / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D051379:Mice; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010533:Peritoneal Lavage; D010587:Phagocytosis / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014238:Trichloroacetic Acid / Q000008:administration & dosage / Q000633:toxicity*
D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D014238:Trichloroacetic Acid; D045304:Cytochromes c; D003999:Dichloroacetic Acid