title: Ameliorative effects of docosahexaenoic acid on the toxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in cultured rat hepatocytes.
abstract: The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant toxicant that mediates carcinogenic effects associated with oxidative DNA damage. Docosahexaenoic acid (DHA) with antioxidant functions has many biochemical, cellular, and physiological functions for cells. The present study assessed, for the first time, the ameliorative effect of DHA in alleviating the toxicity of TCDD on primary cultured rat hepatocytes (HEPs). In vitro, isolated HEPs were incubated with TCDD (5 and 10 μM) in the presence and absence of DHA (5, 10, and 20 μM) for 48 h. The cell viability was detected by 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) release. DNA damage was analyzed by liver micronucleus assay and 8-oxo-2-deoxyguanosine (8-OH-dG) level. In addition, total antioxidant capacity (TAC) and total oxidative stress (TOS) were assessed to determine the oxidative injury in HEPs. The results of MTT and LDH assays showed that TCDD decreased cell viability but not DHA. On the basis of increasing treatment concentrations, the dioxin caused significant increases of micronucleated HEPs and 8-OH-dG as compared to control culture. TCDD also led to significant increases in TOS content. On the contrary, in cultures treated with DHA, the level of TAC was significantly increased during treatment in a concentration-dependent fashion. DHA showed therapeutic potential against TCDD-mediated cell viability and DNA damages. As conclusion, this study provides the first evidence that DHA has protective effects against TCDD toxicity on primary cultured rat hepatocytes.
authors.affiliation: Department of Molecular Biology and Genetics, Faculty of Science, Erzurum Technical University, Erzurum, Turkey.
authors.forename: Hasan
authors.initials: H
authors.lastname: Turkez
authors.affiliation: Department of Biology, Faculty of Science, Atatürk University, Erzurum, Turkey geyikogluff@yahoo.com.
authors.forename: Fatime
authors.initials: F
authors.lastname: Geyikoglu
authors.affiliation: Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt.
authors.forename: Mokhtar I
authors.initials: MI
authors.lastname: Yousef
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D015162:Micronucleus Tests; D018384:Oxidative Stress / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D000072317:Polychlorinated Dibenzodioxins; D020011:Protective Agents; D004281:Docosahexaenoic Acids; D000080242:8-Hydroxy-2'-Deoxyguanosine; D007770:L-Lactate Dehydrogenase; D003849:Deoxyguanosine
keywords: 2; 3; 7; 8-oxo-2-deoxyguanosine; 8-tetrachlorodibenzo-p-dioxin; Docosahexaenoic acid; antioxidant capacity; cell viability; liver; micronucleus assay; oxidative stress; rat