title: Polychlorinated biphenyls as oxidative stress inducers in liver of subacutely exposed rats: implication for dose-dependence toxicity and benchmark dose concept.
abstract: Hepatotoxicity is one of the well-documented adverse health effects of polychlorinated biphenyls (PCBs)-persistent organic pollutants widely present in the environment. Although previous studies suggest possible role of oxidative stress, the precise mechanisms of PCB-induced ROS production in liver still remain to be fully assessed. The aim of this study was to evaluate the effects of different doses of PCBs on the parameters of oxidative stress and to investigate whether these effects are dose dependent. Furthermore, a comparison between calculated benchmark doses (BMD) and estimated NOAEL values for investigated parameters, was made. Six groups of male albino Wistar rats (7 animals per group) were receiving Aroclor 1254 dissolved in corn oil in the doses of 0.5, 1, 2, 4, 8, 16 mg PCBs/kg b.w./day by oral gavage during 28 days while control animals were receiving corn oil only. The following parameters of oxidative stress were analyzed in liver homogenates: superoxide dismutase activity, glutathione, malondialdehyde (MDA) and total protein thiol levels. Hepatic enzymes AST, ALT, ALP and protein albumin were also determined in serum as clinical parameters of liver function. Collected data on the investigated parameters were analyzed by the BMD method. The results of this study demonstrate that subacute exposure to PCBs causes induction of oxidative stress in liver with dose-dependent changes of the investigated parameters, although more pronounced adverse effects were observed on enzymatic than on non-enzymatic components of antioxidant protection. The obtained values for BMD and NOAEL support the use of BMD concept in the prediction of health risks associated with PCBs exposure. Furthermore, our results implicate possible use of MDA in PCBs risk assessment, since MDA was the most sensitive investigated parameter with calculated low critical effect dose of 0.07 mg/kg b.w.
authors.affiliation: Department of Toxicology "Akademik Danilo Soldatović", University of Belgrade-Faculty of Pharmacy, Belgrade, Serbia. Electronic address: aleksandra@pharmacy.bg.ac.rs.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Buha
authors.affiliation: Department of Toxicology "Akademik Danilo Soldatović", University of Belgrade-Faculty of Pharmacy, Belgrade, Serbia.
authors.forename: Biljana
authors.initials: B
authors.lastname: Antonijević
authors.affiliation: Chemicals Department, Ministry of Agriculture and Environmental Protection of Republic of Serbia, Belgrade, Serbia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Milovanović
authors.affiliation: Institute of Meat Hygiene and Technology, Belgrade, Serbia.
authors.forename: Saša
authors.initials: S
authors.lastname: Janković
authors.affiliation: Department of Toxicology "Akademik Danilo Soldatović", University of Belgrade-Faculty of Pharmacy, Belgrade, Serbia.
authors.forename: Zorica
authors.initials: Z
authors.lastname: Bulat
authors.affiliation: Department of Toxicology "Akademik Danilo Soldatović", University of Belgrade-Faculty of Pharmacy, Belgrade, Serbia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Matović
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D018384:Oxidative Stress / Q000187:drug effects*; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D011078:Polychlorinated Biphenyls
keywords: Dose-dependence; Hepatotoxicity; Oxidative stress; Polychlorinated biphenyls; Rats