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Polychlorinated biphenyls as oxidative stress inducers in liver of subacutely exposed rats: Implication for dose-dependence toxicity and benchmark dose concept
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 activit...y, 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.
TY - JOUR
AU - Buha, Aleksandra
AU - Antonijević, Biljana
AU - Milovanović, Vesna
AU - Janković, Saša
AU - Bulat, Zorica
AU - Matović, Vesna
PY - 2015
UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2456
AB - 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.
PB - Academic Press Inc Elsevier Science, San Diego
T2 - Environmental Research
T1 - Polychlorinated biphenyls as oxidative stress inducers in liver of subacutely exposed rats: Implication for dose-dependence toxicity and benchmark dose concept
VL - 136
SP - 309
EP - 317
DO - 10.1016/j.envres.2014.11.005
ER -
@article{
author = "Buha, Aleksandra and Antonijević, Biljana and Milovanović, Vesna and Janković, Saša and Bulat, Zorica and Matović, Vesna",
year = "2015",
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.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Environmental Research",
title = "Polychlorinated biphenyls as oxidative stress inducers in liver of subacutely exposed rats: Implication for dose-dependence toxicity and benchmark dose concept",
volume = "136",
pages = "309-317",
doi = "10.1016/j.envres.2014.11.005"
}
Buha, A., Antonijević, B., Milovanović, V., Janković, S., Bulat, Z.,& Matović, V.. (2015). Polychlorinated biphenyls as oxidative stress inducers in liver of subacutely exposed rats: Implication for dose-dependence toxicity and benchmark dose concept. in Environmental Research
Academic Press Inc Elsevier Science, San Diego., 136, 309-317.
https://doi.org/10.1016/j.envres.2014.11.005
Buha A, Antonijević B, Milovanović V, Janković S, Bulat Z, Matović V. Polychlorinated biphenyls as oxidative stress inducers in liver of subacutely exposed rats: Implication for dose-dependence toxicity and benchmark dose concept. in Environmental Research. 2015;136:309-317.
doi:10.1016/j.envres.2014.11.005 .
Buha, Aleksandra, Antonijević, Biljana, Milovanović, Vesna, Janković, Saša, Bulat, Zorica, Matović, Vesna, "Polychlorinated biphenyls as oxidative stress inducers in liver of subacutely exposed rats: Implication for dose-dependence toxicity and benchmark dose concept" in Environmental Research, 136 (2015):309-317,
https://doi.org/10.1016/j.envres.2014.11.005 . .
