2021
Vondráček, Jan; Machala, Miroslav
The Role of Metabolism in Toxicity of Polycyclic Aromatic Hydrocarbons and their Non-genotoxic Modes of Action. Journal Article
In: Current drug metabolism, vol. 22, no. 8, pp. 584–595, 2021, ISSN: 1875-5453 1389-2002, (Place: Netherlands).
Abstract | Links | BibTeX | Tags: Activation, AhR, Animals, Benzo[a]pyrene, Cell Proliferation, Cell Survival, cell-to-cell communication, DNA Damage, Environmental Pollutants/*pharmacokinetics/*toxicity, Humans, Metabolic, Mutagens/*pharmacokinetics/*toxicity, oxidative stress, PAH metabolism., Polycyclic Aromatic Hydrocarbons/*pharmacokinetics/*toxicity
@article{vondracek_role_2021,
title = {The Role of Metabolism in Toxicity of Polycyclic Aromatic Hydrocarbons and their Non-genotoxic Modes of Action.},
author = {Jan Vondráček and Miroslav Machala},
doi = {10.2174/1389200221999201125205725},
issn = {1875-5453 1389-2002},
year = {2021},
date = {2021-01-01},
journal = {Current drug metabolism},
volume = {22},
number = {8},
pages = {584–595},
abstract = {Polycyclic aromatic hydrocarbons (PAHs) represent a class of widely distributed environmental pollutants that have been primarily studied as genotoxic compounds. Their mutagenicity/genotoxicity largely depends on their oxidative metabolism leading to the production of dihydrodiol epoxide metabolites, as well as additional metabolites contributing to oxidative DNA damage, such as PAH quinones. However, both parental PAHs and their metabolites, including PAH quinones or hydroxylated PAHs, have been shown to produce various types of non-genotoxic effects. These include e.g., activation of the aryl hydrocarbon receptor and/or additional nuclear receptors, activation of membrane receptors, including tyrosine kinases and G-protein coupled receptors, or activation of intracellular signaling pathways, such as mitogen-activated protein kinases, Akt kinase and Ca(2+)-dependent signaling. These pathways may, together with the cellular DNA damage responses, modulate cell proliferation, cell survival or cell-to-cell communication, thus contributing to the known carcinogenic effects of PAHs. In the present review, we summarize some of the known non-genotoxic effects of PAHs, focusing primarily on those that have also been shown to be modulated by PAH metabolites. Despite the limitations of the available data, it seems evident that more attention should be paid to the discrimination between the potential non-genotoxic effects of parental PAHs and those of their metabolites. This may provide further insight into the mechanisms of toxicity of this large and diverse group of environmental pollutants.},
note = {Place: Netherlands},
keywords = {Activation, AhR, Animals, Benzo[a]pyrene, Cell Proliferation, Cell Survival, cell-to-cell communication, DNA Damage, Environmental Pollutants/*pharmacokinetics/*toxicity, Humans, Metabolic, Mutagens/*pharmacokinetics/*toxicity, oxidative stress, PAH metabolism., Polycyclic Aromatic Hydrocarbons/*pharmacokinetics/*toxicity},
pubstate = {published},
tppubtype = {article}
}
Polycyclic aromatic hydrocarbons (PAHs) represent a class of widely distributed environmental pollutants that have been primarily studied as genotoxic compounds. Their mutagenicity/genotoxicity largely depends on their oxidative metabolism leading to the production of dihydrodiol epoxide metabolites, as well as additional metabolites contributing to oxidative DNA damage, such as PAH quinones. However, both parental PAHs and their metabolites, including PAH quinones or hydroxylated PAHs, have been shown to produce various types of non-genotoxic effects. These include e.g., activation of the aryl hydrocarbon receptor and/or additional nuclear receptors, activation of membrane receptors, including tyrosine kinases and G-protein coupled receptors, or activation of intracellular signaling pathways, such as mitogen-activated protein kinases, Akt kinase and Ca(2+)-dependent signaling. These pathways may, together with the cellular DNA damage responses, modulate cell proliferation, cell survival or cell-to-cell communication, thus contributing to the known carcinogenic effects of PAHs. In the present review, we summarize some of the known non-genotoxic effects of PAHs, focusing primarily on those that have also been shown to be modulated by PAH metabolites. Despite the limitations of the available data, it seems evident that more attention should be paid to the discrimination between the potential non-genotoxic effects of parental PAHs and those of their metabolites. This may provide further insight into the mechanisms of toxicity of this large and diverse group of environmental pollutants.
2002
Kubala, Lukás; Cíz, Milan; Vondrácek, Jan; Cerný, Jan; Nemec, Petr; Studeník, Pavel; Cizová, Hana; Lojek, Antonín
In: The Journal of thoracic and cardiovascular surgery, vol. 124, no. 6, pp. 1122–1129, 2002, ISSN: 0022-5223, (Place: United States).
Abstract | Links | BibTeX | Tags: *Cardiac Surgical Procedures, *Heart Transplantation, Cardiopulmonary Bypass, Cytokines/*metabolism, Female, Humans, Interleukin-10/metabolism, Interleukin-6/metabolism, Interleukin-8/metabolism, Male, Middle Aged, Neutrophils/*metabolism, oxidative stress, Phagocytosis, Time Factors
@article{kubala_perioperative_2002,
title = {Perioperative and postoperative course of cytokines and the metabolic activity of neutrophils in human cardiac operations and heart transplantation.},
author = {Lukás Kubala and Milan Cíz and Jan Vondrácek and Jan Cerný and Petr Nemec and Pavel Studeník and Hana Cizová and Antonín Lojek},
doi = {10.1067/mtc.2002.125814},
issn = {0022-5223},
year = {2002},
date = {2002-12-01},
journal = {The Journal of thoracic and cardiovascular surgery},
volume = {124},
number = {6},
pages = {1122–1129},
abstract = {OBJECTIVES: The purpose of this study was to compare systemic inflammatory responses after heart transplantation and nontransplant cardiac operations, both involving cardiopulmonary bypass with a focus on the role of polymorphonuclear leukocytes. METHODS: Lipid peroxidation, blood phagocyte radical production, and interleukin 6, 8, and 10 plasma concentrations during surgical intervention and on the first and seventh postoperative days were evaluated in patients undergoing heart transplantation (n = 24) and in patients not undergoing transplantation (n = 30). RESULTS: Levels of interleukin 6, 8, and 10 increased in both groups of patients during early reperfusion. They normalized within the first postoperative day in the transplant group, whereas the nontransplant group's interleukin 6 and 8 levels remained increased on the seventh day after the operation. Interleukin 10 plasma levels were higher in the heart transplant group during reperfusion. Lipid peroxidation was increased after the operation in both groups of patients. Phagocyte activity was enhanced at reperfusion and at all other sampling times only in the nontransplant group. On the other hand, phagocyte activity oscillated around the preoperative level during heart transplantation, or it was even decreased. CONCLUSION: Both cardiac operations involving heart transplantation and those without transplantation are associated with increased oxidative stress and an enhanced production of proinflammatory and anti-inflammatory cytokines. Differences in interleukin 10 production and phagocyte activity could be caused mainly by the immunosuppressive therapy in heart transplant operations.},
note = {Place: United States},
keywords = {*Cardiac Surgical Procedures, *Heart Transplantation, Cardiopulmonary Bypass, Cytokines/*metabolism, Female, Humans, Interleukin-10/metabolism, Interleukin-6/metabolism, Interleukin-8/metabolism, Male, Middle Aged, Neutrophils/*metabolism, oxidative stress, Phagocytosis, Time Factors},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVES: The purpose of this study was to compare systemic inflammatory responses after heart transplantation and nontransplant cardiac operations, both involving cardiopulmonary bypass with a focus on the role of polymorphonuclear leukocytes. METHODS: Lipid peroxidation, blood phagocyte radical production, and interleukin 6, 8, and 10 plasma concentrations during surgical intervention and on the first and seventh postoperative days were evaluated in patients undergoing heart transplantation (n = 24) and in patients not undergoing transplantation (n = 30). RESULTS: Levels of interleukin 6, 8, and 10 increased in both groups of patients during early reperfusion. They normalized within the first postoperative day in the transplant group, whereas the nontransplant group's interleukin 6 and 8 levels remained increased on the seventh day after the operation. Interleukin 10 plasma levels were higher in the heart transplant group during reperfusion. Lipid peroxidation was increased after the operation in both groups of patients. Phagocyte activity was enhanced at reperfusion and at all other sampling times only in the nontransplant group. On the other hand, phagocyte activity oscillated around the preoperative level during heart transplantation, or it was even decreased. CONCLUSION: Both cardiac operations involving heart transplantation and those without transplantation are associated with increased oxidative stress and an enhanced production of proinflammatory and anti-inflammatory cytokines. Differences in interleukin 10 production and phagocyte activity could be caused mainly by the immunosuppressive therapy in heart transplant operations.