Pub Date : 2003-09-01DOI: 10.1080/08865140390450359
José María Monserrat, L. Geracitano, A. Bianchini
The possibility of detecting aquatic pollution problems to take corrective decisions is intimately related to the organization levels of the living matter. Measurements at the biochemical or physiological levels detect more quickly and specifically the presence of several toxic compounds, allowing its utilization in a prospective way, until that deleterious effect reaches higher organization levels. The detection of environmental “hot spots” needs general nonspecific biomarkers if no previous information about the presence of specific pollutants exist. Since several xenobiotics can modify directly or indirectly the balance between pro-oxidant and antioxidant concentration, the determination of oxidative stress (DNA damage, protein oxidation, lipid peroxidation) in aquatic species is commonly used as a nonspecific biomarker. On the other hand, acetylcholinesterase activity or determination of metallothionein concentration (or expression) represents specific biomarkers that indicate the presence of anticholinesterasic compounds (organophosphorus pesticides or neurotoxins, for instance) and metals, respectively. The fact that animal populations inhabiting polluted areas can express responses qualitatively and quantitatively different from those of reference areas has lead to the “pollution induced community tolerance” approach that seems to be a valuable tool to compare toxicological responses of different aquatic populations.
{"title":"Current and Future Perspectives Using Biomarkers to Assess Pollution in Aquatic Ecosystems","authors":"José María Monserrat, L. Geracitano, A. Bianchini","doi":"10.1080/08865140390450359","DOIUrl":"https://doi.org/10.1080/08865140390450359","url":null,"abstract":"The possibility of detecting aquatic pollution problems to take corrective decisions is intimately related to the organization levels of the living matter. Measurements at the biochemical or physiological levels detect more quickly and specifically the presence of several toxic compounds, allowing its utilization in a prospective way, until that deleterious effect reaches higher organization levels. The detection of environmental “hot spots” needs general nonspecific biomarkers if no previous information about the presence of specific pollutants exist. Since several xenobiotics can modify directly or indirectly the balance between pro-oxidant and antioxidant concentration, the determination of oxidative stress (DNA damage, protein oxidation, lipid peroxidation) in aquatic species is commonly used as a nonspecific biomarker. On the other hand, acetylcholinesterase activity or determination of metallothionein concentration (or expression) represents specific biomarkers that indicate the presence of anticholinesterasic compounds (organophosphorus pesticides or neurotoxins, for instance) and metals, respectively. The fact that animal populations inhabiting polluted areas can express responses qualitatively and quantitatively different from those of reference areas has lead to the “pollution induced community tolerance” approach that seems to be a valuable tool to compare toxicological responses of different aquatic populations.","PeriodicalId":402874,"journal":{"name":"Comments on Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122356123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2003-09-01DOI: 10.1080/08865140390450331
José María Monserrat
This special issue is devoted to analyzing the state-of-the art of biomarkers of exposure and effect in aquatic species. The increasing human population is imposing several problems on our planet. Biochemical and physiological parameters can be employed to determine if an organism has been exposed to one or more pollutants or if deleterious effects are evident after exposure to complex mixtures of pollutants. The quickness by which these parameters can be measured is an advantage when corrective decisions have to made taking into account quantitative and reliable information. Also, as discussed in this issue, measurements at the biochemical or physiological levels detect more quickly and specifically the presence of several toxic compounds, allowing this information to be used in a prospective way, avoiding the appearance of deleterious effects at higher organization levels such as communities. All the contributors to this issue are researchers with experience in the use of biomarkers to detect and evaluate pollution problems. Several are from Brazil, a country with more than 8,000km of coast, a geographical characteristic that imposes the need to evaluate the quality of aquatic resources. The study and development of pollution biomarkers can be related to several different areas. Because the growing of the human population has lead to the search for alternative ways to produce food, aquaculture has become a broadly accepted alternative. However, food quality generated by aquaculture practices is directly
{"title":"Overview: Biomarkers of Pollution in Aquatic Animals","authors":"José María Monserrat","doi":"10.1080/08865140390450331","DOIUrl":"https://doi.org/10.1080/08865140390450331","url":null,"abstract":"This special issue is devoted to analyzing the state-of-the art of biomarkers of exposure and effect in aquatic species. The increasing human population is imposing several problems on our planet. Biochemical and physiological parameters can be employed to determine if an organism has been exposed to one or more pollutants or if deleterious effects are evident after exposure to complex mixtures of pollutants. The quickness by which these parameters can be measured is an advantage when corrective decisions have to made taking into account quantitative and reliable information. Also, as discussed in this issue, measurements at the biochemical or physiological levels detect more quickly and specifically the presence of several toxic compounds, allowing this information to be used in a prospective way, avoiding the appearance of deleterious effects at higher organization levels such as communities. All the contributors to this issue are researchers with experience in the use of biomarkers to detect and evaluate pollution problems. Several are from Brazil, a country with more than 8,000km of coast, a geographical characteristic that imposes the need to evaluate the quality of aquatic resources. The study and development of pollution biomarkers can be related to several different areas. Because the growing of the human population has lead to the search for alternative ways to produce food, aquaculture has become a broadly accepted alternative. However, food quality generated by aquaculture practices is directly","PeriodicalId":402874,"journal":{"name":"Comments on Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115913041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2003-09-01DOI: 10.1080/08865140390450377
M. Rebelo, J. Moreira, M. Moraes, D. Coutinho, J. Torres
The successful use of CYP1A1 as a biomarker of exposure to polynuclear aromatic hydrocarbon in vertebrates lead to a chase for it in marine bivalves. Nevertheless, published results are mostly inconclusive, even with molecular approaches, and there is no clear evidence of a bivalve CYP1A1. Phylogeny of P450 suggests that bivalves could have evolved their own CYP enzymes. Apparently, they even lack the AhR pathway. New sequences from the oyster Crassostrea rhizophorae exhibited little homology to known CYP1A1 but revealed a new CYP2-like gene. Finally, the low activity of the P450 system could be explained by alternative detoxification mechanisms such as the highly active MDR system.
{"title":"Is There a CYP1A1 in Marine Bivalves? Expressed Sequences Related to Cytochrome P450 in Crassostrea Rhizophorae","authors":"M. Rebelo, J. Moreira, M. Moraes, D. Coutinho, J. Torres","doi":"10.1080/08865140390450377","DOIUrl":"https://doi.org/10.1080/08865140390450377","url":null,"abstract":"The successful use of CYP1A1 as a biomarker of exposure to polynuclear aromatic hydrocarbon in vertebrates lead to a chase for it in marine bivalves. Nevertheless, published results are mostly inconclusive, even with molecular approaches, and there is no clear evidence of a bivalve CYP1A1. Phylogeny of P450 suggests that bivalves could have evolved their own CYP enzymes. Apparently, they even lack the AhR pathway. New sequences from the oyster Crassostrea rhizophorae exhibited little homology to known CYP1A1 but revealed a new CYP2-like gene. Finally, the low activity of the P450 system could be explained by alternative detoxification mechanisms such as the highly active MDR system.","PeriodicalId":402874,"journal":{"name":"Comments on Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127368425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2003-09-01DOI: 10.1080/08865140390450368
A. Bainy, M. R. Marques
Chemicals discharged into the environment may be taken up by aquatic organisms and elicit biological responses that can be used as biomarkers of exposure and/or effect. Depending on the site of action, they may be classified as neurotoxic, hepatotoxic, genotoxic, or hemato-immunotoxic biomarkers. Multiple molecular biomarker analysis can furnish a more precise diagnostic of effects induced by different classes of chemicals and provide a sensitive, physiologically based method of determining the presence of a contaminant and its bioavailability to aquatic organisms. This article addresses toxicity, mechanism of adaptation, as well as toxic damage induced by chemical exposure.
{"title":"Global Analysis of Biomarker Responses in Aquatic Organisms Exposed to Contaminants","authors":"A. Bainy, M. R. Marques","doi":"10.1080/08865140390450368","DOIUrl":"https://doi.org/10.1080/08865140390450368","url":null,"abstract":"Chemicals discharged into the environment may be taken up by aquatic organisms and elicit biological responses that can be used as biomarkers of exposure and/or effect. Depending on the site of action, they may be classified as neurotoxic, hepatotoxic, genotoxic, or hemato-immunotoxic biomarkers. Multiple molecular biomarker analysis can furnish a more precise diagnostic of effects induced by different classes of chemicals and provide a sensitive, physiologically based method of determining the presence of a contaminant and its bioavailability to aquatic organisms. This article addresses toxicity, mechanism of adaptation, as well as toxic damage induced by chemical exposure.","PeriodicalId":402874,"journal":{"name":"Comments on Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124904586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2003-09-01DOI: 10.1080/08865140390450395
S. Gorbi, F. Regoli
Formation of reactive oxygen species (ROS) is a natural event for aerobic organisms, but it can be exacerbated by both biological and environmental factors. Cellular oxidative damage is well documented in aquatic organisms, and variations of antioxidants can be sensitive in revealing a pro-oxidant condition. Nonetheless, such effects are difficult to predict according to chemicals, kind of exposure, and species sensitivity. Measuring the overall efficiency of cellular antioxidants toward oxyradicals provides a more integrated assessment of susceptibility of a tissue to oxidative stress. Among the methods for analyzing total antioxidant capacity, the total oxyradical scavenging capacity (TOSC) assay offers the possibility to discriminate different oxyradicals, indicating the roles of these species or their metabolic pathways of formation, in the onset of oxidative disease. The TOSC assay has been widely used on marine organisms under natural and disturbed condition suggesting temporal and causal relationships among increased ROS formation, onset of antioxidant responses, and potential occurrence of oxidative damages and toxicity to cellular targets.
{"title":"Total Oxyradical Scavenging Capacity as an Index of Susceptibility to Oxidative Stress in Marine Organisms","authors":"S. Gorbi, F. Regoli","doi":"10.1080/08865140390450395","DOIUrl":"https://doi.org/10.1080/08865140390450395","url":null,"abstract":"Formation of reactive oxygen species (ROS) is a natural event for aerobic organisms, but it can be exacerbated by both biological and environmental factors. Cellular oxidative damage is well documented in aquatic organisms, and variations of antioxidants can be sensitive in revealing a pro-oxidant condition. Nonetheless, such effects are difficult to predict according to chemicals, kind of exposure, and species sensitivity. Measuring the overall efficiency of cellular antioxidants toward oxyradicals provides a more integrated assessment of susceptibility of a tissue to oxidative stress. Among the methods for analyzing total antioxidant capacity, the total oxyradical scavenging capacity (TOSC) assay offers the possibility to discriminate different oxyradicals, indicating the roles of these species or their metabolic pathways of formation, in the onset of oxidative disease. The TOSC assay has been widely used on marine organisms under natural and disturbed condition suggesting temporal and causal relationships among increased ROS formation, onset of antioxidant responses, and potential occurrence of oxidative damages and toxicity to cellular targets.","PeriodicalId":402874,"journal":{"name":"Comments on Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125584727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2003-09-01DOI: 10.1080/08865140390450386
José María Monserrat, C. E. Rosa, J. Sandrini, L. F. Marins, A. Bianchini, L. Geracitano
Worms like polychaetes, oligochaetes, and nematodes, have been widely used in studies of aquatic and soil pollution. Several ecotoxicological characteristics make these animals suitable for use as a biomonitor, including the fact that these organisms live in close contact with sediments. Also important is that they posses little mobility, which could be useful in biomonitoring programs since it can reflect local environmental problems. Several toxicological aspects are reviewed in these zoological groups, including their antioxidant responses and detoxifying mechanisms of heavy metals. Interestingly, the nematodes and oligochaetes species show induction of proteins different from the well-known metallothionein, including cysteine-rich proteins, and phytochelatins, this last group until recently believed to be present only in plants and fungi.
{"title":"Annelids and Nematodes as Sentinels of Environmental Pollution","authors":"José María Monserrat, C. E. Rosa, J. Sandrini, L. F. Marins, A. Bianchini, L. Geracitano","doi":"10.1080/08865140390450386","DOIUrl":"https://doi.org/10.1080/08865140390450386","url":null,"abstract":"Worms like polychaetes, oligochaetes, and nematodes, have been widely used in studies of aquatic and soil pollution. Several ecotoxicological characteristics make these animals suitable for use as a biomonitor, including the fact that these organisms live in close contact with sediments. Also important is that they posses little mobility, which could be useful in biomonitoring programs since it can reflect local environmental problems. Several toxicological aspects are reviewed in these zoological groups, including their antioxidant responses and detoxifying mechanisms of heavy metals. Interestingly, the nematodes and oligochaetes species show induction of proteins different from the well-known metallothionein, including cysteine-rich proteins, and phytochelatins, this last group until recently believed to be present only in plants and fungi.","PeriodicalId":402874,"journal":{"name":"Comments on Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125808361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2003-05-01DOI: 10.1080/08865140390427445
N. Ballatori, C. Hammond, J. Cunningham
Although the primary physiological role of multidrug resistance-associated protein 2 (MRP2) appears to be the export of a wide variety of organic molecules from the cell, including glutathione disulfide (GSSG) and glutathione S-conjugates, there is now strong evidence that MRP2 also is able to export reduced glutathione (GSH) from the cell. The ability to export both GSH and GSSG would allow MRP2 to contribute directly to the regulation of the cellular thiol-redox status and therefore to the protection against oxidative stress. In addition, because GSH export is intimately linked to the other biological functions of this tripeptide, MRP2 may contribute to the regulation of these other cellular functions. Evidence for a role of MRP2 in GSH export comes from several studies, including (a) studies in MRP2-deficient rats demonstrating that these animals are unable to transport GSH into bile; (b) in vivo and in vitro studies demonstrating that cellular GSH export rates correlate with MRP2 expression levels; (c) comparative studies with the yeast orthologue of MRP2, Ycflp, showing that the yeast orthologue functions as an ATP-driven GSH transporter; (d) direct measurement of ATP-dependent GSH transport in rat liver canalicular membrane vesicles; and (e) studies with MRP1, the functional orthologue of MRP2, demonstrating that MRP1 is able to transport GSH. Taken together these data indicate that GSH is a substrate for MRP2; however, neither the precise biochemical mechanism of transport nor the quantitative significance of this process is yet known.
{"title":"MRP2-Mediated Reduced Glutathione Transport in Protection Against Oxidant Stress","authors":"N. Ballatori, C. Hammond, J. Cunningham","doi":"10.1080/08865140390427445","DOIUrl":"https://doi.org/10.1080/08865140390427445","url":null,"abstract":"Although the primary physiological role of multidrug resistance-associated protein 2 (MRP2) appears to be the export of a wide variety of organic molecules from the cell, including glutathione disulfide (GSSG) and glutathione S-conjugates, there is now strong evidence that MRP2 also is able to export reduced glutathione (GSH) from the cell. The ability to export both GSH and GSSG would allow MRP2 to contribute directly to the regulation of the cellular thiol-redox status and therefore to the protection against oxidative stress. In addition, because GSH export is intimately linked to the other biological functions of this tripeptide, MRP2 may contribute to the regulation of these other cellular functions. Evidence for a role of MRP2 in GSH export comes from several studies, including (a) studies in MRP2-deficient rats demonstrating that these animals are unable to transport GSH into bile; (b) in vivo and in vitro studies demonstrating that cellular GSH export rates correlate with MRP2 expression levels; (c) comparative studies with the yeast orthologue of MRP2, Ycflp, showing that the yeast orthologue functions as an ATP-driven GSH transporter; (d) direct measurement of ATP-dependent GSH transport in rat liver canalicular membrane vesicles; and (e) studies with MRP1, the functional orthologue of MRP2, demonstrating that MRP1 is able to transport GSH. Taken together these data indicate that GSH is a substrate for MRP2; however, neither the precise biochemical mechanism of transport nor the quantitative significance of this process is yet known.","PeriodicalId":402874,"journal":{"name":"Comments on Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123557555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2003-05-01DOI: 10.1080/08865140390427454
M. Treinen-Moslen, L. Kaphalia, M. F. Kanz
MRP2, a multidrug resistance-associated protein, helps to maintain mammalian homeostasis by exporting bilirubin conjugates and many xenobiotics into bile or urine. Experiments with two mutant rat strains, namely TR− and EHBR which have a functionally deficient MRP2, have revealed major alterations in the fate and pathophysiology of substrates for this exporter. Such alterations have clinical implications because multiple conditions, notably sepsis and bile duct obstruction, are associated with diminished expression of the exporter. However, the homeostatic response to MRP2 deficiency is complex since other reported changes in tissues of rats with a mutation in this exporter appear to have compensatory influences on the responses to MRP2 substrates. The goal of this commentary is to describe some representative lessons about the consequences of MRP2 deficiency that have been learned from experiments with the mutant rats. Emphasis will be given to recent observations about the consequences of this deficiency on responses to the NSAID diclofenac, including intestinal ulcers and drug protein adducts in liver, intestine and kidney. Such observations could lead to new strategies for safer therapeutic protocol for drugs whose reactive metabolites are substrates for the MRP2 exporter.
{"title":"Consequences of MRP2 Deficiency: Lessons from Rats with a Mutation in This Exporter","authors":"M. Treinen-Moslen, L. Kaphalia, M. F. Kanz","doi":"10.1080/08865140390427454","DOIUrl":"https://doi.org/10.1080/08865140390427454","url":null,"abstract":"MRP2, a multidrug resistance-associated protein, helps to maintain mammalian homeostasis by exporting bilirubin conjugates and many xenobiotics into bile or urine. Experiments with two mutant rat strains, namely TR− and EHBR which have a functionally deficient MRP2, have revealed major alterations in the fate and pathophysiology of substrates for this exporter. Such alterations have clinical implications because multiple conditions, notably sepsis and bile duct obstruction, are associated with diminished expression of the exporter. However, the homeostatic response to MRP2 deficiency is complex since other reported changes in tissues of rats with a mutation in this exporter appear to have compensatory influences on the responses to MRP2 substrates. The goal of this commentary is to describe some representative lessons about the consequences of MRP2 deficiency that have been learned from experiments with the mutant rats. Emphasis will be given to recent observations about the consequences of this deficiency on responses to the NSAID diclofenac, including intestinal ulcers and drug protein adducts in liver, intestine and kidney. Such observations could lead to new strategies for safer therapeutic protocol for drugs whose reactive metabolites are substrates for the MRP2 exporter.","PeriodicalId":402874,"journal":{"name":"Comments on Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114190084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2003-05-01DOI: 10.1080/08865140390427436
C. Dietrich, A. Geier, R. P. Elferink, S. Matern
Multidrug resistance-associated protein 2 (MRP2, gene nomenclature ABCC2), a member of the family of ATP-binding cassette (ABC-) transporters, is present in the canalicular membrane of hepatocytes and in the apical membrane of enterocytes and renal tubule epithelial cells. At all of these barriers, MRP2 contributes to reduction of the body load of potentially toxic xenobiotics and endogenous waste products. This important “gatekeeper” function of MRP2 has been recognized recently, and data regarding this function are reviewed here. In its function at these barriers, MRP2 is part of a complex detoxification pathway that is regulated by nuclear receptors as common activators. However, MRP2 also can mediate toxicity by concentrating toxicants in the biliary duct and reducing the bioavailability of protective compounds.
{"title":"Defense Barriers in the Body:Contribution of Multidrug Resistance-Associated Protein 2","authors":"C. Dietrich, A. Geier, R. P. Elferink, S. Matern","doi":"10.1080/08865140390427436","DOIUrl":"https://doi.org/10.1080/08865140390427436","url":null,"abstract":"Multidrug resistance-associated protein 2 (MRP2, gene nomenclature ABCC2), a member of the family of ATP-binding cassette (ABC-) transporters, is present in the canalicular membrane of hepatocytes and in the apical membrane of enterocytes and renal tubule epithelial cells. At all of these barriers, MRP2 contributes to reduction of the body load of potentially toxic xenobiotics and endogenous waste products. This important “gatekeeper” function of MRP2 has been recognized recently, and data regarding this function are reviewed here. In its function at these barriers, MRP2 is part of a complex detoxification pathway that is regulated by nuclear receptors as common activators. However, MRP2 also can mediate toxicity by concentrating toxicants in the biliary duct and reducing the bioavailability of protective compounds.","PeriodicalId":402874,"journal":{"name":"Comments on Toxicology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"113980496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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