Pub Date : 2021-04-19DOI: 10.2174/1874340402107010008
Takeo Takeda, Masahiro Ogawa, J. Kitamoto, Takahiro Kyoya, M. Terada
Hyperglycemia, blood glucose levels above 2.0 g/L, is one of the major pathophysiological factors causing late complications in diabetes [1, 2]. Reactive Oxygen Species (ROS) are increased by hyperglycemia [3]. Oxidative damage in individual cells may reach a sufficient threshold to cause DNA strand breaks and induce cell death [4]. Therefore, hyperglycemia-induced oxidative stress is one of the responsible factors for the pathology of diabetic complications.
{"title":"High Glucose Enhances Skin Sensitizer-induced NRF2 Activation In Vitro","authors":"Takeo Takeda, Masahiro Ogawa, J. Kitamoto, Takahiro Kyoya, M. Terada","doi":"10.2174/1874340402107010008","DOIUrl":"https://doi.org/10.2174/1874340402107010008","url":null,"abstract":"Hyperglycemia, blood glucose levels above 2.0 g/L, is one of the major pathophysiological factors causing late complications in diabetes [1, 2]. Reactive Oxygen Species (ROS) are increased by hyperglycemia [3]. Oxidative damage in individual cells may reach a sufficient threshold to cause DNA strand breaks and induce cell death [4]. Therefore, hyperglycemia-induced oxidative stress is one of the responsible factors for the pathology of diabetic complications.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"5 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85665624","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 : 2021-03-02DOI: 10.2174/1874340402107010001
M. Errasfa
The COVID-19 pandemic is challenging world health authorities and researchers. WHO is supervising many clinical studies to ascertain whether some known drugs can be effective against the disease. Meanwhile, researchers around the globe are working on cellular and molecular mechanisms that are key steps of SARS-Cov-2 associated infection. Blood hemostasis dysfunction, inflammation, hypoxia and venous thrombotic events are reported to be involved in the pathophysiology of COVID-19 patients at early and late severe stages of the disease. It is of high relevance to understand how SARS-Cov-2 triggers negative cellular and biochemical events in infected persons. A large number of cell species and active molecules, such as blood and tissue enzymes, cytokines, and other active amines and lipid inflammatory molecular species, can be involved in immune reactions and host defense mechanisms upon human infectious diseases or other kinds of health issues such as trauma or snake envenomation. Possible physiopathology trends of COVID-19 and some therapeutic perspectives are discussed in the present minireview.
{"title":"Blood Hemostasis Dysfunction and Inflammation in COVID-19 Patients: Viral and Host Active Molecules as Therapeutic Targets","authors":"M. Errasfa","doi":"10.2174/1874340402107010001","DOIUrl":"https://doi.org/10.2174/1874340402107010001","url":null,"abstract":"The COVID-19 pandemic is challenging world health authorities and researchers. WHO is supervising many clinical studies to ascertain whether some known drugs can be effective against the disease. Meanwhile, researchers around the globe are working on cellular and molecular mechanisms that are key steps of SARS-Cov-2 associated infection. Blood hemostasis dysfunction, inflammation, hypoxia and venous thrombotic events are reported to be involved in the pathophysiology of COVID-19 patients at early and late severe stages of the disease. It is of high relevance to understand how SARS-Cov-2 triggers negative cellular and biochemical events in infected persons. A large number of cell species and active molecules, such as blood and tissue enzymes, cytokines, and other active amines and lipid inflammatory molecular species, can be involved in immune reactions and host defense mechanisms upon human infectious diseases or other kinds of health issues such as trauma or snake envenomation. Possible physiopathology trends of COVID-19 and some therapeutic perspectives are discussed in the present minireview.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"158 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2021-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79972366","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 : 2013-05-30DOI: 10.2174/1874340401306010027
V. Bianchi, A. Raspagni, C. Arfini
Alcohol-related problems are typically associated with medical, economic and social issues. The reduction of the problem can only occur if effective strategies to prevent, diagnose and treat alcohol abuse are developed. Real help could come from laboratory tests that represent objective evidence of alcohol problems. Authors present new biomarkers as Carbohydrate-deficient transferrin (CDT), Ethyl Glucuronide and Ethyl Sulfate ( EtG and EtS)), Fatty Acids Ethyl Esters (FAEE) anf Phosphatidy ethanol (PEth) in differents biological samples.
{"title":"Emerging Biomarkers of Alcohol Consumption: Clinical and Forensic Applications","authors":"V. Bianchi, A. Raspagni, C. Arfini","doi":"10.2174/1874340401306010027","DOIUrl":"https://doi.org/10.2174/1874340401306010027","url":null,"abstract":"Alcohol-related problems are typically associated with medical, economic and social issues. The reduction of the problem can only occur if effective strategies to prevent, diagnose and treat alcohol abuse are developed. Real help could come from laboratory tests that represent objective evidence of alcohol problems. Authors present new biomarkers as Carbohydrate-deficient transferrin (CDT), Ethyl Glucuronide and Ethyl Sulfate ( EtG and EtS)), Fatty Acids Ethyl Esters (FAEE) anf Phosphatidy ethanol (PEth) in differents biological samples.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"47 1","pages":"27-33"},"PeriodicalIF":0.0,"publicationDate":"2013-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89322004","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 : 2013-05-30DOI: 10.2174/1874340401306010020
M. Zilli
This paper would provide the analyst with an easy to use step-by-step guide to calculate the uncertainty of measurement in implementing a new analytical method. There are two main ways to attain such an achievement. The first is to consider all the possible sources of variability and then to sum up all of them in the final calculation. The second is taking part in a collaborative trial and processing the resulting statistics. Both methods imply different advantages and drawbacks. It is up the analyst to choose the one fits best his requirements. Anyway it is nearly inescapable providing, along with the test result, its own uncertainty. This entire subject is stated by a standard well known to those who practise the profession of a chemical analyst, which is the UNI CEI EN ISO/IEC 17025:2005. This standard has been imposed by the European Community for matters concerning food and environmental surveillance, but it has also become part of the guidelines of several National Associations of Clinical Toxicology. This standard pledges the analyst to use validated analytical methods, issued by one of the national or international Standards Organizations or, at least, by an internationally acknowledged Scientific Society.
本文将为分析人员在实施一种新的分析方法时计算测量不确定度提供一个易于使用的分步指南。有两种主要方法可以达到这样的成就。第一种方法是考虑所有可能的变率来源，然后在最后的计算中把所有的变率来源加起来。第二种是参与合作试验，并处理由此产生的统计数据。两种方法都有不同的优点和缺点。这取决于分析师选择一个最适合他的需求。无论如何，随着测试结果的出现，它几乎不可避免地提供了自身的不确定性。这整个主题是由那些从事化学分析专业的人所熟知的标准来陈述的，这就是UNI CEI EN ISO/IEC 17025:2005。这一标准由欧共体用于食品和环境监测，但它也成为几个国家临床毒理学协会指导方针的一部分。本标准保证分析人员使用由国家或国际标准组织或至少由国际公认的科学学会发布的经过验证的分析方法。
{"title":"A Practical Guide to the Calculation of Uncertainty of Measurement","authors":"M. Zilli","doi":"10.2174/1874340401306010020","DOIUrl":"https://doi.org/10.2174/1874340401306010020","url":null,"abstract":"This paper would provide the analyst with an easy to use step-by-step guide to calculate the uncertainty of measurement in implementing a new analytical method. There are two main ways to attain such an achievement. The first is to consider all the possible sources of variability and then to sum up all of them in the final calculation. The second is taking part in a collaborative trial and processing the resulting statistics. Both methods imply different advantages and drawbacks. It is up the analyst to choose the one fits best his requirements. Anyway it is nearly inescapable providing, along with the test result, its own uncertainty. This entire subject is stated by a standard well known to those who practise the profession of a chemical analyst, which is the UNI CEI EN ISO/IEC 17025:2005. This standard has been imposed by the European Community for matters concerning food and environmental surveillance, but it has also become part of the guidelines of several National Associations of Clinical Toxicology. This standard pledges the analyst to use validated analytical methods, issued by one of the national or international Standards Organizations or, at least, by an internationally acknowledged Scientific Society.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"44 1","pages":"20-26"},"PeriodicalIF":0.0,"publicationDate":"2013-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77823342","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 : 2013-05-30DOI: 10.2174/1874340401306010034
Giorgio Cerizza, M. Ranalletti
Short residential rehabilitation in the treatment of alcohol dependence in Italy is becoming more widespread
在意大利，短期住院康复治疗酒精依赖的做法越来越普遍
{"title":"Residential Treatment as a Rehabilitation Opportunity for Alcoholism Care","authors":"Giorgio Cerizza, M. Ranalletti","doi":"10.2174/1874340401306010034","DOIUrl":"https://doi.org/10.2174/1874340401306010034","url":null,"abstract":"Short residential rehabilitation in the treatment of alcohol dependence in Italy is becoming more widespread","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"1 1","pages":"34-37"},"PeriodicalIF":0.0,"publicationDate":"2013-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88197985","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 : 2013-05-30DOI: 10.2174/1874340401306010013
L. Desinan, A. Colatutto, P. Sala
In forensic toxicology the main relevant scope of toxicologist is to answer these following questions: which kind of drug is involved? Is the analytical result related to death? Which is the supposed lethal dose? Despite the technological improvement in laboratory medicine, the main questions are apparently unresolved, because the availability of new laboratory instrumentation has sometimes increased the complexity of the medical examiner task. In post mortem toxicology the medical examiner's and the toxicologist's role is constantly challenged by analytical, methodological, circumstantial problems, and only the single professional experience can help to find which drug is involved. In our experience the only way to avoid, or limit, mistakes is to follow strictly a Search Strategy, which combines single professional experience, circumstantial data and a correct and a punctual manner of sampling from corpses. The most complete and proper tissue sampling from autopsy is mandatory for the whole diagnostic process. This approach in synergy with the pathologist and toxicologist dialogue can help the medical examiner to avoid mistakes and positively infer the whole diagnostic process.
{"title":"The Relevance of Synergy Between Forensic Pathologist and Toxicologist in Medico-Legal Autopsies","authors":"L. Desinan, A. Colatutto, P. Sala","doi":"10.2174/1874340401306010013","DOIUrl":"https://doi.org/10.2174/1874340401306010013","url":null,"abstract":"In forensic toxicology the main relevant scope of toxicologist is to answer these following questions: which kind of drug is involved? Is the analytical result related to death? Which is the supposed lethal dose? Despite the technological improvement in laboratory medicine, the main questions are apparently unresolved, because the availability of new laboratory instrumentation has sometimes increased the complexity of the medical examiner task. In post mortem toxicology the medical examiner's and the toxicologist's role is constantly challenged by analytical, methodological, circumstantial problems, and only the single professional experience can help to find which drug is involved. In our experience the only way to avoid, or limit, mistakes is to follow strictly a Search Strategy, which combines single professional experience, circumstantial data and a correct and a punctual manner of sampling from corpses. The most complete and proper tissue sampling from autopsy is mandatory for the whole diagnostic process. This approach in synergy with the pathologist and toxicologist dialogue can help the medical examiner to avoid mistakes and positively infer the whole diagnostic process.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"72 1","pages":"13-19"},"PeriodicalIF":0.0,"publicationDate":"2013-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84493899","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 : 2013-05-30DOI: 10.2174/1874340401306010011
A. Colatutto
It is nevertheless not easy to define the borders between Pharmacology and Toxicology too, because the side effects of commonly used therapies could be extremely toxic, the effects of the Drug of Abuse are also toxic, and toxic substances could be found in soil, water and air. It is well known that Medicine is “rapidly changing in rapidly changing world”, but the paramount progress in laboratory technology has positively influenced the whole Medicine diagnostic process and practice. For these reasons a rational diagnostic strategy is mandatory to optimize the resources. The aim of the toxicological analysis is firstly to detect the toxicant, and to fulfill this scope so that the toxicologist can take advantage of improved technology. Even if new screening methods are easy to perform, highly automated and fit not only for highly specialized laboratory staff, confirmation analysis needs more sophisticated and extremely expensive technology. It is well known indeed that confirmation tests should be performed only by chromatographic technology, both gas chromatographic and liquid chromatographic coupled with mass spectrometry, and these kinds of tests need highly specialized personnel.
{"title":"Key Role of the Rational Laboratory Strategy in Diagnostic, Analytical and Forensic Toxicology","authors":"A. Colatutto","doi":"10.2174/1874340401306010011","DOIUrl":"https://doi.org/10.2174/1874340401306010011","url":null,"abstract":"It is nevertheless not easy to define the borders between Pharmacology and Toxicology too, because the side effects of commonly used therapies could be extremely toxic, the effects of the Drug of Abuse are also toxic, and toxic substances could be found in soil, water and air. It is well known that Medicine is “rapidly changing in rapidly changing world”, but the paramount progress in laboratory technology has positively influenced the whole Medicine diagnostic process and practice. For these reasons a rational diagnostic strategy is mandatory to optimize the resources. The aim of the toxicological analysis is firstly to detect the toxicant, and to fulfill this scope so that the toxicologist can take advantage of improved technology. Even if new screening methods are easy to perform, highly automated and fit not only for highly specialized laboratory staff, confirmation analysis needs more sophisticated and extremely expensive technology. It is well known indeed that confirmation tests should be performed only by chromatographic technology, both gas chromatographic and liquid chromatographic coupled with mass spectrometry, and these kinds of tests need highly specialized personnel.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"19 1","pages":"11-12"},"PeriodicalIF":0.0,"publicationDate":"2013-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73332813","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 : 2013-04-19DOI: 10.2174/1874340401205010001
Shakuntala Kondraganti, R. König, P. Boor, Shahnawaz Khan, B. Kaphalia, M. Khan, G. Ansari
Aflatoxicosis mostly leads to serious clinical signs of malnutrition, growth retardation, and impairment of utilization of nutrients, immunosupression, liver diseases and cancer. Detoxification or prevention of such toxicity is interesting to researchers in change field. In pursuit for an approach, the synthetic copper(I)- nicotinate complex has been evaluated against the traditional Butylated hydroxy toluene (BHT) for possible protective effects as a food additive in induced aflatoxicosed animals. Induction of toxicity in adult rats by AFB1 60 µg/kg body weight divided on three times a week for consecutive five weeks resulted in marked hepatic necrosis, collagen fibers around portal tract and iron deposits as well as features of general cellular collapse and cirrhosis. The protective effects were tested on two animal groups by associate doses of BHT (0.05 mg / kg B.W.) in one group and copper (I) nicotinate complex (0.4 mg/kg B.W.) in the other. Results showed, in both groups, almost normal histological as well as biochemical markers especially those treated with the copper complex, which suggests that anti-inflammatory copper complex can be used as a protective agent against aflatoxicosis when used in doses resemble those used in pharmaceutical vitamin supplements.
{"title":"Mechanistic evaluation of trichloroethene-mediated autoimmune hepatitis-like disease in female MRL+/+ Mice","authors":"Shakuntala Kondraganti, R. König, P. Boor, Shahnawaz Khan, B. Kaphalia, M. Khan, G. Ansari","doi":"10.2174/1874340401205010001","DOIUrl":"https://doi.org/10.2174/1874340401205010001","url":null,"abstract":"Aflatoxicosis mostly leads to serious clinical signs of malnutrition, growth retardation, and impairment of utilization of nutrients, immunosupression, liver diseases and cancer. Detoxification or prevention of such toxicity is interesting to researchers in change field. In pursuit for an approach, the synthetic copper(I)- nicotinate complex has been evaluated against the traditional Butylated hydroxy toluene (BHT) for possible protective effects as a food additive in induced aflatoxicosed animals. Induction of toxicity in adult rats by AFB1 60 µg/kg body weight divided on three times a week for consecutive five weeks resulted in marked hepatic necrosis, collagen fibers around portal tract and iron deposits as well as features of general cellular collapse and cirrhosis. The protective effects were tested on two animal groups by associate doses of BHT (0.05 mg / kg B.W.) in one group and copper (I) nicotinate complex (0.4 mg/kg B.W.) in the other. Results showed, in both groups, almost normal histological as well as biochemical markers especially those treated with the copper complex, which suggests that anti-inflammatory copper complex can be used as a protective agent against aflatoxicosis when used in doses resemble those used in pharmaceutical vitamin supplements.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"15 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2013-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73663773","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 : 2012-12-28DOI: 10.2174/1874340401205010021
J. McCluskey, Stephen C Harbison, D. Sava, G. Johnson, R. Harbison
Cocaine abuse is associated with multiple health problems including occasional hepatic failure and death. The mechanism of cocaine-induced hepatotoxicity (CIH) is not clear, although studies in mice have demonstrated that cocaine-induced liver injury may be mediated by nitric oxide and reactive oxygen species. Recently, we have found that cocaine increases poly (ADP-ribose) polymerase (PARP) activity in the liver. Therefore, inhibition of PARP may block CIH. A preliminary assessment of the PARP inhibitor 3,4-Dihydro-5-(4-(1-piperidinyl)butoxyl)-1(2H)-isoquinolinone (DPQ) in ICR mice failed to attenuate CIH. However, the PARP inhibitor 1,5-dihydroxyisoquinoline (DIQ) successfully attenuated CIH. Mean ALT activity of 569 IU caused by cocaine treatment alone, was limited to 79 IU in ICR mice concomitantly treated with DIQ (10 mg/kg, ip). The protective effect of DIQ was also associated with prevention of development of lipid peroxidation in liver tissue, reduced depletion of glutathione (GSH), and a reduced production of nitrites. Cocaine-induced TBARS was significantly decreased by DIQ from a mean of 5.7 nmol/mg protein to a mean of 2.5 nmol/mg protein, similar to untreated mice. Hepatic GSH was reduced more than 2 fold following cocaine administration but treatment with DIQ conserved GSH at the level of untreated mice. The protective effect of DIQ in attenuating CIH can potentially be explained by the dual inhibitory effect of DIQ that reduces induction of PARP and inducible nitric oxide synthetase (iNOS). The DIQ attenuation of CIH provides evidence for a PARP and iNOS modulated mechanism of action for this hepatocellular pathology.
{"title":"PARP-1 Inhibitor Attenuates Cocaine-Induced Hepatotoxicity","authors":"J. McCluskey, Stephen C Harbison, D. Sava, G. Johnson, R. Harbison","doi":"10.2174/1874340401205010021","DOIUrl":"https://doi.org/10.2174/1874340401205010021","url":null,"abstract":"Cocaine abuse is associated with multiple health problems including occasional hepatic failure and death. The mechanism of cocaine-induced hepatotoxicity (CIH) is not clear, although studies in mice have demonstrated that cocaine-induced liver injury may be mediated by nitric oxide and reactive oxygen species. Recently, we have found that cocaine increases poly (ADP-ribose) polymerase (PARP) activity in the liver. Therefore, inhibition of PARP may block CIH. A preliminary assessment of the PARP inhibitor 3,4-Dihydro-5-(4-(1-piperidinyl)butoxyl)-1(2H)-isoquinolinone (DPQ) in ICR mice failed to attenuate CIH. However, the PARP inhibitor 1,5-dihydroxyisoquinoline (DIQ) successfully attenuated CIH. Mean ALT activity of 569 IU caused by cocaine treatment alone, was limited to 79 IU in ICR mice concomitantly treated with DIQ (10 mg/kg, ip). The protective effect of DIQ was also associated with prevention of development of lipid peroxidation in liver tissue, reduced depletion of glutathione (GSH), and a reduced production of nitrites. Cocaine-induced TBARS was significantly decreased by DIQ from a mean of 5.7 nmol/mg protein to a mean of 2.5 nmol/mg protein, similar to untreated mice. Hepatic GSH was reduced more than 2 fold following cocaine administration but treatment with DIQ conserved GSH at the level of untreated mice. The protective effect of DIQ in attenuating CIH can potentially be explained by the dual inhibitory effect of DIQ that reduces induction of PARP and inducible nitric oxide synthetase (iNOS). The DIQ attenuation of CIH provides evidence for a PARP and iNOS modulated mechanism of action for this hepatocellular pathology.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"48 1","pages":"21-27"},"PeriodicalIF":0.0,"publicationDate":"2012-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84164019","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 : 2012-10-19DOI: 10.2174/1874340401205010011
Ilka Elizma Schroeder, J. J. V. Tonder, V. Steenkamp
The organochlorine compound, pentachlorophenol (PCP), is classified as a hazardous substance. Its metabolite, tetrachloro-1,2-hydroquinone (TCHQ), has been detected in occupationally-exposed subjects and can readily be converted to tetrachloro-1,4-benzoquinone (TCBQ) under physiological conditions. Hazard characterization has previously identified the liver as the target organ of PCP toxicity in rats and dogs and as the liver is the major site of metabolism of the parent compound, this raises concern for the effects that the metabolites of PCP may have on the liver. Although the hepatotoxic effects of PCP have been described, less is known about the effects of its metabolites on hepatocyte function. Studying the effects of these metabolites on hepatocytes may provide valuable information regarding the effects that these compounds could exert on the liver itself and allude to the clinical manifestations of toxicity that can be expected. The aim of this study was therefore to assess the effect of PCP, TCHQ and TCBQ on the following cellular parameters: cell viability, mitochondrial membrane potential and intracellular ROS formation, as indicators of hepatocyte homeostasis. Both PCP and its metabolites, TCHQ and TCBQ decreased cell viability with IC 50 of 68.05, 129.40 and 144.00 ∝M, respectively. All three compounds caused mitochondrial depolarization, with the effect being more profound following exposure to TCHQ and TCBQ. PCP did not induce any ROS generation, whereas TCHQ and TCBQ produced extensive ROS. Findings from this study suggest that in hepatocytes the mechanism of toxicity of PCP differs from that of its metabolites, TCHQ and TCBQ.
{"title":"Comparative toxicity of pentachlorophenol with its metabolites tetrachloro-1,2-hydroquinone and tetrachloro-1,4-benzoquinone in HepG2 cells","authors":"Ilka Elizma Schroeder, J. J. V. Tonder, V. Steenkamp","doi":"10.2174/1874340401205010011","DOIUrl":"https://doi.org/10.2174/1874340401205010011","url":null,"abstract":"The organochlorine compound, pentachlorophenol (PCP), is classified as a hazardous substance. Its metabolite, tetrachloro-1,2-hydroquinone (TCHQ), has been detected in occupationally-exposed subjects and can readily be converted to tetrachloro-1,4-benzoquinone (TCBQ) under physiological conditions. Hazard characterization has previously identified the liver as the target organ of PCP toxicity in rats and dogs and as the liver is the major site of metabolism of the parent compound, this raises concern for the effects that the metabolites of PCP may have on the liver. Although the hepatotoxic effects of PCP have been described, less is known about the effects of its metabolites on hepatocyte function. Studying the effects of these metabolites on hepatocytes may provide valuable information regarding the effects that these compounds could exert on the liver itself and allude to the clinical manifestations of toxicity that can be expected. The aim of this study was therefore to assess the effect of PCP, TCHQ and TCBQ on the following cellular parameters: cell viability, mitochondrial membrane potential and intracellular ROS formation, as indicators of hepatocyte homeostasis. Both PCP and its metabolites, TCHQ and TCBQ decreased cell viability with IC 50 of 68.05, 129.40 and 144.00 ∝M, respectively. All three compounds caused mitochondrial depolarization, with the effect being more profound following exposure to TCHQ and TCBQ. PCP did not induce any ROS generation, whereas TCHQ and TCBQ produced extensive ROS. Findings from this study suggest that in hepatocytes the mechanism of toxicity of PCP differs from that of its metabolites, TCHQ and TCBQ.","PeriodicalId":22859,"journal":{"name":"The Open Toxicology Journal","volume":"73 1","pages":"11-20"},"PeriodicalIF":0.0,"publicationDate":"2012-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86095990","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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