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Mechanisms of hepatotoxicity of chloroacetonitrile - an end product of water chlorination

Chloroacetonitrile is a disinfectant by-product of chlorination of drinking water and is considered as a direct-acting mutagenic and carcinogenic agent. Time-course and dose-response studies were performed to examine the mechanism of chloroacetonitrile-induced hepatotoxicity. In the time-course stud...

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Published in:Pakistan journal of pharmaceutical sciences 2013-01, Vol.26 (1), p.145
Main Authors: Abo-Salem, Osama Mohamed, Ghonaim, Mabrouk Mahmoud, Al-Zahrani, Saad Salem
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description Chloroacetonitrile is a disinfectant by-product of chlorination of drinking water and is considered as a direct-acting mutagenic and carcinogenic agent. Time-course and dose-response studies were performed to examine the mechanism of chloroacetonitrile-induced hepatotoxicity. In the time-course study, animals were scarified at 2, 4, 6 and 12 h after a single oral dose of chloroacetonitrile (38 mg/kg, p.o.). In the dose-response study, rats were scarified at 2 h after a single oral dose of chloroacetonitrile (9, 19, 38, and 76 mg/kg). In the time-course study chloroacetonitrile induced a significant decrease of hepatic glutathione, and activities of glutathione-S-transferase, glutathione proxidase and superoxide dismutase accompanied with an increase of hepatic malondialdehyde, plasma cytokines (IL-6 & 10 and TNF-α), serum aminotransferases and total bilirubin after 2 h of administration. Maximal alteration of the estimated parameters was observed at 4 h and returned to normal value at 6 h and/or 12 h after chloroacetonitrile treatment. Moreover, the alterations in oxidant, antioxidant parameters, inflammatory cytokines and the liver function tests were dose dependant. Histopathological findings supported the biochemical results. These data indicate that the mechanism of chloroacetonitrile-induced hepatotoxicity may be mediated through depletion of antioxidants, induction of oxidative stress and inflammatory cytokines.
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Time-course and dose-response studies were performed to examine the mechanism of chloroacetonitrile-induced hepatotoxicity. In the time-course study, animals were scarified at 2, 4, 6 and 12 h after a single oral dose of chloroacetonitrile (38 mg/kg, p.o.). In the dose-response study, rats were scarified at 2 h after a single oral dose of chloroacetonitrile (9, 19, 38, and 76 mg/kg). In the time-course study chloroacetonitrile induced a significant decrease of hepatic glutathione, and activities of glutathione-S-transferase, glutathione proxidase and superoxide dismutase accompanied with an increase of hepatic malondialdehyde, plasma cytokines (IL-6 &amp; 10 and TNF-α), serum aminotransferases and total bilirubin after 2 h of administration. Maximal alteration of the estimated parameters was observed at 4 h and returned to normal value at 6 h and/or 12 h after chloroacetonitrile treatment. Moreover, the alterations in oxidant, antioxidant parameters, inflammatory cytokines and the liver function tests were dose dependant. Histopathological findings supported the biochemical results. 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Time-course and dose-response studies were performed to examine the mechanism of chloroacetonitrile-induced hepatotoxicity. In the time-course study, animals were scarified at 2, 4, 6 and 12 h after a single oral dose of chloroacetonitrile (38 mg/kg, p.o.). In the dose-response study, rats were scarified at 2 h after a single oral dose of chloroacetonitrile (9, 19, 38, and 76 mg/kg). In the time-course study chloroacetonitrile induced a significant decrease of hepatic glutathione, and activities of glutathione-S-transferase, glutathione proxidase and superoxide dismutase accompanied with an increase of hepatic malondialdehyde, plasma cytokines (IL-6 &amp; 10 and TNF-α), serum aminotransferases and total bilirubin after 2 h of administration. Maximal alteration of the estimated parameters was observed at 4 h and returned to normal value at 6 h and/or 12 h after chloroacetonitrile treatment. Moreover, the alterations in oxidant, antioxidant parameters, inflammatory cytokines and the liver function tests were dose dependant. Histopathological findings supported the biochemical results. 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Ghonaim, Mabrouk Mahmoud ; Al-Zahrani, Saad Salem</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g250t-58fab7ccb989cd1d953889d154bda17374860f136505d6c06b6d4c33d1d788693</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acetonitrile</topic><topic>Acetonitriles - toxicity</topic><topic>Animals</topic><topic>Bilirubin - blood</topic><topic>Chemical and Drug Induced Liver Injury - etiology</topic><topic>Chemical and Drug Induced Liver Injury - immunology</topic><topic>Chemical and Drug Induced Liver Injury - metabolism</topic><topic>Chemical and Drug Induced Liver Injury - pathology</topic><topic>Chemical properties</topic><topic>Chlorination</topic><topic>Composition</topic><topic>Cytokines - blood</topic><topic>Disinfection and disinfectants</topic><topic>Dose-Response Relationship, Drug</topic><topic>Glutathione - metabolism</topic><topic>Glutathione Peroxidase - metabolism</topic><topic>Glutathione Transferase - metabolism</topic><topic>Identification and classification</topic><topic>Inflammation Mediators - blood</topic><topic>Liver - drug effects</topic><topic>Liver - immunology</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Liver Function Tests</topic><topic>Male</topic><topic>Malondialdehyde - metabolism</topic><topic>Oxidative Stress - drug effects</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Superoxide Dismutase - metabolism</topic><topic>Time Factors</topic><topic>Transaminases - blood</topic><topic>Water chemistry</topic><topic>Water Pollutants, Chemical - toxicity</topic><topic>Water Purification</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Abo-Salem, Osama Mohamed</creatorcontrib><creatorcontrib>Ghonaim, Mabrouk Mahmoud</creatorcontrib><creatorcontrib>Al-Zahrani, Saad Salem</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Pakistan journal of pharmaceutical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Abo-Salem, Osama Mohamed</au><au>Ghonaim, Mabrouk Mahmoud</au><au>Al-Zahrani, Saad Salem</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mechanisms of hepatotoxicity of chloroacetonitrile - an end product of water chlorination</atitle><jtitle>Pakistan journal of pharmaceutical sciences</jtitle><addtitle>Pak J Pharm Sci</addtitle><date>2013-01</date><risdate>2013</risdate><volume>26</volume><issue>1</issue><spage>145</spage><pages>145-</pages><issn>1011-601X</issn><abstract>Chloroacetonitrile is a disinfectant by-product of chlorination of drinking water and is considered as a direct-acting mutagenic and carcinogenic agent. Time-course and dose-response studies were performed to examine the mechanism of chloroacetonitrile-induced hepatotoxicity. In the time-course study, animals were scarified at 2, 4, 6 and 12 h after a single oral dose of chloroacetonitrile (38 mg/kg, p.o.). In the dose-response study, rats were scarified at 2 h after a single oral dose of chloroacetonitrile (9, 19, 38, and 76 mg/kg). In the time-course study chloroacetonitrile induced a significant decrease of hepatic glutathione, and activities of glutathione-S-transferase, glutathione proxidase and superoxide dismutase accompanied with an increase of hepatic malondialdehyde, plasma cytokines (IL-6 &amp; 10 and TNF-α), serum aminotransferases and total bilirubin after 2 h of administration. Maximal alteration of the estimated parameters was observed at 4 h and returned to normal value at 6 h and/or 12 h after chloroacetonitrile treatment. Moreover, the alterations in oxidant, antioxidant parameters, inflammatory cytokines and the liver function tests were dose dependant. Histopathological findings supported the biochemical results. These data indicate that the mechanism of chloroacetonitrile-induced hepatotoxicity may be mediated through depletion of antioxidants, induction of oxidative stress and inflammatory cytokines.</abstract><cop>Pakistan</cop><pub>Pakistan Journal of Pharmaceutical Sciences</pub><pmid>23261740</pmid></addata></record>
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subjects Acetonitrile
Acetonitriles - toxicity
Animals
Bilirubin - blood
Chemical and Drug Induced Liver Injury - etiology
Chemical and Drug Induced Liver Injury - immunology
Chemical and Drug Induced Liver Injury - metabolism
Chemical and Drug Induced Liver Injury - pathology
Chemical properties
Chlorination
Composition
Cytokines - blood
Disinfection and disinfectants
Dose-Response Relationship, Drug
Glutathione - metabolism
Glutathione Peroxidase - metabolism
Glutathione Transferase - metabolism
Identification and classification
Inflammation Mediators - blood
Liver - drug effects
Liver - immunology
Liver - metabolism
Liver - pathology
Liver Function Tests
Male
Malondialdehyde - metabolism
Oxidative Stress - drug effects
Rats
Rats, Wistar
Superoxide Dismutase - metabolism
Time Factors
Transaminases - blood
Water chemistry
Water Pollutants, Chemical - toxicity
Water Purification
title Mechanisms of hepatotoxicity of chloroacetonitrile - an end product of water chlorination
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