The role of enzyme induction and inhibition on cypermethrin hepatotoxicity
Cypermethrin at different concentrations (100, 200, 400 and 800 ng ml−1) was incubated with a primary culture of rat hepatocytes. Cypermethrin was cytotoxic to rat hepatocytes at concentrations of 200 ng ml−1or greater. Toxicity was measured by a decrease in cell viability and leakage of ALT and AST...
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| Veröffentlicht in: | Pharmacological research 2001-07, Vol.44 (1), p.33-39 |
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| creator | El-tawil, Osama S. Abdel-rahman, Mohamed S. |
| description | Cypermethrin at different concentrations (100, 200, 400 and 800 ng ml−1) was incubated with a primary culture of rat hepatocytes. Cypermethrin was cytotoxic to rat hepatocytes at concentrations of 200 ng ml−1or greater. Toxicity was measured by a decrease in cell viability and leakage of ALT and AST enzymes into the culture medium. The role of cytochrome P450 in the hepatotoxicity of cypermethrin insecticide was investigated in fresh hepatocytes isolated either from phenobarbital pretreated rats or control rats and coincubated with SKF525A. Pretreatment with phenobarbital strongly protected the hepatocytes against the cypermethrin induced loss of cell viability percentage and increased enzyme leakage percentage. Coincubation of the hepatocytes with SKF525A, a well-known cytochrome P450 inhibitor, substantially potentiated the effect of cypermethrin on cell viability and enzyme leakage. These results suggest that the cytocidal hepatotoxicity of cypermethrin in primary hepatocyte culture depends on its parent compound and phenobarbital, as a cytochrome P450 inducer, could be of therapeutic value. |
| doi_str_mv | 10.1006/phrs.2001.0826 |
| format | Article |
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Cypermethrin was cytotoxic to rat hepatocytes at concentrations of 200 ng ml−1or greater. Toxicity was measured by a decrease in cell viability and leakage of ALT and AST enzymes into the culture medium. The role of cytochrome P450 in the hepatotoxicity of cypermethrin insecticide was investigated in fresh hepatocytes isolated either from phenobarbital pretreated rats or control rats and coincubated with SKF525A. Pretreatment with phenobarbital strongly protected the hepatocytes against the cypermethrin induced loss of cell viability percentage and increased enzyme leakage percentage. Coincubation of the hepatocytes with SKF525A, a well-known cytochrome P450 inhibitor, substantially potentiated the effect of cypermethrin on cell viability and enzyme leakage. 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Cypermethrin was cytotoxic to rat hepatocytes at concentrations of 200 ng ml−1or greater. Toxicity was measured by a decrease in cell viability and leakage of ALT and AST enzymes into the culture medium. The role of cytochrome P450 in the hepatotoxicity of cypermethrin insecticide was investigated in fresh hepatocytes isolated either from phenobarbital pretreated rats or control rats and coincubated with SKF525A. Pretreatment with phenobarbital strongly protected the hepatocytes against the cypermethrin induced loss of cell viability percentage and increased enzyme leakage percentage. Coincubation of the hepatocytes with SKF525A, a well-known cytochrome P450 inhibitor, substantially potentiated the effect of cypermethrin on cell viability and enzyme leakage. These results suggest that the cytocidal hepatotoxicity of cypermethrin in primary hepatocyte culture depends on its parent compound and phenobarbital, as a cytochrome P450 inducer, could be of therapeutic value.</description><subject>Alanine Transaminase - drug effects</subject><subject>Alanine Transaminase - metabolism</subject><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Aspartate Aminotransferases - drug effects</subject><subject>Aspartate Aminotransferases - metabolism</subject><subject>Cell Survival - drug effects</subject><subject>Cells, Cultured</subject><subject>cypermethrin mechanism of action, synthetic pyrethroids, hepatotoxicity</subject><subject>Enzyme Activators - pharmacology</subject><subject>Enzyme Induction - drug effects</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Hepatocytes - drug effects</subject><subject>Hepatocytes - enzymology</subject><subject>Hepatocytes - metabolism</subject><subject>Insecticides - metabolism</subject><subject>Insecticides - toxicity</subject><subject>Male</subject><subject>Phenobarbital - pharmacology</subject><subject>Proadifen - pharmacology</subject><subject>Pyrethrins - metabolism</subject><subject>Pyrethrins - toxicity</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><issn>1043-6618</issn><issn>1096-1186</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kM1LxDAQxYMo7rp69Sj9B1onaTZJj7L4yYKX9RyaZEoj2w_SrFj_eltX8CQMzDx47zH8CLmmkFEAcdvXYcgYAM1AMXFClhQKkVKqxOl88zwVgqoFuRiGdwAoOIVzsqCUM1WAWpKXXY1J6PaYdFWC7dfYYOJbd7DRd21Stm5StTf-R05jxx5Dg7EOvk1q7MvYxe7TWx_HS3JWlfsBr373irw93O82T-n29fF5c7dNLQcRU1OtVcnFGpnBqgDHGeNcMjCi4lYaIcGyknGzznPDJXAnFZPSOA6U5hUV-Ypkx14bumEIWOk--KYMo6agZyh6hqJnKHqGMgVujoH-YBp0f_ZfCpNBHQ04vf3hMejBemwtOh_QRu06_1_3NwpXcRk</recordid><startdate>20010701</startdate><enddate>20010701</enddate><creator>El-tawil, Osama S.</creator><creator>Abdel-rahman, Mohamed S.</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20010701</creationdate><title>The role of enzyme induction and inhibition on cypermethrin hepatotoxicity</title><author>El-tawil, Osama S. ; Abdel-rahman, Mohamed S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c406t-bf58a465e2bef90d42244720b6f4c7b670c2a24b533b4704d78277bd40113f163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Alanine Transaminase - drug effects</topic><topic>Alanine Transaminase - metabolism</topic><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Aspartate Aminotransferases - drug effects</topic><topic>Aspartate Aminotransferases - metabolism</topic><topic>Cell Survival - drug effects</topic><topic>Cells, Cultured</topic><topic>cypermethrin mechanism of action, synthetic pyrethroids, hepatotoxicity</topic><topic>Enzyme Activators - pharmacology</topic><topic>Enzyme Induction - drug effects</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Hepatocytes - drug effects</topic><topic>Hepatocytes - enzymology</topic><topic>Hepatocytes - metabolism</topic><topic>Insecticides - metabolism</topic><topic>Insecticides - toxicity</topic><topic>Male</topic><topic>Phenobarbital - pharmacology</topic><topic>Proadifen - pharmacology</topic><topic>Pyrethrins - metabolism</topic><topic>Pyrethrins - toxicity</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>El-tawil, Osama S.</creatorcontrib><creatorcontrib>Abdel-rahman, Mohamed S.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Pharmacological research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>El-tawil, Osama S.</au><au>Abdel-rahman, Mohamed S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The role of enzyme induction and inhibition on cypermethrin hepatotoxicity</atitle><jtitle>Pharmacological research</jtitle><addtitle>Pharmacol Res</addtitle><date>2001-07-01</date><risdate>2001</risdate><volume>44</volume><issue>1</issue><spage>33</spage><epage>39</epage><pages>33-39</pages><issn>1043-6618</issn><eissn>1096-1186</eissn><abstract>Cypermethrin at different concentrations (100, 200, 400 and 800 ng ml−1) was incubated with a primary culture of rat hepatocytes. Cypermethrin was cytotoxic to rat hepatocytes at concentrations of 200 ng ml−1or greater. Toxicity was measured by a decrease in cell viability and leakage of ALT and AST enzymes into the culture medium. The role of cytochrome P450 in the hepatotoxicity of cypermethrin insecticide was investigated in fresh hepatocytes isolated either from phenobarbital pretreated rats or control rats and coincubated with SKF525A. Pretreatment with phenobarbital strongly protected the hepatocytes against the cypermethrin induced loss of cell viability percentage and increased enzyme leakage percentage. Coincubation of the hepatocytes with SKF525A, a well-known cytochrome P450 inhibitor, substantially potentiated the effect of cypermethrin on cell viability and enzyme leakage. These results suggest that the cytocidal hepatotoxicity of cypermethrin in primary hepatocyte culture depends on its parent compound and phenobarbital, as a cytochrome P450 inducer, could be of therapeutic value.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>11428908</pmid><doi>10.1006/phrs.2001.0826</doi><tpages>7</tpages></addata></record> |
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| ispartof | Pharmacological research, 2001-07, Vol.44 (1), p.33-39 |
| issn | 1043-6618 1096-1186 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Alanine Transaminase - drug effects Alanine Transaminase - metabolism Analysis of Variance Animals Aspartate Aminotransferases - drug effects Aspartate Aminotransferases - metabolism Cell Survival - drug effects Cells, Cultured cypermethrin mechanism of action, synthetic pyrethroids, hepatotoxicity Enzyme Activators - pharmacology Enzyme Induction - drug effects Enzyme Inhibitors - pharmacology Hepatocytes - drug effects Hepatocytes - enzymology Hepatocytes - metabolism Insecticides - metabolism Insecticides - toxicity Male Phenobarbital - pharmacology Proadifen - pharmacology Pyrethrins - metabolism Pyrethrins - toxicity Rats Rats, Sprague-Dawley |
| title | The role of enzyme induction and inhibition on cypermethrin hepatotoxicity |
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