DC Field | Value | Language |
---|---|---|
dc.contributor.author | Jeong T. C. | ko |
dc.contributor.author | Matulka R. A. | ko |
dc.contributor.author | Jordan S. D. | ko |
dc.contributor.author | Holsapple M. P. | ko |
dc.contributor.author | Yang, Kyu Hwan | ko |
dc.date.accessioned | 2013-02-28T03:16:20Z | - |
dc.date.available | 2013-02-28T03:16:20Z | - |
dc.date.created | 2012-02-06 | - |
dc.date.created | 2012-02-06 | - |
dc.date.issued | 1995 | - |
dc.identifier.citation | IMMUNOPHARMACOLOGY, v.29, no.1, pp.37 - 46 | - |
dc.identifier.issn | 0162-3109 | - |
dc.identifier.uri | http://hdl.handle.net/10203/72480 | - |
dc.description.abstract | Cocaine has been reported to directly suppress the in vitro immune responses at very high concentrations. In the present study, the possible role of metabolism in cocaine-induced immunosuppression was investigated in splenocyte cultures isolated from B6C3F1 female mice. Since cocaine can be metabolized by both esterase and P-450 monooxygenase, we studied the direct effects of cocaine, benzoylecgonine and norcocaine on the in vitro T-dependent antibody response to SRBC. Direct exposure to cocaine only produced a modest (30%) but nonsignificant suppression of the antibody response, while benzoylecgonine, a primary product of metabolism by the esterase pathway, was devoid of activity. In contrast, direct exposure to norcocaine, the initial product of N-demethylation by the P-450 pathway, produced significant suppression at concentrations greater than or equal to 10 mu M. Similar results were observed in studies measuring LPS and Con A mitogenicity. Furthermore, a significant suppression was observed when splenocytes were preincubated for 1 h with 1 mM cocaine in the presence of liver S-9 fractions isolated from phenobarbital-induced mice. Meanwhile, no suppression was obtained when splenocytes were preincubated in the presence of untreated S-9 fractions. To characterize the mechanism of our results, the capacity of both untreated and phenobarbital-induced microsomes to produce formaldehyde from cocaine was compared. The N-demethylation of cocaine was NADPH-dependent and phenobarbital-induced microsomes produced approx, 6-times higher amounts of formaldehyde, indicating a greater portion of cocaine could be metabolized through the P-450 pathway to its toxic metabolites. Finally, because benzoylecgonine shares with cocaine the presence of a methyl group on the tropane nitrogen, we also compared the ability of N-demethylation from cocaine and benzoylecgonine in mouse liver microsomes. Our results indicated that benzoylecgonine could not be demethylated as determined by a failure to generate any formaldehyde. These results offer further support that the N-demethylation pathway is a critical step to cause its immunotoxicity. | - |
dc.language | English | - |
dc.publisher | ELSEVIER SCIENCE BV | - |
dc.subject | INDUCED HEPATIC-NECROSIS | - |
dc.subject | INDUCED HEPATOTOXICITY | - |
dc.subject | RAT HEPATOCYTES | - |
dc.subject | MIXED CULTURES | - |
dc.subject | HUMAN LIVER | - |
dc.subject | ETHANOL | - |
dc.subject | NORCOCAINE | - |
dc.subject | MOUSE | - |
dc.subject | DIMETHYLNITROSAMINE | - |
dc.subject | POTENTIATION | - |
dc.title | ROLE OF METABOLISM IN COCAINE-INDUCED IMMUNOSUPPRESSION IN SPLENOCYTE CULTURES FROM B6C3F1 FEMALE MICE | - |
dc.type | Article | - |
dc.identifier.wosid | A1995QH52200005 | - |
dc.identifier.scopusid | 2-s2.0-0028893985 | - |
dc.type.rims | ART | - |
dc.citation.volume | 29 | - |
dc.citation.issue | 1 | - |
dc.citation.beginningpage | 37 | - |
dc.citation.endingpage | 46 | - |
dc.citation.publicationname | IMMUNOPHARMACOLOGY | - |
dc.identifier.doi | 10.1016/0162-3109(95)00042-R | - |
dc.contributor.nonIdAuthor | Jeong T. C. | - |
dc.contributor.nonIdAuthor | Matulka R. A. | - |
dc.contributor.nonIdAuthor | Jordan S. D. | - |
dc.contributor.nonIdAuthor | Holsapple M. P. | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | COCAINE | - |
dc.subject.keywordAuthor | ANTIBODY RESPONSE | - |
dc.subject.keywordAuthor | N-DEMETHYLATION | - |
dc.subject.keywordAuthor | DRUG METABOLISM | - |
dc.subject.keywordPlus | INDUCED HEPATIC-NECROSIS | - |
dc.subject.keywordPlus | INDUCED HEPATOTOXICITY | - |
dc.subject.keywordPlus | RAT HEPATOCYTES | - |
dc.subject.keywordPlus | MIXED CULTURES | - |
dc.subject.keywordPlus | HUMAN LIVER | - |
dc.subject.keywordPlus | ETHANOL | - |
dc.subject.keywordPlus | NORCOCAINE | - |
dc.subject.keywordPlus | MOUSE | - |
dc.subject.keywordPlus | DIMETHYLNITROSAMINE | - |
dc.subject.keywordPlus | POTENTIATION | - |
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