Abstract:
:The cytotoxicity of paracetamol and of its putative toxic metabolite, N-acetyl-p-benzo-quinoneimine (NABQI) have been investigated in hepatocytes from hamster, mouse, rat and human liver. Whereas paracetamol readily caused cell blebbing and a loss of viability in hepatocytes from mouse and hamster, human and rat hepatocytes were much more resistant to these effects. In marked contrast, there were no significant differences in the sensitivity of the cells from any species to the toxic effects of NABQI. Glutathione depletion by NABQI and paracetamol correlated very well with the toxic effects of these compounds. It is concluded that species differences in sensitivity to the hepatotoxicity of paracetamol are due almost entirely to differences in the rate of formation of NABQI, and not to any intrinsic differences in sensitivity or in any difference in the fate of NABQI once formed. Further, man appears to be relatively resistant to the hepatotoxic effects of paracetamol, and the results in hepatocytes were confirmed by both in vitro and in vivo analyses.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Tee LB,Davies DS,Seddon CE,Boobis ARdoi
10.1016/0006-2952(87)90412-6subject
Has Abstractpub_date
1987-04-01 00:00:00pages
1041-52issue
7eissn
0006-2952issn
1873-2968pii
0006-2952(87)90412-6journal_volume
36pub_type
杂志文章abstract::We have investigated a series of novel 4-aminoquinoline analogues related to amodiaquine, that possess side chain modifications designed to influence both drug pKa and lipophilicity. These compounds have been used to determine the influence of physicochemical properties on antimalarial activity against, and accumulati...
journal_title:Biochemical pharmacology
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journal_title:Biochemical pharmacology
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journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
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journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2006.07.002
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2018.06.018
更新日期:2018-09-01 00:00:00
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pub_type: 杂志文章
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更新日期:2009-02-01 00:00:00
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journal_title:Biochemical pharmacology
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doi:10.1016/0006-2952(84)90581-1
更新日期:1984-07-01 00:00:00
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pub_type: 杂志文章,评审
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journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2018.04.026
更新日期:2018-08-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2008.02.005
更新日期:2008-05-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2020.114353
更新日期:2020-12-02 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(97)00265-7
更新日期:1998-02-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2004.07.042
更新日期:2004-12-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90644-7
更新日期:1987-10-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2012.06.014
更新日期:2012-09-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(02)01139-5
更新日期:2002-09-01 00:00:00
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pub_type: 杂志文章
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更新日期:1989-05-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2008.08.026
更新日期:2008-12-01 00:00:00
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更新日期:2018-09-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
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更新日期:2011-10-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
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更新日期:1982-12-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2007.08.029
更新日期:2008-01-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2008.11.029
更新日期:2009-03-15 00:00:00
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pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2020.114360
更新日期:2021-01-01 00:00:00
abstract::The binding of 1,1-dichloroethane (1,1-DCE) to the substrate binding site of hepatic microsomal cytochrome P-450, and the stimulation of hepatic microsomal CO-inhibitable NADPH oxidation by 1,1-DCE and 1,2-dichloroethane (1,2-DCE) were enhanced by induction with phenobarbital but not with beta-naphthoflavone. Incubati...
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pub_type: 杂志文章
doi:10.1016/0006-2952(83)90545-2
更新日期:1983-01-15 00:00:00
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pub_type: 杂志文章
doi:10.1016/0006-2952(93)90382-7
更新日期:1993-01-07 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2004.10.012
更新日期:2005-02-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)02061-6
更新日期:1995-10-26 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(96)00819-2
更新日期:1997-03-21 00:00:00