Abstract:
:We have previously reported that rats are resilient to the hepatotoxic and lethal combination of chlordecone (CD) and carbon tetrachloride (CCl4) during early postnatal development. The overall findings pointed to stimulated cell division and tissue repair mechanisms as the underlying cause of resistance. The objective of the current study was to investigate if the antimitotic effect of colchicine (CLC) abolishes this resiliency to CD + CCl4 by inhibiting ongoing and stimulated cell division. We used 45-day-old rats in this study because this age group exhibited partial sensitivity to CD + CCl4 in our previous studies. Male Sprague-Dawley rats were treated with a single low intraperitoneal dose of CCl4 (100 microl/kg) or corn oil after exposure to either 10 ppm CD in the diet or a normal diet (ND) for 15 days. CLC (1 mg/kg) was administered 6 or 30 hr after CCl4 to ND or CD rats, respectively. Administration of CLC resulted in increased CCl4-induced mortality from 25% to 85% in rats pretreated with CD, in contrast to 100% survival in ND rats. Liver injury was assessed by plasma alanine transaminase (ALT) and sorbitol dehydrogenase (SDH) elevations as well as by histopathology. Hepatocellular regeneration was assessed by 3H-thymidine (3H-T) incorporation into hepatonuclear DNA and proliferating cell nuclear antigen (PCNA) studies during 0-96 hr after CCl4. Administration of CLC to ND + CCl4 rats resulted in a slight delay in cell division and tissue repair, as indicated by 3H-T incorporation and PCNA, thereby leading to prolonged liver injury as revealed by elevations in plasma ALT, SDH, and histopathological lesions. In contrast, CLC administration to CD + CCl4-treated rats further delayed and diminished cell division by 80%, which led to unrestrained progression of CCl4-induced liver injury, resulting in 85% mortality. These findings underscore the importance of ongoing and toxicant-stimulated cell division and tissue repair mechanisms in hepatotoxicity, and the need for the inclusion of age factors in risk assessment of exposure to environmental and other chemicals.
journal_name
Environ Health Perspectjournal_title
Environmental health perspectivesauthors
Dalu A,Rao PS,Mehendale HMdoi
10.1289/ehp.98106597subject
Has Abstractpub_date
1998-09-01 00:00:00pages
597-606issue
9eissn
0091-6765issn
1552-9924journal_volume
106pub_type
杂志文章abstract:BACKGROUND:Psychological sequelae are among the most pronounced effects in populations following exposure to oil spills. Women in particular represent a vulnerable yet influential population but have remained relatively understudied with respect to the Deepwater Horizon oil spill (DHOS). OBJECTIVE:To describe the rela...
journal_title:Environmental health perspectives
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更新日期:2016-09-01 00:00:00
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更新日期:2021-01-01 00:00:00
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更新日期:2001-10-01 00:00:00
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更新日期:2002-03-01 00:00:00
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更新日期:2013-06-01 00:00:00
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更新日期:1998-10-01 00:00:00
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