Document Detail

Carbon tetrachloride-induced hepatotoxicity in pregnant and lactating rats.
MedLine Citation:
PMID:  19336974     Owner:  NLM     Status:  MEDLINE    
Carbon tetrachloride (CCl4) is well known to induce hepatotoxicity after being metabolized to trichloromethyl free radical ((.)CCl3) by CYP2E1. In the present study, the hepatotoxicity induced by a single oral dose (2,000 mg/kg) of CCl4 was compared between pregnant (gestation days (GD) 13 and 19) or postpartum (postpartum days (PPD) 1, 13 and 27) and non-pregnant rats. Hepatotoxicity in CCl4-treated pregnant rats evaluated by blood chemistry (alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) activities) and histopathological finding (area of damaged hepatocytes) was minimal on GD19, being weaker than that in non-pregnant rats. CYP2E1 expression in non-treated pregnant rats decreased as pregnancy progressed and reached minimum level on GD19. Thus, the degree of CCl4-induced hepatotoxicity roughly corresponded to CYP2E1 levels during pregnancy. After delivery, hepatotoxicity in CCl4-treated lactating rats was maximal on PPD13, being stronger than that in non-pregnant rats, and then it decreased slightly on PPD27. The CYP2E1 level in the non-treated lactating rats tended to increase but remained at lower levels until PPD13 compared with that in non-pregnant rats. Thus, the degree of CCl4-induced hepatotoxicity did not correspond to CYP2E1 levels during lactation. This suggests that during lactation, there may be certain factors other than CYP2E1 expression responsible for the degree of CCl4-induced hepatotoxicity.
Masahiro Mochizuki; Satomi Shimizu; Yoshinaka Urasoko; Kazuhiko Umeshita; Takashi Kamata; Takahiro Kitazawa; Daichi Nakamura; Yoshito Nishihata; Takumi Ohishi; Hiroshi Edamoto
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of toxicological sciences     Volume:  34     ISSN:  1880-3989     ISO Abbreviation:  J Toxicol Sci     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-01     Completed Date:  2009-06-23     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7805798     Medline TA:  J Toxicol Sci     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  175-81     Citation Subset:  IM    
Toxicology Department, Gotemba Laboratory, Bozo Research Center Inc., Shizuoka.
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MeSH Terms
Animals, Suckling / blood
Blood Chemical Analysis
Blotting, Western
Carbon Tetrachloride / toxicity*
Carbon Tetrachloride Poisoning / blood,  pathology*
Cytochrome P-450 CYP2E1 / metabolism
Disease Models, Animal
Drug-Induced Liver Injury / blood,  etiology,  pathology*
Hepatocytes / drug effects,  metabolism,  pathology
Lactation / blood,  drug effects*
Microsomes, Liver / drug effects,  enzymology
Necrosis / chemically induced,  pathology
Vacuoles / drug effects,  pathology
Reg. No./Substance:
56-23-5/Carbon Tetrachloride; EC P-450 CYP2E1

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