Carbon tetrachloride-induced hepatotoxicity in pregnant and lactating rats
| Autor: | Yoshito Nishihata, Yoshinaka Urasoko, Takashi Kamata, Satomi Shimizu, Hiroshi Edamoto, Masahiro Mochizuki, Takahiro Kitazawa, Takumi Ohishi, Daichi Nakamura, Kazuhiko Umeshita |
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| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty Blotting Western CCL4 Toxicology digestive system chemistry.chemical_compound Necrosis Pregnancy Lactation Internal medicine Lactate dehydrogenase parasitic diseases medicine Animals Carbon Tetrachloride Chemistry Carbon Tetrachloride Poisoning Cytochrome P-450 CYP2E1 CYP2E1 medicine.disease digestive system diseases Animals Suckling Rats Disease Models Animal medicine.anatomical_structure Endocrinology Blood chemistry Vacuoles Carbon tetrachloride Hepatocytes Microsomes Liver Gestation Female Chemical and Drug Induced Liver Injury Blood Chemical Analysis |
| Zdroj: | The Journal of toxicological sciences. 34(2) |
| ISSN: | 1880-3989 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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