Carbontetrachloride - induced hepatotoxicity in and lactating rats pregnant

Carbon tetrachloride (CCI,) is well known to indnce hepatotoxicity after being metabolized to trichloromcthyl frec radical (・CCI,) by CYP2El . In the prcsent study, the hepatotoxicity induccd by a single oral dose (2,OOO mg/kg) of CCI, was compared bctween pregnant (gestation days (GD) I3 and 19) or postpartum (postpartum days (PPD) 1, 13 and 27) and non-pregnant rats. Hepatotoxicity in CCI,treated pregnant rats evaluated by blood chemistry (alanine aminotransferase (AVI]), 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-prcgpant rats. CYP2E1 expression in non-treatcd pregnant rats decreased as pregnancy progrcssed and reached minimum leyel on GD19. Thus, the degrce ot' CCI,-induced hepatotoxicity roughly corrcspondcd to CYP2E1 lcvels during pregnancy. Aftcr delivcry, hepatotexicity in CCI,-treated lactating rats was maximal on PPDI 3, being strongcr than that in non-pregnant rats, and then it decreased slightly on PPD27, Thc CYP2E1 levcl in the nontreated lactating rats tendcd to increasc but rcmained at lowcr levels until PPD13 compared with that in non-prcgnant rats. Thus, the dcgree of CCI,-induced hepatotoxicity d d not correspond to CYP2E1 levels during lactation. This suggests that during lactation, there may be certain factors othcr than CYP2El exprcssion responsible for the degree of CCI,-induced hepatotoxicity. Key vtords: Carbon tetrachloride, HepatotoxicitM Pregnancy, Lactation, CYP2E1, Rat