Carbon tetrachloride-induced acute liver injury in Mini and Wistar rats.
Acute liver injury induced by CCl4 injection (0.5 ml/kg b.w.) was compared between Mini and Wistar rats. Mini rats (Jcl:Wistar-TgN (ARGHGEN)1Nts strain) are Wistar-derived transgenic animals in which the expression of growth hormone (GH) gene is suppressed by the presence of an antisense transgene. The hepatic lesion appeared earlier and its recovery was delayed in Mini rats compared to in Wistar rats. The degree of the liver injury was more severe in Mini rats than in Wistar rats, and this corresponded well with the changes in serum AST level. Moreover, in accordance with the localization of CYP2E1-positive hepatocytes in the early stage after CCl4 treatment, the initial lesion characterized by ballooning of hepatocytes developed in the centrilobular zone in Wistar rats while it appeared in the middle zone in Mini rats. The changes in the percentage of PCNA-positive cells and the levels of HGF and TGF-beta1 mRNAs were clearly different between the two strains. These results indicate that the response of the liver to CCl4 is different between GH-suppressed Mini rats and Wistar rats.
Shimizu
H
H
Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan.
Uetsuka
K
K
Nakayama
H
H
Doi
K
K
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000633:toxicity; D002252:Carbon Tetrachloride Poisoning / Q000097:blood / Q000473:pathology*; D002452:Cell Count; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000473:pathology*; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis / Q000235:genetics; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics
D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D017228:Hepatocyte Growth Factor; D002251:Carbon Tetrachloride; D019392:Cytochrome P-450 CYP2E1; D001219:Aspartate Aminotransferases; D000469:Alkaline Phosphatase