Acute liver CCl(4) intoxication causes low HSP70 gene expression and a delayed transition through the cell cycle in aged rats.
Since there is still debate about the ability of the aged liver to regenerate, we compared some aspects of this response in young, adult and old rodents. 2, 6, 12 and 19-month-old rats were intraperitoneally injected with CCl(4) (3mg/kg) or left untreated (CT) and killed either 2h (group A) or 24h (group B) after intoxication. Liver injury was checked histologically and by assaying transaminases. mRNA levels of albumin (Alb), c-fos, c-myc, hepatocyte growth factor (HGF), transforming growth factor (TGF)-alpha and TGF-beta1 were also analyzed. Heat shock protein (HSP)70 gene expression was evaluated, and liver GSH content. Transaminases and histology show more damage in aged rats. Alb mRNA was reduced starting at 12 months in group A and at all ages in group B; c-fos and c-myc mRNAs reached the highest levels in 6-month-old rats and the lowest in those aged 12 and 19 months of group A. In group B, c-fos was detectable only in 6-month animals, but c-myc at all ages. HGF, TGF-alpha and TGF-beta1 mRNAs were up-regulated in treated rats, but to a lesser extent in the aged. HSP70 mRNA, absent in CT, was significantly increased at the age of 6 months, undetectable in the oldest rats in group A; in group B it was only visible in 6-month animals. GSH content was reduced with aging. In conclusion, during aging the liver regenerative machinery is preserved but its activation is reduced and delayed.
Gagliano
Nicoletta
N
Cattedra di Geron. e Geriatria Dept. of Geriatrics, Ospedale Maggiore IRCCS, Via Pace 9, Milan, Italy.
Arosio
Beatrice
B
Grizzi
Fabio
F
Vergani
Carlo
C
Annoni
Giorgio
G
D000375:Aging / Q000378:metabolism*; D000410:Alanine Transaminase / Q000097:blood; D000418:Albumins / Q000235:genetics; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000008:administration & dosage / Q000494:pharmacology*; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D005978:Glutathione / Q000097:blood; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D017228:Hepatocyte Growth Factor / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D016211:Transforming Growth Factor alpha / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1
D000418:Albumins; D018840:HSP70 Heat-Shock Proteins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; C508962:Tgfb1 protein, rat; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017228:Hepatocyte Growth Factor; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione