Antifibrogenic effect in vivo of low doses of insulin-like growth factor-I in cirrhotic rats.
Insulin-like growth factor-I (IGF-I) is produced mainly in the liver and it induces beneficial effects on the nutritional status, the liver function and oxidative hepatic damage in cirrhotic rats. The aim of this work was to analyze the effect of IGF-I on mechanisms of fibrogenesis in cirrhotic rats. Liver cirrhosis was induced by CCl(4) inhalation and phenobarbital in Wistar rats. Ten days after stopping CCl(4) administration (day 0), rats received either IGF-I (2 microg/100 g bw/day) (CI+IGF) or saline (CI) subcutaneously during 14 days. Animals were sacrificed on day 15. As control groups were used: healthy rats (CO) and healthy rats treated with IGF-I (CO+IGF). Liver histopathology, hydroxyproline content, prolyl hydroxylase activity, collagen I and III mRNA expression and the evolution of transformed Ito cells into myofibroblasts were assessed. Among the two control groups (CO+IGF), no differences were found in hydroxyproline content and these levels were lower than those found in the two cirrhotic groups. Compared with untreated cirrhotic rats, the CI+IGF-I animals showed a significant reduction in hydroxyproline content, prolyl hydroxylase activity and collagen alpha 1(I) and alpha1(III) mRNA expression. A higher number of transformed Ito cells (alpha-actin +) was observed in untreated cirrhotic animals as compared to CO and CI+IGF groups. In summary, treatment with IGF-I reduced all of the studied parameters of fibrogenesis. In conclusion, low doses of IGF-I induce in vivo an antifibrogenic effect in cirrhotic rats.
Muguerza
B
B
Department of Physiology, School of Medicine and Liver Unit, University of Navarra, Pamplona, Spain.
Castilla-Cortázar
I
I
García
M
M
Quiroga
J
J
Santidrián
S
S
Prieto
J
J
D000199:Actins / Q000032:analysis; D000818:Animals; D002251:Carbon Tetrachloride; D003094:Collagen / Q000032:analysis / Q000235:genetics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005355:Fibrosis / Q000517:prevention & control*; D006909:Hydroxyproline / Q000032:analysis; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D015227:Lipid Peroxidation; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D011393:Procollagen-Proline Dioxygenase / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D000199:Actins; D012333:RNA, Messenger; D008315:Malondialdehyde; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D002251:Carbon Tetrachloride; D011393:Procollagen-Proline Dioxygenase; D006909:Hydroxyproline