Hepatoprotective effects of insulin-like growth factor I in rats with carbon tetrachloride-induced cirrhosis.
OBJECTIVE
Bioavailability of insulin-like growth factor (IGF-I) is reduced in liver cirrhosis. The aim of this study was to analyze the effect of IGF-I on liver histopathology and function in experimental cirrhosis.


METHODS
Rats received CCl4 inhalations for 11 or 30 weeks (protocols 1 and 2, respectively) and were treated with 2 microg x 100 g body wt(-1) x day(-1) IGF-I (group CI + IGF) or saline (group CI) on weeks 13 and 14 (protocol 1) or on weeks 28-30 (protocol 2). Normal rats were studied in parallel.


RESULTS
Serum albumin and total protein levels were reduced in CI but not in CI + IGF rats compared with normal rats. Clotting factors II, VII, and X were significantly greater in CI + IGF than in CI rats. Liver lipid peroxidation products were significantly increased in CI but not in CI + IGF rats, and liver fibrosis was less pronounced in CI + IGF than in CI animals. The activities of antioxidant enzymes and mitochondrial transmembrane potential were reduced compared with normal animals in CI but not in CI + IGF rats.


CONCLUSIONS
IGF-I improves liver function and reduces oxidative liver damage and fibrosis in rats with compensated or advanced liver cirrhosis. Improved mitochondrial function could play a role in the hepatoprotective effect of this hormone.
Castilla-Cortazar
I
I
Department of Human Physiology, School of Medicine, and University Clinic, University of Navarra, Pamplona, Spain.
Garcia
M
M
Muguerza
B
B
Quiroga
J
J
Perez
R
R
Santidrian
S
S
Prieto
J
J
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D003094:Collagen / Q000032:analysis; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D015227:Lipid Peroxidation; D008099:Liver / Q000473:pathology / Q000503:physiopathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008564:Membrane Potentials; D008928:Mitochondria / Q000737:chemistry / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000627:therapeutic use
D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D002251:Carbon Tetrachloride; D002374:Catalase