Antioxidant effects of insulin-like growth factor-I (IGF-I) in rats with advanced liver cirrhosis.
BACKGROUND
The exogenous administration of Insulin-like Growth Factor-I (IGF-I) induces hepatoprotective and antifibrogenic actions in experimental liver cirrhosis. To better understand the possible pathways behind the beneficial effect of IGF-I, the aim of this work was to investigate severe parameters involved in oxidative damage in hepatic tissue from cirrhotic animals treated with IGF-I (2 microg x 100 g(-1) x day(-1)). Iron and copper play an important role in oxidative mechanisms, producing the deleterious hydroxyl radical (*OH) that peroxides lipid membranes and damages DNA. Myeloperoxidase (MPO) and nitric oxide (NO) are known sources of free radicals and induce reduction of ferritin-Fe3+ into free Fe2+, contributing to oxidative damage.


METHODS
Liver cirrhosis was induced by CCl4 inhalation in Wistar male rats for 30 weeks. Healthy controls were studied in parallel (n = 10). Fe and Cu were assessed by atomic absoption spectrometry and iron content was also evaluated by Perls' staining. MPO was measured by ELISA and transferrin and ferritin by immunoturbidimetry. iNOS expression was studied by immuno-histochemistry.


RESULTS
Liver cirrhosis was histologically proven and ascites was observed in all cirrhotic rats. Compared to controls untreated cirrhotic rats showed increased hepatic levels of iron, ferritin, transferrin (p < 0.01), copper, MPO and iNOS expression (p < 0.01). However, IGF-treatment induced a significant reduction of all these parameters (p < 0.05).


CONCLUSIONS
the hepatoprotective and antifibrogenic effects of IGF-I in cirrhosis are associated with a diminution of the hepatic contents of several factors all of them involved in oxidative damage.
García-Fernández
María
M
Department of Physiology, School of Medicine, University of Navarra, Pamplona, Spain. igf@uma.es <igf@uma.es>
Castilla-Cortázar
Inma
I
Díaz-Sanchez
Matías
M
Navarro
Iñigo
I
Puche
Juan Enrique
JE
Castilla
Alberto
A
Casares
Amelia Díaz
AD
Clavijo
Encarna
E
González-Barón
Salvador
S
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003300:Copper / Q000378:metabolism; D005293:Ferritins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism* / Q000473:pathology*; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D014168:Transferrin / Q000378:metabolism
D000975:Antioxidants; D014168:Transferrin; D008315:Malondialdehyde; D007334:Insulin-Like Growth Factor I; D003300:Copper; D005293:Ferritins; D007501:Iron
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