Hepatoprotective effects of insulin-like growth factor I in rats with carbon tetrachloride-induced cirrhosis.

BACKGROUND & AIMS 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.

[1]  J. Prieto,et al.  Low doses of insulin-like growth factor-I improve nitrogen retention and food efficiency in rats with early cirrhosis. , 1997, Journal of hepatology.

[2]  J. O'connor,et al.  Oxidative metabolism in a rat hepatoma (N13) and isolated rat hepatocytes: A flow cytometric comparative study , 1996, Hepatology.

[3]  R. Schlapbach,et al.  Oxidants in mitochondria: from physiology to diseases. , 1995, Biochimica et biophysica acta.

[4]  C. Lieber.  Alcohol and the liver: 1994 update. , 1994, Gastroenterology.

[5]  D. Clemmons,et al.  Clinical Uses of Insulin-like Growth Factor I , 1994, Annals of Internal Medicine.

[6]  J. McCord.  Human disease, free radicals, and the oxidant/antioxidant balance. , 1993, Clinical biochemistry.

[7]  E. D. Harris,et al.  Regulation of antioxidant enzymes 1 , 1992, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[8]  H. Imura,et al.  Serum growth hormone-binding protein, insulin-like growth factor-I, and growth hormone in patients with liver cirrhosis. , 1992, Metabolism: clinical and experimental.

[9]  W. Jiménez,et al.  Measurement of fibrosis in needle liver biopsies: Evaluation of a colorimetric method , 1985, Hepatology.

[10]  K. Chatamra,et al.  Phenobarbitone-induced enlargement of the liver in the rat: its relationship to carbon tetrachloride-induced cirrhosis. , 1981, British journal of experimental pathology.

[11]  R. Burk,et al.  Glutathione peroxidase activity in selenium-deficient rat liver. , 1976, Biochemical and biophysical research communications.

[12]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[13]  W. Crocker.  Catalase , 1911, Botanical Gazette.

[14]  G. Gores,et al.  Liver cell necrosis: cellular mechanisms and clinical implications. , 1995, Gastroenterology.

[15]  B. P. Yu,et al.  Cellular defenses against damage from reactive oxygen species. , 1994, Physiological reviews.

[16]  C. Lieber,et al.  Alcohol and the Liver , 1992 .

[17]  J. McCord,et al.  Mitochondrial generation of oxygen radicals during reoxygenation of ischemic tissues. , 1991, Free radical research communications.

[18]  Y. Murawaki,et al.  Increase in lipoperoxides and prolyl hydroxylase activity in rat liver following chronic ethanol feeding. , 1990, Biochemical Pharmacology.

[19]  P. Dagnelie,et al.  Disorders of nutrition and intermediary metabolism , 1988 .