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

Abstract

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.