Mitochondrial protection by low doses of insulin-like growth factor-Iin experimental cirrhosis

Figure 1 Histopathological comparative study (4 &mgr;m sections; Masson’s trichrome stain). An evident reduction of fibrosis was found in the cirrhotic group treated with IGF-I in agreement with previous studies[121415].

Figure 2 Mitochondrial Membrane Potential (MMP): the MMP was evaluated by flow cytometry with Rhodamine 123 under respiratory conditions (with succinate), state 4 (A) and with ADP state 3 (B). MMP is expressed as fluorescence arbitrary units (FAU). mean ± SEM; ^aP < 0.05, ^bP < 0.01.

Figure 3 Intramitochondrial ROS production in isolated mitochondria: mitochondria from untreated cirrhotic rats showed an increased production of free radicals as compared to healthy controls (CO) and cirrhotic rats treated with IGF-I (CI + IGF). mean ± SEM; ^aP < 0.05.

Figure 4 Complex V ATPase activity: ATPase activity was significantly reduced in mitochondria from untreated cirrhotic rats (P < 0. 05 vs CO group). IGF-therapy induced a little increase of ATPase activity (P = no significant vs CO group). mean ± SEM; ^aP < 0.05.

Figure 5 Active fragment of caspase 3 by Western blot in liver homogenates: untreated cirrhotic rats showed an increment of caspase activation. IGF-I replacement therapy induced an inhibition of caspase 3 activation. ^bP < 0.01; ^dP < 0.001.

Figure 6 Apoptosis by TUNEL in the liver from the three experimental groups: the number of TUNEL positive hepatocytes was increased in untreated cirrhotic rats (CI) as compared to healthy controls (CO). IGF-Itherapy reduced signifincantly apoptosis in hepatocytes.