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The aim of this study was to determine whether caffeine enhanced radiosensitivity of normal liver tissue in a rat radiation-induced liver disease model. Buffalo rat McA-RH7777 hepatocellular cancer cells and BRL3A normal liver cells were irradiated, and cell cycle distribution and apoptosis rates were analyzed. A rat model of radiation-induced liver disease was established, rats were randomized into four groups: control; caffeine alone; irradiation (IR) alone; and caffeine plus IR (Caff + IR) group. Apoptosis rates in normal rat liver tissue after IR were evaluated by TUNEL staining and caspase-3 Western blot. Transaminase activity was measured and histopathological examination was done after IR. Caffeine abrogated IR-induced G2 phase arrest (Caff + IR vs. IR: 40.9 ± 4.0 vs. 60.7 ± 5.5%, at 12 h after IR) and increased apoptosis rates (Caff + IR vs. IR: 56.1 ± 6.8 vs. 35.5 ± 4.0%, at 72 h after IR) in McA-RH7777 cells, but did not affect IR-induced G2 phase arrest and apoptosis rates at any time point after IR in BRL3A cells. Caffeine did not enhance apoptosis, transaminase activity, or histopathological injury of normal rat liver tissue at any time points after IR. This study suggests that caffeine might not enhance radiosensitivity of normal liver tissue in vivo. In an earlier study, we reported that caffeine enhanced radiosensitivity of human hepatocellular cancer in a nude mice model. Together, these results offer feasibility of clinical application.

Purpose: We determined whether anti-transforming growth factor-β (TGF-β) intervention could halt the progression of established radiation-induced liver fibrosis (RILF)., Methods and Materials: A replication-defective adenoviral vector expressing the extracellular portion of human TβRII and the Fc portion of immunoglobulin G fusion protein (AdTβRIIFc) was produced. The entire rat liver was exposed to 30 Gy irradiation to generate a RILF model (RILFM). Then, RILFM animals were treated with AdTβRIIFc (1 × 10(11) plaque-forming units [PFU] of TβRII), control virus (1 × 10(11) PFU of AdGFP), or saline. Delayed radiation liver injury was assessed by histology and immunohistochemistry. Chronic oxidative stress damage, hepatic stellate cell activation, and hepatocyte regeneration were also analyzed., Results: In rats infected with AdTβRIIFc, fibrosis was significantly improved compared with rats treated with AdGFP or saline, as assessed by histology, hydroxyproline content, and serum level of hyaluronic acid. Compared with AdGFP rats, AdTβRIIFc-treated rats exhibited decreased oxidative stress damage and hepatic stellate cell activation and preserved liver function., Conclusions: Our results demonstrate that TGF-β plays a critical role in the progression of liver fibrosis and suggest that anti-TGF-β intervention is feasible and ameliorates established liver fibrosis. In addition, chronic oxidative stress may be involved in the progression of RILF., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Purpose: To determine whether the inhibition of Kupffer cells before radiotherapy (RT) would protect hepatocytes from radiation-induced apoptosis., Materials and Methods: A single 30-Gy fraction was administered to the upper abdomen of Sprague-Dawley rats. The Kupffer cell inhibitor gadolinium chloride (GdCl3; 10 mg/kg body weight) was intravenously injected 24 h before RT. The rats were divided into four groups: group 1, sham RT plus saline (control group); group 2, sham RT plus GdCl3; group 3, RT plus saline; and group 4, RT plus GdCl3. Liver tissue was collected for measurement of apoptotic cytokine expression and evaluation of radiation-induced liver toxicity by analysis of liver enzyme activities, hepatocyte micronucleus formation, apoptosis, and histologic staining., Results: The expression of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha was significantly attenuated in group 4 compared with group 3 at 2, 6, 24, and 48 h after injection (p <0.05). At early points after RT, the rats in group 4 exhibited significantly lower levels of liver enzyme activity, apoptotic response, and hepatocyte micronucleus formation compared with those in group 3., Conclusion: Selective inactivation of Kupffer cells with GdCl3 reduced radiation-induced cytokine production and protected the liver against acute radiation-induced damage., (Copyright 2010 Elsevier Inc. All rights reserved.)

Purpose: To investigate the regenerative capacity and proliferation related to cell cycle modulators in irradiated livers after partial hepatectomy (PH) in rats., Methods and Materials: Two experimental groups were given a single dose of either 4-Gy or 8-Gy photon radiation to the whole liver following PH. The control group underwent only PH, without irradiation. The liver specimens were analysed for apoptosis, proliferation and cell cycle related genes between 0.5 and 12 days., Results: Mean change in weight of the remnant liver in the 8-Gy group was significantly lower than in the control and 4-Gy groups. The apex of proliferating cell nuclear antigen labelling and bromodeoxyuridine incorporation index in two irradiated groups were also apparently lower than that in control group. After PH, transforming growth factor beta-1 (TGFbeta1), and the type II receptor of TGFbeta (TGFbetaR-II), anti-tumour protein 53(p53) and anti-tumour protein21(p21) protein expression in the irradiated livers was higher than in unirradiated ones. Significant apoptosis was noted in 8-Gy group. However, the maximal value of hepatocyte growth factor (HGF) mRNA and protein expression in the irradiated group was suppressed and restoration of liver function was delayed., Conclusion: Whole liver lower dose irradiation can attenuate regenerative capacity following partial hepatectomy in rats.