The influence of sorafenib on hepatic encephalopathy and the mechanistic survey in cirrhotic rats
Journal
European Journal of Clinical Investigation
Journal Volume
42
Journal Issue
12
Pages
1309-1316
Date Issued
2012
Author(s)
Abstract
Background Sorafenib, a multikinase inhibitor that inhibits angiogenesis and carcinogenesis, has been used for patients with advanced hepatocellular carcinoma. However, sporadic cases have been reported with the development of hepatic encephalopathy (HE) after sorafenib treatment, mostly in those with cirrhosis. Liver function impairment, portal-systemic collaterals and brain oxidative stress participate in the pathogenesis of HE. The study therefore aimed to investigate the potential influences of sorafenib on HE and the relevant risk factors in cirrhotic rats. Methods Liver cirrhosis was induced in Spraque-Dawley rats with common bile duct ligation (CBDL). CBDL rats received sorafenib 1mg/kg/day or distilled water (DW) via oral gavage since the 15th day post surgery for 2weeks. On the 28th day, after motor activities measurements, mean arterial pressure, portal pressure and heart rate were checked. Thereafter, cerebral cortex and cerebellum were dissected for oxidative stress study and blood was collected for liver biochemistry survey. Results Sorafenib significantly reduced portal pressure (22%) and collateral shunting degree (15%) in cirrhotic rats. Alanine transaminase, aspartate transaminase, total bilirubin and ammonia were similar in sorafenib- and DW-treated groups. Motor activities were not significantly altered by sorafenib. In cerebrum, the oxidant and antioxidant substances activities were not significantly different between the two groups, whereas they were divergent in cerebellum and hippocampus. Conclusion By surveying three main aspects involved in the pathogenesis of HE, this study demonstrates that sorafenib does not increase the risk of HE in cirrhotic rats. ? 2012 Stichting European Society for Clinical Investigation Journal Foundation.
Subjects
Hepatic encephalopathy; Liver cirrhosis; Oxidative stress; Portal hypertension; Sorafenib
SDGs
Other Subjects
alanine aminotransferase; ammonia; aspartate aminotransferase; bilirubin; glutathione; malonaldehyde; sorafenib; superoxide dismutase; animal experiment; animal model; animal tissue; antioxidant activity; article; bile duct ligation; body weight; brain cortex; brain tissue; cerebellum; controlled study; heart rate; hemodynamics; hepatic encephalopathy; histopathology; liver cirrhosis; male; mean arterial pressure; motor activity; nonhuman; oxidative stress; portal vein blood pressure; priority journal; rat; risk factor; Animals; Disease Models, Animal; Hepatic Encephalopathy; Humans; Hypertension, Portal; Liver Cirrhosis, Experimental; Male; Niacinamide; Oxidative Stress; Phenylurea Compounds; Protein Kinase Inhibitors; Rats; Rats, Sprague-Dawley
Type
journal article