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Introduction
Obstructive jaundice (OJ) occurs due to occlusion of the common bile duct, or complications associated with surgery, tumor, trauma, gallstones, hepatitis, or idiopathic and metabolic diseases, including primary biliary cirrhosis and sclerosing cholangitis (1). Cholestatic liver injury is accompanied by serious complications, which increase the risk of mortality and morbidity (2). The mechanisms by which cholestasis induce acute liver injury remain controversial; however, intrahepatic accumulation of reactive oxygen species (ROS) is thought to be an important contributory factor (3–5). ROS are able to trigger the opening of mitochondrial permeability transition (MPT) pores in the mitochondrial inner membrane, which nonspecifically transport solutes up to a molecular mass of 1,500 Da (6). Opening of MPT pores lead to cytochrome c release and apoptosis (7,8). Previous studies have indicated that mitochondrial stress and apoptosis have an important role in hepatic injury in OJ (8,9). In particular, it has been demonstrated that, following cholestasis, an accumulation of bile acids in hepatocytes contributes to cell death and is one of the major pathogenic factors resulting in chronic liver damage and fibrosis (10).
Hydrogen (H2), in the gaseous state or dissolved in water, has been reported to have therapeutic value as a selective antioxidant via its ability to reduce cytotoxic ROS and to suppress inflammatory reactions (11–13). Unlike other gaseous molecules, H2 can penetrate the cell membrane to reach subcellular compartments, including mitochondria, which are notoriously difficult to target. The utilization of H2 gas-saturated physiological saline, also known as hydrogen-rich saline (HS), is considered to be less complicated and safer than H2 gas inhalation for clinical application. Furthermore, we have previously demonstrated that HS is able to attenuate bile duct ligation (BDL)-induced liver damage by reducing hepatic oxidative stress and inflammation, and can reduce apoptosis in neonatal brain tissue from a rat model of hypoxia-ischemia (14,15). The present study specifically assessed the impact of BDL-induced injury on the hepatic mitochondria of mice, in order to investigate whether HS was able to exert direct protective effects on the mitochondria, and thus prevent mitochondrial damage and mitochondria-induced hepatocyte apoptosis.
Materials and methods
HS production
HS was prepared as previously described (16). HS was freshly prepared on a weekly basis to ensure that a concentration >0.6 mmol/l was...