Hydrogen-rich saline protects against mitochondrial dysfunction and apoptosis in mice with obstructive jaundice

Abstract

Previous studies have demonstrated that hydrogen-rich saline (HS) protects against bile duct ligation (BDL)-induced liver injury by suppressing oxidative stress and inflammation. Mitochondria, which are targets of excessive reactive oxygen species and central mediators of apoptosis, have a pivotal role in hepatic injury during obstructive jaundice (OJ); however, the implications of HS in the hepatic mitochondria of BDL mice remain unknown. The present study investigated the hypothesis that HS could reduce OJ-induced liver injury through the protection of mitochondrial structure and function, as well as inhibition of the mitochondrial apoptotic pathway. Male C57BL/6 mice were randomly divided into three experimental groups: Sham operation group, BDL injury with normal saline (NS) treatment group, and BDL-injury with HS treatment group. Mitochondrial damage and apoptotic parameters were determined 3 days post-BDL injury and treatment. The results demonstrated that mitochondria isolated from the livers of NS-treated BDL mice exhibited increased mitochondrial swelling, cytochrome c release, and oxidative damage. In addition, liver samples from NS-treated BDL mice exhibited significant increases in B-cell lymphoma 2 (Bcl-2)-associated X protein expression, caspase activities, and hepatocyte apoptosis compared with livers from sham-operated controls. Notably, treatment with HS reduced the levels of these markers and alleviated morphological defects in the mitochondria following injury. In addition, HS markedly increased the antioxidant potential of mitochondria, as evidenced by elevated adenosine triphosphate levels, mitochondrial respiratory function, and increased levels of active Bcl-2. In conclusion, HS attenuates mitochondrial oxidative stress and dysfunction, and inhibits mitochondrial-mediated apoptosis in the livers of BDL mice.