Abstract
Chemical injury is partly due to free radical lipid peroxidation, which can induce oxidative stress and produce a large number of reactive oxygen species (ROS). Oxaloacetic acid is an important intermediary in the tricarboxylic acid cycle (TCA cycle) and participates in metabolism and energy production. In our study, we found that oxaloacetate (OA) effectively alleviated liver injury which was induced by hydrogen peroxide (H2O2) in vitro and carbon tetrachloride (CCl4) in vivo. OA scavenged ROS, prevented oxidative damage and maintained the normal structure of mitochondria. We further confirmed that OA increased adenosine triphosphate (ATP) by promoting the TCA production cycle and oxidative phosphorylation (OXPHOS). Finally, OA inhibited the mitogen-activated protein kinase (MAPK) and apoptotic pathways by suppressing tumor necrosis factor-α (TNF-α). Our findings reveal a mechanism for OA ameliorating chemical liver injury and suggest a possible implementation for preventing the chemical liver injury.
Highlights
The liver is an important metabolic organ, and its injury can be caused by viral infiltration, drugs, or toxic chemicals via infection or ingestion [1,2,3]
Chemical injury is partly due to free radical lipid peroxidation [4], which can induce oxidative stress and produce a large number of reactive oxygen species (ROS) [5,6]
These results indicate that OA had protective effects on H2O2-induced injury on the liver cells
Summary
The liver is an important metabolic organ, and its injury can be caused by viral infiltration, drugs, or toxic chemicals via infection or ingestion [1,2,3]. Chemical injury is partly due to free radical lipid peroxidation [4], which can induce oxidative stress and produce a large number of reactive oxygen species (ROS) [5,6]. The increasing levels of ROS can lead to dysfunction of the mitochondrial electron transport chain and tricarboxylic acid cycle (TCA cycle). The resulting lack of an energy supply causes cell injury and even death. Activation of mitochondrial apoptotic pathway is an important cause of liver injury [8,9,10]
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