Astaxanthin Pretreatment Attenuates Hepatic Ischemia Reperfusion-Induced Apoptosis and Autophagy via the ROS/MAPK Pathway in Mice

Abstract

Background: Hepatic ischemia reperfusion (IR) is an important issue in complex liver resection and liver transplantation. The aim of the present study was to determine the protective effect of astaxanthin (ASX), an antioxidant, on hepatic IR injury via the reactive oxygen species/mitogen-activated protein kinase (ROS/MAPK) pathway. Methods: Mice were randomized into a sham, IR, ASX or IR + ASX group. The mice received ASX at different doses (30 mg/kg or 60 mg/kg) for 14 days. Serum and tissue samples at 2 h, 8 h and 24 h after abdominal surgery were collected to assess alanine aminotransferase (ALT), aspartate aminotransferase (AST), inflammation factors, ROS, and key proteins in the MAPK family. Results: ASX reduced the release of ROS and cytokines leading to inhibition of apoptosis and autophagy via down-regulation of the activated phosphorylation of related proteins in the MAPK family, such as P38 MAPK, JNK and ERK in this model of hepatic IR injury. Conclusion: Apoptosis and autophagy caused by hepatic IR injury were inhibited by ASX following a reduction in the release of ROS and inflammatory cytokines, and the relationship between the two may be associated with the inactivation of the MAPK family.

Prophylactic Treatment with Cerium Oxide Nanoparticles Attenuate Hepatic Ischemia Reperfusion Injury in Sprague Dawley Rats

“…Current treatment strategies to attenuate IR induced injury is largely supportive in nature and fails to improve graft/hepatic function. Recent studies have suggested that IR injury is primarily mediated by excess ROS formation and subsequent activation of Kupffer cells that drive the inflammatory cascade [1]. So far, studies employing the use of anti-oxidants for the treatment of hepatic IR demonstrated promising results in animal models but failed to translate the same for clinical applications [29].…”

“…Hepatic ischemia reperfusion (IR) injury is a serious complication associated with liver transplantation and graft failure [1]. IR injury is a biphasic phenomenon that involves a temporary shut off in blood supply to the whole or part of a liver followed by sudden reperfusion [2].…”

Salidroside pretreatment attenuates apoptosis and autophagy during hepatic ischemia–reperfusion injury by inhibiting the mitogen-activated protein kinase pathway in mice

“…After the release of ROS, a cascade of mediators are activated, which injure different cells, including hepatocytes and endothelial cells 3–6. Inflammatory reactions and inflammatory cytokines are key factors in hepatic IRI.…”

The protective effects of shikonin on hepatic ischemia/reperfusion injury are mediated by the activation of the PI3K/Akt pathway

“…The regulation of autophagy involves various genes, including Beclin-1, LC3, and P6226272829. Previous study reported that the inhibition of autophagy significantly attenuated hepatic I/R injury10. However, the underlying mechanism associated with apoptosis and autophagy in hepatic I/R injury remains uncertain and this issue needs further study.…”