Protective effect of the mitochondria-targeted antioxidant Mito-Tempo against acute liver injury in mice with sepsis

Abstract:

Objective To investigate the effect of the mitochondria-targeted antioxidant Mito-Tempo on acute liver injury in mice with sepsis and its possible mechanisms.Methods C57BL/6 mice were randomly divided into control group（Control group），cecal ligation puncture group（CLP group），and Mito-Tempo treatment group（CLP+Mito-Tempo group）. Cecal ligation and puncture（CLP） was used to establish a mouse model of sepsis and acute liver injury，and the mice in the CLP+Mito-Tempo group were pretreated with intraperitoneal injection of Mito-Tempo at 1 hour before CLP treatment. After 24 hours，the mice were anesthetized and sacrificed，and HE staining was used to observe liver histopathological injury；ELISA was used to measure the serum levels of inflammatory factors，and immunofluorescent staining was used to measure the level of reactive oxygen species（ROS） in liver tissue；an electron microscope was used to observe the morphology of mitochondria；Western blot was used to measure the expression levels of cleaved cysteinyl aspartate specific proteinase 1（cleaved caspase-1），cleaved gasdermin D（GSDMD），interleukin-1α（IL-1α），and interleukin-1β（IL-1β）.Results Compared with the Control group，the CLP group had aggravation of liver injury，an increase in ROS level，destroyed mitochondrial morphology，and increases in the expression levels of the pyroptosis-related proteins cleaved caspase-1，cleaved GSDMD，IL-1α，and IL-1β. Compared with the CLP group，the CLP+Mito-Tempo group had alleviation of liver injury，a reduction in ROS level，partial restoration of mitochondrial morphology，and significant reductions in the expression levels of the pyroptosis-related proteins cleaved caspase-1，cleaved GSDMD，IL-1α，and IL-1β.Conclusion Mito-Tempo can alleviate acute liver injury in mice with sepsis，possibly by reducing the level of oxidative stress and inhibiting pyroptosis.