Hepatoprotective Effect of Mitochondria-Targeted Antioxidant Mito-TEMPO against Lipopolysaccharide-Induced Liver Injury in Mouse

Abstract

The liver is vulnerable to sepsis, and sepsis-induced liver injury is closely associated with poor survival of sepsis patients. Studies have found that the overproduction of reactive oxygen species (ROS) is the major cause of oxidative stress, which is the main pathogenic factor for the progression of septic liver injury. The mitochondria are a major source of ROS. Mito-TEMPO is a mitochondria-specific superoxide scavenger. The aim of this study was to investigate the effect of Mito-TEMPO on lipopolysaccharide- (LPS-) induced sepsis mice. We found that Mito-TEMPO pretreatment inhibited inflammation, attenuated LPS-induced liver injury, and enhanced the antioxidative capability in septic mice, as evidenced by the decreased MDA content and the increased SOD activity. In addition, Mito-TEMPO restored mitochondrial size and improved mitochondrial function. Finally, we found that the levels of pyroptosis-related proteins in the liver of LPS-treated mice were lower after pretreatment with Mito-TEMPO. The mechanisms could be related to Mito-TEMPO enhanced antioxidative capability and improved mitochondrial function, which reflects the ability to neutralize ROS.

Mitokondri hedefli bir antioksidan olan Mito-TEMPO’nun donmuş insan sperm parametrelerine etkisi

“…They have become possible ways to keep sperm from getting damaged by the stress of being frozen (24). Mitochondria is an important organelle for cell energy metabolism that modulates redox mechanism, cell development and death (9). Spermatozoa get energy for their metabolism from mitochondria through ATP synthase and oxidative phosphorylation.…”

Dachengqi decoction ameliorates sepsis-induced liver injury by inhibiting the TGF-β1/Smad3 pathways

“…MS analysis was performed on a Thermo Scientific Qexactive Focus Orbitrap MS (Thermo Electron, Bremen, Germany) operated with heated electrospray ionization (HESI) in positive and negative ion modes. The mass spectra were acquired in full MS mode in a mass range from m / z 100−1200 at a resolution of 70,000, combined with the data-dependent scan (dd-MS 2 ) at a resolution of 35,000 and an isolation window of m / z 3.0. Other Q-Exactive general parameters were as follows: nebulizer pressure at 10 arb, sheath gas and auxiliary gas at a flow rate of 30 arb, capillary temperature at 320 °C, auxiliary gas heater temperature at 350 °C, spray voltage at 3.2 kV, and S-lens level at 50.…”

“…Sepsis is a systemic multiorgan dysfunction caused by a dysregulated host response to infectionand is the leading cause of death in intensive care unit patients. 1 , 2 Although advanced antibiotic regimens have been applied in current clinical practice, the mortality of sepsis patients remains high. 3 , 4 The liver is an important organ that plays a fundamental physiological role in metabolism, 5 and sepsis-induced acute liver injury (ALI) is a strong independent predictor of intensive care unit mortality in patients with sepsis.…”

“…Sepsis is characterized by an overactivated inflammatory response, 2 and accumulating evidence demonstrates that oxidative stress plays an important role in the pathogenesis of sepsis. 8 , 9 The liver is one of the common organs associated with sepsis injury, and sepsis-induced ALI involves a series of complex pathological mechanisms, including inflammation, the immune response, cellular hypoxia, oxidative stress, and apoptosis.…”

Sinapic Acid Attenuate Liver Injury by Modulating Antioxidant Activity and Inflammatory Cytokines in Thioacetamide-Induced Liver Cirrhosis in Rats

“…The homogenate liver tissues were prepared via Teflon homogenizer (performed on ice), and then centrifuged at 4500 rpm for 15 min at 4 • C excluding cell debris. The collected supernatant was examined for antioxidant actions by using superoxide dismutase (SOD) and catalase (CAT) kits (Cayman Chemical Company, Ann Arbor, MI, USA) [39]. Malondialdehyde (MDA), as a lipid peroxidation biomarker, was also assessed to analyze the level of oxidative stress.…”