Hepatic 31P-magnetic resonance spectroscopy identified the impact of melatonin-pretreated mitochondria in acute liver ischaemia-reperfusion injury

Abstract

Acute liver ischaemia-reperfusion injury (IRI), commonly encountered during liver resection and transplantation surgery, is strongly associated with unfavourable clinical outcome. However, a prompt and accurate diagnosis and the treatment of this entity remain formidable challenges. This study tested the hypothesis that 31P-magnetic resonance spectroscopy (31P-MRS) findings could provide reliable living images to accurately identify the degree of acute liver IRI and melatonin-pretreated mitochondria was an innovative treatment for protecting the liver from IRI in rat. Adult male SD rats were categorized into group 1 (sham-operated control), group 2 (IRI only) and group 3 (IRI + melatonin [ie mitochondrial donor rat received intraperitoneal administration of melatonin] pretreated mitochondria [10 mg/per rat by portal vein]). By the end of study period at 72 hours, 31P-MRS showed that, as compared with group 1, the hepatic levels of ATP and NADH were significantly lower in group 2 than in groups 1 and 3, and significantly lower in group 3 than in group 1. The liver protein expressions of mitochondrial-electron-transport-chain complexes and mitochondrial integrity exhibited an identical pattern to 31P-MRS finding. The protein expressions of oxidative stress, inflammatory, cellular stress signalling and mitochondrial-damaged biomarkers displayed an opposite finding of 31P-MRS, whereas the protein expressions of antioxidants were significantly progressively increased from groups 1 to 3. Microscopic findings showed that the fibrotic area/liver injury score and inflammatory and DNA-damaged biomarkers exhibited an identical pattern of cellular stress signalling. Melatonin-pretreated mitochondria effectively protected liver against IRI and 31P-MRS was a reliable tool for measuring the mitochondrial/ATP consumption in living animals.