Hepatic 31 P-magnetic resonance spectroscopy identified the impact of melatonin-pretreated mitochondria in acute liver ischaemia-reperfusion injury.
Sheung-Fat KoYi-Ling ChenPei-Hsun SungJohn Y ChiangYi-Ching ChuChung-Cheng HuangChi-Ruei HuangHon-Kan YipPublished in: Journal of cellular and molecular medicine (2020)
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 31 P-magnetic resonance spectroscopy (31 P-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, 31 P-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 31 P-MRS finding. The protein expressions of oxidative stress, inflammatory, cellular stress signalling and mitochondrial-damaged biomarkers displayed an opposite finding of 31 P-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 31 P-MRS was a reliable tool for measuring the mitochondrial/ATP consumption in living animals.
Keyphrases
- oxidative stress
- drug induced
- liver injury
- liver failure
- cell death
- diabetic rats
- dna damage
- ischemia reperfusion injury
- respiratory failure
- reactive oxygen species
- acute myocardial infarction
- endoplasmic reticulum
- clinical trial
- mesenchymal stem cells
- high resolution
- amino acid
- single molecule
- cerebral ischemia
- protein protein
- brain injury
- acute coronary syndrome
- systemic sclerosis
- acute respiratory distress syndrome
- hepatitis b virus
- extracorporeal membrane oxygenation
- cell therapy
- optical coherence tomography
- bone marrow
- percutaneous coronary intervention
- mechanical ventilation
- left ventricular
- young adults
- heat shock protein
- cell free
- stem cells
- small molecule