Hepatic³¹P‐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.

Mitochondrial transplantation therapy for ischemia reperfusion injury: a systematic review of animal and human studies

“…Studies on mitochondrial transplantation have also been conducted in other experimental models including acute limb ischemia [ 45 ], lung IRI [ 46 ], spinal cord injury [ 47 ], and acute liver injury [ 48 ] models. Orfany et al [ 45 ] used a C57BL/6 J male mouse acute limb ischemia model to compare the impact of dose-dependent mitochondrial injection (1 × 10 6 , 1 × 10 7 , 1 × 10 8 , and 1 × 10 9 mitochondria/g muscle) after IRI with f-Rhodamine 6G-labeled mitochondria.…”

“…They found that mitochondrial transplantation significantly reduced neuronal apoptosis and improved locomotor function in rats with spinal cord ischemia by suppressing oxidative stress and endoplasmic reticulum (ER) stress [ 47 ]. Ko et al [ 48 ] investigated whether 31 P-magnetic resonance spectroscopy ( 31 P-MRS) could accurately identify the protective effects of transplanting melatonin-pretreated mitochondria (m-Mito) on acute liver IRI in rats. At 72 h after acute liver IRI, 31 P-MRS showed that the hepatic levels of ATP and NADH were significantly higher in the m-Mito group than in the IRI group.…”

“…At 72 h after acute liver IRI, 31 P-MRS showed that the hepatic levels of ATP and NADH were significantly higher in the m-Mito group than in the IRI group. Histopathology revealed that the liver injury score and inflammatory cell infiltration in the liver parenchyma were significantly decreased with the m-Mito-transplanted IRI group [ 48 ].…”

Potential Role of Melatonin as an Adjuvant for Atherosclerotic Carotid Arterial Stenosis

“…However, due to the limited sample size and short follow-up, there was no data on the effect of melatonin on the recurrent stroke and other post-operative complications. Although the clinical evidence of melatonin treating CAS-induced cerebral I/R injury is limited, its protective effects of targeted organs against I/R injury in the heart [14], intestine [47], liver [48], and kidney [49] have been demonstrated elsewhere, which indirectly supported the potential benefit of melatonin, alleviating cerebral I/R injury after CAS revascularization.…”

Requirements for successful mitochondrial transplantation

“…Moskowitzova et al [26] isolated syngeneic mitochondria from gastrocnemius muscle of C57BL/6J mice. Ko et al [40] reported that mitochondrial isolation was performed with 3 g of rat liver samples.…”