Mitochondria‐targeted antioxidant MitoQ reduced renal damage caused by ischemia‐reperfusion injury in rodent kidneys: Longitudinal observations of T2‐weighted imaging and dynamic contrast‐enhanced MRI

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Nephron‐sparing nephrectomy has been accepted as the standard surgical procedure for the treatment of small renal tumors and in patients with bilateral tumors 1. Temporary renal artery occlusion is essential during the operation to prevent intraoperative bleeding and to provide a bloodless surgical field 3. Hence, warm ischemia and subsequently renal ischemia‐reperfusion injury (IRI) are inevitable and are a major cause of postoperative renal functional decline 4. Kalogeris et al. 6 proposed that pharmacological preconditioning could contribute to the activation of cell survival mechanisms and protection of the kidneys from IRI. The search for novel medical interventions is of great research interest 7. Cell death programs activated by ischemia and reperfusion are related to apoptosis, necrosis, autoimmune responses, and enhanced reactive oxygen species (ROS) generation, and there might be a reciprocity between the programs and mitochondrial oxidative damage in the early phases of IRI 8. The oxidative stress caused by excessive amounts of ROS during IRI could alter mitochondrial oxidative phosphorylation and activate membrane phospholipids proteases, and more importantly, oxygen free radicals during reperfusion could result in lipid peroxidation 10. As mitochondrial oxidative damage is central to IRI damage, decreasing mitochondrial oxidative activity during IRI could be a potential therapeutic approach. Because untargeted cellular antioxidants cannot accumulate in mitochondria and they are not protective 11, Murphy et al. developed the mitochondria‐targeted antioxidant MitoQ. MitoQ is conjugated to a lipophilic cation that can rapidly pass through the mitochondria phospholipid bilayer and accumulate within the mitochondria with the help of the electrochemical gradient 11.
Magnetic resonance imaging can provide excellent morphologic and functional information for evaluating renal pathophysiology noninvasively in vivo, and is suitable for repeated measurements. The differences between T2 relaxation times for different tissues enable MRI to be used in the evaluation of morphologic changes with high spatial resolution 12. The severity of renal IRI damage varies in different regions. Hueper et al. demonstrated that the T2 values of the outer stripe of the outer medulla (OSOM) could be used to distinguish between severe injury and moderate injury after IRI in mice 13. This capability probably exists because the thick ascending limb of Henle's loop and the S3 segment of the proximal tubule in the OSOM consume far more oxygen than any other parts to achieve sodium balance involving active reabsorption 14. It has been well documented that renal functional parameters obtained from dynamic contrast‐enhanced MRI (DCE‐MRI) are closely correlated with radionucllde renography parameters 15. Baumann and Rudin proposed that the first‐order rate constant kcl, which reflected tracer transportation from the renal cortex to the medulla in the initial phase of DCE‐MRI, might provide a good estimation of the kidney clearance rate 16. Laurent et al. 17 further demonstrated that kcl data estimated by DCE‐MRI correlated well with glomerular filtration rate values assessed using the inulin clearance assay. In this setting, the left renal artery was clamped and the right kidneys were kept as controls, which made this variable ideal for comparisons to reveal renal morphologic and functional changes bilaterally in living animals. It would be beneficial, both methodologically and ecologically, if the quantitative estimations of T2 signal intensities of the OSOM and kcl values obtained from DCE‐MRI before and after IRI could noninvasively reveal the severity of renal damage, and be used to evaluate the effect of medical pretreatment in protecting against IRI.
The aim of the study was to investigate the effect of MitoQ in reducing the severity of renal damage caused by IRI in rats based on the longitudinal observations of T2‐weighted imaging and DCE‐MRI with quantitative estimations of unilateral renal dynamic parameters.

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