Mito Q Protects Rodent Kidneys From Ischemia Reperfusion Injury Using T2WI And DCE-MRI

Objectives: This study aims to investigate the effect of the mitochondria targeted antioxidant Mito Q in protecting from renal ischemia-reperfusion injury?IRI?in a rat model.The efficacy is assessed by the longitudinal observation by T2-weighed imaging?T₂WI?and dynamic contrast-enhanced magnetic resonance imaging?DCE-MRI?with quantitative estimations of unilateral renal dynamic parameters.Materials and Methods: This study was approved by Tianjin Medical University General Hospital Animal Care and Use Committee.Twenty male Sprague–Dawley rats?Beijing University Health Science Center?with an average weight of 250 g were randomly divided into four groups: Group I?IRI with Mito Q treatment,n = 5?,the rats were administered with Mito Q?donated by Antipodean Pharmaceuticals Inc.: 2.8mg/kg in 700 ?L 0.9% saline?15 min prior to the onset of warm ischemia via infusion into the tail vein at an injection rate of 20 u L/s,then subjected to left renal ischemia for 45 min followed by reperfusion;Group II?IRI with saline treatment,n =5?,who underwent the same procedure as Group I except that the injectant was 700?L 0.9% saline;Group III?normal kidneys with Mito Q treatment,n = 5?,the rats were administered with Mito Q in the same way as in Group I but without the IRI procedure;Group IV?normal kidneys with saline treatment,n = 5?,the rats were administered with saline in the same way as in Group II but without the IRI procedure.MRI was performed before the operation?day 0?and on day 2,5,7 and 14 after the operation using a 3T MRI.T2-weighted standardized signal intensity?SSI?of the outer stripe of the outer medulla?OSOM?was measured on bilateral kidneys.Multiphasic DCE-MRI was acquired and unilateral renal clearance rate k_cl,which indicated the transportation rate of the contrast medium Gd-DTPA from the renal cortex to the medulla,was derived from the time-intensity curve?TIC?using a mathematic algorithm.Renal histopathology damage score was evaluated after the final MRI examination.The differences of SSI and k_cl values between the groups at different time points were assessed using Least Significant Difference?LSD?.Kruskal-Wallis H test and Mann-Whitney U test were used for histopathology damage score analyses.Results:1.SSI of the OSOM on IRI kidneys were higher than their counterparts at all time points after IRI in four groups.SSI of the OSOM on IRI kidneys in Group I on day 5 and day 7 were lower than those in Group II?day 5,Group I VS.Group II,4.10±0.64,4.95±0.59,P = 0.004;day 7,Group I VS.Group II,4.78±0.97,6.40±0.94,P < 0.001?.2.Kcl values of IRI kidneys in four groups were lower than their counterparts at all time points,k_cl values of IRI kidneys in Group I were higher than those in Group II after IRI?day 2,Group I VS.Group II,1.64±0.24,1.29±0.15,P = 0.002;day 5,Group I VS.Group II,1.92±0.18,1.22±0.28,P < 0.001;day 7,Group I VS.Group II,2.07±0.29,1.60±0.30,P = 0.001;day 14,Group I VS.Group II,2.19±0.24,1.64±0.28,P < 0.001?.3.Renal histopathology analysis showed that renal damage was the most predominant on the OSOM of IRI kidneys in Group II,whose histopathology damage scores were significantly higher than those in Group I?P < 0.001?.The pathological changes in the other kidneys were little.Conclusions:The findings on T₂WI showed that renal IRI was the most predominant on the OSOM,the changes on other stripes were little;SSI and k_cl values confirmed the presence of renal IRI,and k_cl values demonstrated Mito Q's protective effect on renal IRI,which could be further confirmed by the renal histopathology analysis.