Figure 1.
MA-5 rescued the IRI kidney model, and the direct effects of MA-5 on mitochondria are shown. (A) Plasma concentration of MA-5 after oral administration at a dose of 25, 50, or 150 mg/kg (n=3). (B) Plasma creatinine (Cr), KIM-1 immunostaining–positive area, and acute tubular necrosis (ATN) score of kidney histology were significantly reduced in MA-5–treated mice 48 hours after IRI surgery (vehicle [Veh] sham, n=4; Veh IRI, n=5; MA-5 IRI, n=6). KIM-1 stain (×20 and ×100 magnification) and periodic acid–Schiff (PAS) stain (magnification ×200) of the kidney pathology 48 hours after sham or IRI surgery. *P<0.05; **P<0.01 (two-way ANOVA and Tukey post hoc test for plasma Cr, unpaired two–tailed t test for KIM-1 area, and ATN score versus Veh IRI). (C) Plasma BUN and ATN score of kidney histology were significantly reduced in the MA-5–treated mice 96 hours after cisplatin administration (vehicle [Veh] -CIN, n=7; MA-5-CIN, n=8). PAS stain (magnification ×200) of the kidney pathology 96 hours after intraperitoneal cisplatin injection. *P<0.05 (two-way ANOVA and Tukey post hoc test for plasma BUN and unpaired two–tailed t test for ATN score versus Veh-CIN). (D) ATP production of isolated detergent–solubilized rat hepatic mitochondria with or without MA-5 (10 μM; n=5). ADP (64 nM) was added to the reaction medium. (E) Respiration rate of mitochondria in states 2–4. (F) Mitochondrial ROS production in mouse cardiac mitochondria was measured with DMSO (0.1%) or MA-5 (10 μM; n=5). (G) Effect of MA-5 on the activities of complexes I–IV using detergent–solubilized bovine heart mitochondria (n=3 for complex I experiment; n=6 for complexes II–IV experiments). *P<0.05 (unpaired two–tailed t test versus DMSO). KCN, potassium cyanide; mOD, milli optical density; RLU, relative luciferase unit; TTFA, 2- thenoyltrifluoroacetone.