Mitochondrial dysfunction is involved in the pathogenesis of chronic kidney disease and acute kidney injury (AKI). Mitochonic acid 5 (MA-5) is a synthesized indole acetic acid derivative that facilitates ATP production, reduces the level of mitochondrial reactive oxygen species, and targets mitochondrial protein mitofilin. MA-5 binds to mitofilin with a Bmax value of 12.5±4.35ng and a Kd value of 28.2±11.4µM[1]. MA-5 at 1-10µM dose-dependently inhibited TNFα-induced apoptosis in mouse microglial BV-2 cells. Treatment with MA-5 at 5µM increased mitochondrial potential and decreased the level of mitochondrial calcium in TNFα-treated cells[2]. In a bilateral ischemia-reperfusion injury (IRI) model, oral administration of MA-5 at 25, 50, or 150mg/kg significantly improved plasma creatinine level after reperfusion compared to the vehicle-treated IRI mice. MA-5 treatment also significantly decreased the expression of AKI marker, KIM-1, at the outer medullar and the acute tubular necrosis score in IRI mice at 48h post-treatment. In a mouse model of cisplatin-induced nephropathy (CIN), MA-5 (50mg/kg)-treated mice showed significantly reduced plasma BUN 96h after cisplatin administration compared to the vehicle-treated CIN animals[1].
作用机制
Mitochonic acid 5 is a synthesized indole derivative that regulates mitochondrial ATP synthesis independently of electron transport chain and oxidative phosphorylation[1].
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