Mitochondrial permeability transition as a novel principle of hepatorenal toxicity in vivo.

摘要: Atractyloside (Atr) binds to the adenine nucleotide translocator (ANT) and inhibits ANT-mediated ATP/ADP exchange on inner mitochondrial membrane. In addition, Atr can trigger opening of a non-specific ion channel, within ANT-containing permeability transition pore complex (PTPC), which is subject redox regulation inhibited by cyclosporin A (CsA). Here we show that cytotoxic effects Atr, both in vivo vitro, are determined its capacity induce PTPC consequent membrane permeabilization (MMP). Thus, Atr-induced MMP death cultured liver cells CsA as well glutathione (GSH) enhanced GSH depletion. Similarly, hepatorenal toxicity assessed vivo, was reduced treating mice with or diet rich sulfur amino acids, regime enhances levels. injection induced hepatocytes proximal renal tubular cells, either GSH. Acetaminophen (paracetamol)-induced acute poisoning also attenuated GSH, vitro vivo. Altogether these data indicate PTPC-mediated may determine xenobiotics