(melle-4)cyclosporin and Hyperoxaluria

To experimentally evaluate the clinical application of N-methyl-4-isoleucine cyclosporin, a novel selective inhibitor of cyclophilin D activation.. In vitro, cultured renal tubular cells were exposed to calcium oxalate monohydrate crystals and treated with N-methyl-4-isoleucine cyclosporin. The mitochondrial membrane was stained with tetramethylrhodamine ethyl ester perchlorate and observed. In vivo, Sprague-Dawley rats were divided into four groups: a control group, an ethylene glycol group (administration of ethylene glycol to induce renal calcium crystallization), a N-methyl-4-isoleucine cyclosporin group (administration of N-methyl-4-isoleucine cyclosporin) and an ethylene glycol + N-methyl-4-isoleucine cyclosporin group (administration of ethylene glycol and N-methyl-4-isoleucine cyclosporin). Renal calcium crystallization was evaluated using Pizzolato staining. Oxidative stress was evaluated using superoxide dismutase and 8-hydroxy-deoxyguanosine. Mitochondria within renal tubular cells were observed by transmission electron microscopy. Cell apoptosis was evaluated using cleaved caspase-3.. In vitro, calcium oxalate monohydrate crystals induced depolarization of the mitochondrial membrane potential, which was remarkably prevented by N-methyl-4-isoleucine cyclosporin. In vivo, ethylene glycol administration induced renal calcium crystallization, oxidative stress, mitochondrial collapse and cell apoptosis in rats, which were significantly prevented by N-methyl-4-isoleucine cyclosporin.. Herein we first report a new treatment agent determining renal calcium crystallization through cyclophilin D activation.

Topics: Animals; Apoptosis; Calcium Oxalate; Cell Line; Cyclophilins; Cyclosporine; Enzyme Inhibitors; Hyperoxaluria; Kidney Tubules, Proximal; Male; Membrane Potential, Mitochondrial; Microscopy, Electron, Transmission; Mitochondria; Oxidative Stress; Peptidyl-Prolyl Isomerase F; Rats, Sprague-Dawley