phenanthrenes and Nephrosis

Extracts of Tripterygium wilfordii Hook F have been used to treat glomerulonephritis for more than 30 years in China with dramatic antiproteinuric effects. Triptolide, a diterpene triepoxide, is one of the major active components of these extracts. To clarify its antiproteinuric effects we induced podocyte injury by puromycin aminonucleoside. Triptolide effectively reduced the proteinuria induced by puromycin in nephrotic rats without reducing the glomerular filtration rate. The antiproteinuric effect was associated with improvement in the foot process effacement, a decrease in the podocyte injury marker desmin as well as the restoration of nephrin and podocin expression and distribution. In cultured mouse podocytes triptolide pretreatment prevented the puromycin-induced disruption of the actin cytoskeleton and microfilament-associated synaptopodin while protecting nephrin and podocin expression. Triptolide suppressed reactive oxygen species generation and p38 mitogen-activated protein kinase activation while restoring RhoA signaling activity. These results show that triptolide ameliorates puromycin aminonucleoside-mediated podocyte injury in vivo and in vitro.

Topics: Animals; Cells, Cultured; Cholesterol; Cytoskeleton; Desmin; Diterpenes; Epoxy Compounds; Glomerular Filtration Rate; Intracellular Signaling Peptides and Proteins; MAP Kinase Signaling System; Membrane Proteins; Mice; Nephrosis; Phenanthrenes; Podocytes; Proteinuria; Puromycin Aminonucleoside; Rats; Reactive Oxygen Species; Serum Albumin; Triglycerides

Topics: Animals; Basement Membrane; Glycosides; Glycosuria; Guinea Pigs; Heart; In Vitro Techniques; Ketone Bodies; Kidney; Kidney Function Tests; Kidney Glomerulus; Kidney Tubular Necrosis, Acute; Kidney Tubules; Kidney Tubules, Proximal; Lethal Dose 50; Liver; Liver Function Tests; Natriuresis; Nephrosis; Oxidative Phosphorylation; Phenanthrenes; Potassium; Proteinuria; Rabbits; Rats; Time Factors