ursodoxicoltaurine and Kidney-Diseases

Chronic high salt intake exaggerates renal injury and inflammation, especially with the loss of functional ET. In ET. TUDCA protects against the development of glomerular and proximal tubular damage, decreases renal cell death and inflammation in the renal cortex in rats with ET

Topics: Animals; Animals, Genetically Modified; Gene Deletion; Inflammation; Kidney Diseases; Male; Random Allocation; Rats; Receptor, Endothelin B; Sodium Chloride, Dietary; Taurochenodeoxycholic Acid

Chronic exposure to cyclosporine causes nephrotoxicity and organ damage. Here we show that cyclosporine nephrotoxicity in vivo is associated with the activation of the unfolded protein response (UPR) pathway to initiate tissue fibrosis. We demonstrate that cyclosporine therapy activated the IRE1α branch of the unfolded protein response (UPR) and stimulated the TGFβ1 signaling pathway in the kidneys of male mice. Co-administration of the proteostasis promoter tauroursodeoxycholic acid (TUDCA) with cyclosporine inhibited the UPR pathway in the kidneys of treated male mice as well as decreased the development of renal fibrogenesis.

Topics: Animals; Cyclosporine; Disease Models, Animal; Fibrosis; Kidney; Kidney Diseases; Male; Mice; Taurochenodeoxycholic Acid; Unfolded Protein Response

Aldosterone (Aldo) is critically involved in the development of renal injury via the production of reactive oxygen species and inflammation. Endoplasmic reticulum (ER) stress is also evoked in Aldo-induced renal injury. In the present study, we investigated the role of ER stress in inflammation-mediated renal injury in Aldo-infused mice. C57BL/6J mice were randomized to receive treatment for 4 weeks as follows: vehicle infusion, Aldo infusion, vehicle infusion plus tauroursodeoxycholic acid (TUDCA), and Aldo infusion plus TUDCA. The effect of TUDCA on the Aldo-infused inflammatory response and renal injury was investigated using periodic acid-Schiff staining, real-time PCR, Western blot, and ELISA. We demonstrate that Aldo leads to impaired renal function and inhibition of ER stress via TUDCA attenuates renal fibrosis. This was indicated by decreased collagen I, collagen IV, fibronectin, and TGF-

Topics: Aldosterone; Animals; Blotting, Western; Endoplasmic Reticulum; Enzyme-Linked Immunosorbent Assay; Kidney; Kidney Diseases; Mice; Mice, Inbred C57BL; Reactive Oxygen Species; Real-Time Polymerase Chain Reaction; Taurochenodeoxycholic Acid