phenanthrenes and Ureteral-Obstruction

Oxidative stress and inflammatory responses are closely implicated in the progression of renal interstitial fibrosis, thereby leading to chronic kidney disease. Cryptotanshinone (CTS) is a natural compound involved in antioxidant and anti-inflammatory activities. We evaluated the effects of CTS on inflammation and oxidative stress in obstructed kidneys. Mice received gastric gavage of CTS from 7 days before unilateral ureteral obstruction operation to 1 week after surgery. Administration of CTS at 50 and 100 mg/kg/day significantly decreased collagen production, as shown by Masson staining. Immunohistochemistry staining and RT-PCR confirmed that CTS reduced extracellular matrix proteins, such as fibronectin and collagen-1, in the obstructed kidneys in a dose-dependent manner. Furthermore, immunohistochemistry staining indicated that CTS inhibited infiltration of the macrophage (CD68-positive) and lymphocyte (CD3-positive) cells, which were associated with the suppression of the nuclear factor-κB signalling activation. CTS increased superoxide dismutase, catalase and glutathione while decreased malondialdehyde production. More importantly, CTS activated Nrf-2 and HO-1 in the obstructed kidneys for 7 days. CTS could protect renal interstitial fibrosis by ameliorating inflammation and oxidative stress, which might be through the regulation of NF-κB and Nrf-2/HO-1 signalling pathways.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Blotting, Western; Inflammation; Kidney; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Phenanthrenes; Real-Time Polymerase Chain Reaction; Ureteral Obstruction

Extracts of Tripterygium wilfordii Hook F. have been used to treat glomerulonephritis for more than 30 years in China. Most of the anti-inflammatory and immunosuppressive activities of these extracts can be attributed to triptolide (Trip). The present study was to investigate the effect of Trip on renal interstitial fibrosis in a model of unilateral ureteral obstruction (UUO).. UUO or sham-operated rats were randomly assigned to receive mycophenolate mofetil (MMF), Trip or vehicle and were killed on days 7 and 14 after UUO or sham operation. Kidney specimens were fixed for immunohistochemistry for myofibroblasts (α-smooth muscle actin, α-SMA), macrophages (ED-1), monocyte chemoattractant protein-1 (MCP-1) and osteopontin. Interstitial collagen deposition and amounts of transforming growth factor-β1 (TGF-β1) were determined by Sirius red staining and enzyme-linked immunosorbent assay, respectively. The mRNA expression of TGF-β1, connective tissue growth factor (CTGF), MCP-1 and osteopontin were measured by real-time polymerase chain reaction analysis.. The scores for the density of α-SMA- and ED-1-positive cells, the staining of MCP-1 and osteopontin, interstitial collagen deposition and amounts of TGF-β1 were significantly reduced by MMF or Trip. MMF or Trip significantly reduced the mRNA expression of TGF-β1, CTGF, MCP-1 and osteopontin.. Trip significantly attenuated tubulointerstitial fibrosis in a rat UUO model and the effect of Trip on renal fibrosis was similar to that of MMF. Trip may be useful as a potential candidate in the treatment of renal fibrosis.

Topics: Actins; Analysis of Variance; Animals; Chemokine CCL2; Collagen; Connective Tissue Growth Factor; Diterpenes; Epoxy Compounds; Fibrosis; Immunosuppressive Agents; Kidney; Macrophage Activation; Male; Osteopontin; Phenanthrenes; Rats; Rats, Sprague-Dawley; RNA, Messenger; Transforming Growth Factor beta1; Ureteral Obstruction