Journal
NEPHRON
Volume 134, Issue 4, Pages 253-271Publisher
KARGER
DOI: 10.1159/000448223
Keywords
Puromycin aminonucleoside; Podocyte; Total phenolic acid of Salvia przewalskii; Salvianolic acid B; Rosmarinic acid; 8-Hydroxy-2 '-deoxyguanine; Reactive oxygen species; Mitochondria; Apoptosis
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Funding
- Technical Innovation Foundation Projects from Nanjing Military Region Medical Scientific [15DX008]
- National Natural Science Foundation of China [81370790]
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Background: Oxidative stress is a leading cause of puromycin aminonucleoside (PAN)-induced nephrosis. As the inhibition of oxidative stress may improve injury of podocyte, we aimed at examining the effect of total phenolic acid extract of Salvia przewalskii (SPE) on PAN-induced oxidative stress in vivo and in vitro. Methods: Seventy-two male Sprague Dawley rats were randomly assigned into 6 groups (n = 12), PAN alone, tacrolimus (TAC), SPE (50, 100 and 200 mg/kg) and normal control group. Salvianolic acid B (SalB, 5.52%) and rosmarinic acid (RA, 31.58%) were isolated from SPE. The intensities of 8-oxo-2'-deoxyguanosine (8-OHdG) were evaluated by immunofluorescence. In vitro, the podocytes were assigned into groups of control, PAN alone, TAC (1 mu g/ml), SPE (158, 316 mu g/ml), SalB (8.5, 17 mu g/ml) and RA (25, 50 mu g/ml). The intracellular reactive oxygen species (ROS) production and cell apoptosis rate were measured by flow cytometry. Form factor and aspect ratio were calculated to assess mitochondria! morphology. Results: In vivo, PAN increased the intensity of 8-OHdG in the renal tissue in the PAN group (p < 0.05). The high-dose SPE reduced 8-OHdG significantly at levels comparable to TAC alone (p > 0.05) on day 15. The intracellular ROS production, podocytes apoptosis rate and mitochondria! fragmentation increased significantly following PAN exposure in podocytes (p < 0.05). Treatment with high-dose SaIB significantly ameliorated the increase in the expression of ROS and revised the structure of mitochondria. The percentage of apoptotic cells was decreased compared with the PAN group after SPE, SalB, RA, and TAC treatment for 24 h (p < 0.05). Conclusion: These findings suggest that high-dose SPE significantlyattenuated 8-OHdG in PAN nephrosis. Antioxidative stress effects of high-dose SPE, SaIB against PAN-stimulated cultured podocyte via mechanisms include suppression of ROS expression and mitochondria fission. In addition, SPE, SaIB and RA can suppress PAN-induced apoptosis. (C) 2016 S. Karger AG, Basel
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