Antioxidative Stress Effects of <b><i>Salvia przewalskii</i></b> Extract in Experimentally Injured Podocytes

Abstract

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 μg/ml), SPE (158, 316 μg/ml), SalB (8.5, 17 μg/ml) and RA (25, 50 μg/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 mitochondrial 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 mitochondrial fragmentation increased significantly following PAN exposure in podocytes (p < 0.05). Treatment with high-dose SalB 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 significantly attenuated 8-OHdG in PAN nephrosis. Antioxidative stress effects of high-dose SPE, SalB against PAN-stimulated cultured podocyte via mechanisms include suppression of ROS expression and mitochondria fission. In addition, SPE, SalB and RA can suppress PAN-induced apoptosis.

Overproduction of Mitochondrial Fission Proteins in Membranous Nephropathy in Children

“…In previous studies, we [15] and other groups [16,17] observed that mitochondrial fragmentation was involved in podocyte injury in cultured podocytes. In addition, our previous study found a correlation between the overproduction of glomerular mitochondrial fission proteins, including Drp1, phospho-Drp1 (Ser616) and Fis1, and proteinuria in adriamycin nephropathy in rats [18].…”

Evaluation of antigenotoxic potential of salvianolic acid B with hydrogen peroxide on human peripheral blood leukocytes in vitro

“…Osim što ispoljava protektivni efekat protiv direktnog dejstva slobodnih radikala, utvrđeno je i da štiti od toksičnih dejstava lekova na kardiomiocitima (20,21). Pokazano je i da Sal B, zahvaljujući svom antioksidativnom kapacitetu, sprečava oksidativna oštećenja mitohondrijske DNK in vitro i in vivo u ćelijama bubrega (22).…”

“…Ovi rezultati su u skladu s podacima studije u kojoj je utvrđeno da u terapijskoj koncentraciji od 50 μg/ml, čak i u dvostruko većoj koncentraciji od terapijske (100 μg/ml), preparati koji sadrže Sal B nisu značajno uticali na normalnu sintezu DNK u kardiomiocitima, dok tek u koncentraciji većoj od 200 μg/ml mogu da dovedu do smanjene sinteze DNK (36). S druge strane, pokazano je da Sal B ima sposobnost da redukuje oksidaciju mitohondrijske DNK i produkciju 8-OHdG u ćelijama bubrega in vitro i in vivo (22). vitro.…”

Salvia przewalskii extract of total phenolic acids inhibit TLR4 signaling activation in podocyte injury induced by puromycin aminonucleoside in vitro

“…Our previous study showed that SPE can reduce proteinuria, protect podocyte cytoskeletons and restore the expression of genes critical for podocyte structure and function in rats with nephrosis induced by PAN [ 5 ]. Our further study showed that SPE also attenuates the production of 8-OHdG in PAN nephrosis [ 6 ]. SPE and the monomers can reduce ROS production and prevent mitochondrial fission in PAN-treated podocytes.…”

“…The antioxidant effect of high-dose SPE and SalB in PAN-treated cultured podocyte is through suppression of ROS production and mitochondrial fission. In addition, we also found that SPE, SalB and RA can suppress PAN-induced apoptosis in podocytes [ 6 ].…”