title: Protective effect of schisandrin B against cyclosporine A-induced nephrotoxicity in vitro and in vivo.
abstract: Schisandrin B (Sch B) is an active ingredient of the fruit of Schisandra chinensis. It has many therapeutic effects arising from its tonic, sedative, antitussive and antiaging activities and is also used in the treatment of viral and chemical hepatitis. The aim of this study was to investigate the protective effects of Sch B on cyclosporine A (CsA)-induced nephrotoxicity in mice and HK-2 cells (a human proximal tubular epithelial cell line). After gavage with Sch B (20 mg/kg) or olive oil (vehicle), mice received CsA (30 mg/kg) by subcutaneous injection once daily for four weeks. Renal function, histopathology, and tissue glutathione (GSH) and malondialdehyde (MDA) levels were evaluated after the last treatment. The effects of Sch B on CsA-induced oxidative damage in HK-2 cells were investigated by measuring cell viability, the release of lactate dehydrogenase (LDH), the level of reactive oxygen species (ROS), and the cellular GSH and ATP concentrations. Cellular apoptosis was assessed by flow cytometry. Treatment with Sch B in CsA-treated mice significantly suppressed the elevation of blood urea nitrogen (BUN) and serum creatinine levels and attenuated the histopathological changes. Additionally, Sch B also decreased renal MDA levels and increased GSH levels in CsA-treated mice. Using an in vitro model, Sch B (2.5, 5 and 10 μM) significantly increased the cell viability and reduced LDH release and apoptosis induced by CsA (10 μM) in HK-2 cells. Furthermore, Sch B increased the intracellular GSH and ATP levels and attenuated CsA-induced ROS generation. In conclusion, Sch B appears to protect against CsA-induced nephrotoxicity by decreasing oxidative stress and cell death.
authors: School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
authors: Shaohua
authors: S
authors: Zhu
authors: Yan
authors: Y
authors: Wang
authors: Meiwan
authors: M
authors: Chen
authors: Jing
authors: J
authors: Jin
authors: Yuwen
authors: Y
authors: Qiu
authors: Min
authors: M
authors: Huang
authors: Zhiying
authors: Z
authors: Huang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001806:Blood Urea Nitrogen; D002470:Cell Survival / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D034242:Cyclooctanes / Q000494:pharmacology / Q000627:therapeutic use; D016572:Cyclosporine / Q000009:adverse effects*; D004791:Enzyme Inhibitors / Q000009:adverse effects; D005638:Fruit; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D011083:Polycyclic Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D032141:Schisandra / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D034242:Cyclooctanes; D004791:Enzyme Inhibitors; D017705:Lignans; D010936:Plant Extracts; D011083:Polycyclic Compounds; D017382:Reactive Oxygen Species; C015499:schizandrin B; D008315:Malondialdehyde; D016572:Cyclosporine; D000255:Adenosine Triphosphate; D003404:Creatinine; D007770:L-Lactate Dehydrogenase; D005978:Glutathione