Protective Effect of Schisandrin B Against Cyclosporine A-Induced NephrotoxicityIn VitroandIn 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.

Pharmacokinetic and nephroprotective benefits of using Schisandra chinensis extracts in a cyclosporine A-based immune-suppressive regime

“…The salt-depleted rats underwent renal injury faster than rats on normal salt diet, and their kidneys showed morphological and pathological changes similar to those occurring in renal transplant patients. 42 In agreement with previous studies, 43 – 45 the present investigation revealed that administration of CsA results in deterioration of renal function as evidence by the marked elevation of serum urea and Cr levels. Furthermore, the development of CsA-induced renal dysfunction in the current investigation was accompanied by a rise in renal MDA levels along with a significant reduction in renal CAT activity and GSH-Px levels.…”

Protective effects of schizandrin and schizandrin B towards cisplatin nephrotoxicity in vitro

“…Nevertheless, these promising results are to be related to a potential reduction in the loss of tubular cells in vivo, what could reduce tubular atrophy and AKI. This has notably been demonstrated for Schi B in a cyclosporine A-mediated nephrotoxicity model (Zhu et al, 2012).…”

“…1 (Panossian and Wikman, 2008). These compounds have been involved in recent in vivo and in vitro pharmacological studies, suggesting a protective effect in various pathological models (Jeong et al, 2012;Lee et al, 2012), with some studies focusing on nephrotoxicity (Park et al, 2012;Sohn et al, 2009aSohn et al, ,2009bStacchiotti et al, 2011;Zhu et al, 2012).…”

Synergy and Antagonism of Active Constituents of ADAPT-232 on Transcriptional Level of Metabolic Regulation of Isolated Neuroglial Cells

“…Schizandrin B was shown to increase the intracellular ATP levels and to protect against Gentamicin and Cyclosporine A-induced nephrotoxicity by decreasing oxidative stress and cell death in vitro and in vivo (Chiu et al, 2008; Zhu et al, 2012). R. rosea extract activated the synthesis or resynthesis of ATP in skeletal muscles mitochondria and stimulated reparative energy processes after intense exercise in rats.…”