Tanshinone IIA attenuates renal injury during hypothermic preservation via the MEK/ERK1/2/GSK-3β pathway

Abstract

Abstract Background Oxidative stress-induced injury during hypothermic preservation is a universal problem that delays graft function and decrease the success of organ transplantation. Tanshinone IIA (Tan IIA) was reported to exhibit a variety of biochemical activities, including protection against oxidative stress. Therefore, the specific molecular pathway by which Tan IIA protects renal tissues during preservation was investigated in this study. Methods In vivo study, Sprague-Dawley (SD) rats were divided into twelve groups and the kidneys were isolated and preserved in different solutions for 0, 24 or 48 h, respectively: control group (Celsior solution) and Tan II groups (Celsior solution containing 10, 50,100 μM). In vitro study, primary renal cell from SD rats was cultured which was treated H2O2 (800 μM) for 6 h to mimic oxidative stress injury. Four groups were finally divided: control group; H2O2 group; H2O2 + Tan IIA group; H2O2 + Tan IIA + G15 group. Results In present study, we demonstrate data indicating that a significant increase in the superoxide dismutase (SOD) activity and a decrease in the reactive oxygen species (ROS) content were observed in the kidneys and renal cells preserved with Tan IIA compared with those preserved with the Celsior solution alone after 24 h and 48 h of hypothermic preservation (P < 0.01). The expression of phosphorylated mitogen-activated protein kinase kinase (MEK), phosphorylated extracellular signal-regulated protein kinases 1/2 (ERK1/2), phosphorylated glycogen synthase kinase-3β (GSK-3β) and cleaved caspase-3 was lower in the kidneys and renal cells preserved with Tan IIA than in those preserved with the Celsior solution alone after 24 h and 48 h of hypothermic preservation (P < 0.01). The mitochondrial morphology was rescued and adenosine triphophate (ATP) production and mitochondrial membrane potential were increased in the Tan IIA groups. Finally, Tan IIA also decreased cell apoptosis. Conclusion It suggests that the supplementation of the standard Celsior solution with Tan IIA may significantly improve long-term kidney preservation. Tan IIA attenuated oxidative stress injury and decreased apoptosis levels via activation of the MEK/ERK1/2/GSK-3β signaling pathway during kidney hypothermic preservation.

Keywords

• Tanshinone IIA
• Hypothermic preservation
• Celsior solution
• Reactive oxygen species
• Apoptosis