TY - JOUR AU - Lu Hong AU - Zhang Xin-yue AU - Zhou Yan-quan AU - Wen Xin AU - Zhu Li-ying PY - 2016 TI - Proteomic alterations in mouse kidney induced by andrographolide sodium bisulfite JF - Acta Pharmacologica Sinica; Vol 32, No 7 (July 2011): Acta Pharmacologica Sinica Y2 - 2016 KW - N2 - Aim: To identify the key proteins involved in the nephrotoxicity induced by andrographolide sodium bisulfite (ASB). Methods: Male ICR mice were intravenously administrated with ASB (1000 or 150 mg·kg -1 ·d -1 ) for 7 d. The level of malondialdehyde (MDA) and the specific activity of superoxide dismutase (SOD) in kidneys were measured. The renal homogenates were separated by two-dimensional electrophoresis, and the differential protein spots were identified using a matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF)/TOF mass spectrometry. Results: The high dose (1000 mg/kg) of ASB significantly increased the MDA content, but decreased the SOD activity as compared to the control mice. The proteomic analysis revealed that 6 proteins were differentially expressed in the high-dose group. Two stress-responsive proteins, ie heat shock cognate 71 kDa protein (HSC70) and peroxiredoxin-6 (PRDX6), were regulated at the expression level. The remaining 4 proteins involving in cellular energy metabolism, including isoforms of methylmalonyl-coenzyme A mutase (MUT), nucleoside diphosphate-linked moiety X motif 19 (Nudix motif19), mitochondrial NADH dehydrogenase 1 alpha subcomplex subunit 10 (NDUFA10) and nucleoside diphosphate kinase B (NDK B), were modified at the post-translational levels. Conclusion: Our findings suggest that the mitochondrion is the primary target of ASB and that ASB-induced nephrotoxicity results from oxidative stress mediated by superoxide produced by complex I. UR - http://www.chinaphar.com/article/view/7318