Proteomic alterations in mouse kidney induced by andrographolide sodium bisulfite.

aimTo identify the key proteins involved in the nephrotoxicity induced by andrographolide sodium bisulfite (ASB).

methodsMale 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.

resultsThe 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.

conclusionOur 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.