Untargeted metabolomics reveals the effect of lovastatin on steroid-induced necrosis of the femoral head in rabbits

Abstract

PURPOSE Lovastatin is an important medicine and it shows a significant effect against glucocorticoid-induced necrosis of the femoral head. This study aimed to investigate the effect of lovastatin on preventing necrosis of the femoral head of by serum metabolomics strategy. METHODS Adult healthy adult Japanese white rabbits were divided into three groups: control group, model group and drug group. The pathologic changes of femoral head were assessed with magnetic resonance imaging and microscope. Metabolomics based on UHPLC-MS/MS was used to analyze the collected serum sample. Data were analyzed using principal component analysis (PCA), partial least squares-discriminate analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). All potential metabolites were identified by comparing with HMDB database, metlin database, lipid maps and chemspider database. RESULTS 11 potential biomarkers were noted and identified as potential biomarkers. The change of biomarkers suggested that lovastatin on preventing necrosis of the femoral head may affect glycerophospholipid metabolism, linoleic acid metabolism, sphingolipid metabolism, alpha-Linolenic acid metabolism, pyrimidine metabolism, arachidonic acid metabolism. CONCLUSION The study suggested that lovastatin could prevent the glucocorticoid-induced necrosis of the femoral head of rabbits. The possible reasons were closely associated with adjusting the lipid metabolism, inhibiting adipogenesis and delaying the osteocyte apoptosis.