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 ultra-high performance liquid chromatography tandem mass spectrometry analysis was used to analyze the collected serum sample. Data were analyzed using principal component analysis, partial least squares-discriminate analysis, and orthogonal partial least squares-discriminant analysis. All potential metabolites were identified by comparing with human metabolome database, Metlin database, lipid maps, and chemspider database. Results Eleven 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, and 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.

Screening and identification of potential key biomarkers for glucocorticoid-induced osteonecrosis of the femoral head

“…It was confirmed in previous studies that steroid use may result in changes in the lipid metabolism, which increase the risk of fat embolism[ 18 , 19 ]. Our team's studies also confirmed that GIONFH is closely related to the pathogenesis of lipid metabolism disorder induced by high-dose hormone in vivo[ 20 – 22 ]. Therefore, in order to further confirm the association between the onset of GIONFH and lipid metabolism disorder, a hypolipidemic drug group was added as comparative research to the Glucocorticoid-induced femoral head necrosis model rabbits in the animal experiment of this study.…”

Preparation of low molecular weight polysaccharides from Tremella fuciformis by ultrasonic-assisted H2O2-Vc method: Structural characteristics, in vivo antioxidant activity and stress resistance

“…Lv et al (2022) found that the complex of Ganoderma lucidum polysaccharides and chromium had a significant impact on the regulation of glucose and lipid metabolism in high-fat and high-sugar diet rats, which was significantly influenced by the alpha linolenic acid metabolism pathway [69] . Besides, it was found that there existed a close correlation between alpha linolenic acid metabolism disorder and hyperuricemia and bone necrosis [70] , [71] . Pantothenate and CoA biosynthesis metabolic pathways were found that it had a close relationship with diabetes, nephropathy and iron deficiency anemia [72] , [73] , [74] .…”

Integrated proteomics and metabolomics analysis of sclerosis-related proteins and femoral head necrosis following internal fixation of femoral neck fractures

“…These findings highlight the crucial role glycerophospholipid metabolism plays in preserving skeletal integrity 45 . In the context of femoral head osteonecrosis, metabolomic investigations have pinpointed glycerophospholipid metabolism as a significant pathway implicated in the disease process 46 . Statin medications have shown efficacy in treating steroid-induced ischemic necrosis of the femoral head, potentially by ameliorating dysregulated glycerophospholipid metabolism 47 , 48 .…”