Kurşun Maruziyeti ve Şelasyon Tedavisi Sonrası Metabolomik ve Lipidomik Analizler

Abstract

Lead is a widely preferred heavy metal in the industry due to its useful physicochemical properties and it has important toxic effects. Chelation agents are used in its treatment and intravenous sodium calcium edta is one of the important chelation agents used in the treatment. With this thesis study, examining the changes in the metabolomic profiles before and after chelation therapy, evaluating the oxysterol levels formed by auto-oxidation; Sphingosine-1-phosphate (S1P) levels, a sphingolipid metabolite, were performed. For this purpose, 7-ketocholesterol (7-KC), 3β, 5α, 6β trihydroxy cholestane (triol) and S1P levels of oxysterol derivatives formed by autoxidation were analyzed by LC-MS/MS. Metabolomic analyzes were performed with GC-MS/MS. 7-KC and triol levels before chelation were measured as 37.35 ± 2.53 ng/ml and 41.81 ± 2.54 ng/ml while after chelation they were 22.91 ± 4.49 ng/ml and 17.64 ± 3.42 ng / ml, respectively (p <0.001). S1P levels were measured as 60.76 ± 15.03 ng/ml before chelation and 48.79 ± 10.75 ng/ml for afterwards. In addition, pathway analysis was made using the metabolites determined in the metabolomic studies. The results showed that important pathways such as aspartate, glutamate, homocysteine metabolisms, mitochondrial electron transport chain, as well as sphingolipid metabolism and linolenic and linoleic acid metabolism pathways were affected. In the experiments, it was determined that the chelation treatment reversed the increased cholesterol auto-oxidation when compared before and after chelation treatment, and S1P levels decreased with chelation application. Metabolomic analysis results were also predicted to support the targeted lipidomic analysis performed. The study has shown that lipid metabolism is affected in lead exposure and chelation therapy is effective in reversing possible damage.