Evaluation of the chronic intoxication of fluoride on human serum metabolome using untargeted metabolomics

Drinking water is the main source of fluoride intake for the human body and its regulated consumption helps in decreasing dental caries. However, excessive fluoride consumption over a prolonged time period causes fluorosis disease which adversely affects many tissues and organs of the body. This paper describes the evaluation of chronic intoxication of fluoride on human serum metabolome. The untargeted metabolomics approach using UPLC-QTOF-MS/MS is applied for metabolomic profiling, whereas the estimation of fluoride in serum samples was carried out using the ion-selective electrode (ISE). Fluoride concentration was found to be 0.16–1.25 mg/L in serum samples of 39 fluorosis patients and 0.008–0.045 mg/L in 20 healthy samples. A total of 47 metabolites were identified based on the high-resolution mass spectrometry analysis. A volcano plot was generated to discriminate features that are significantly different between the fluorosis and healthy groups at the probability of 0.05 and fold change ≥ 2. Among all identified metabolites, intensities of ten differential identified metabolites including inosine, α-linolenic acid, guanosine, octanoyl-L-carnitine, His-Trp, phytosphingosine, lauroyl-L-carnitine, hydrocortisone, deoxyinosine and dodecanedioic acid have been found altered in disease samples compared to healthy controls. Major pathways identified based on these metabolites include energy metabolism, fatty acid oxidation, purine degradation pathway, elevated protein degradation, and increased ω-6 fatty acid linoleate signatures were observed.