Serum Concentration of Fluoride in Patients with Alcoholic Liver Cirrhosis from the Lublin Region in Eastern Poland

Prystupa, Andrzej; Sak, Jarosław; Kiciński, Paweł; Stenzel-Bembenek, Agnieszka; Błażewicz, Anna

doi:10.3390/ijerph18031115

Cited by 5 publications

(1 citation statement)

References 36 publications

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“…Previous study showed that fluorosis could accelerate hepatic oxidative stress in animals, and the mechanism may be related to fluoride-induced hepatocyte apoptosis and autophagy ( 39 – 41 ). In addition, a correlation between the stage of patients with alcoholic cirrhosis and serum fluoride levels was confirmed, with elevated plasma fluoride accompanied by raised alanine aminotransferase and total bilirubin ( 42 ). In a recent population-based cross-sectional study, by monitoring fluoride concentrations in plasma and household tap water, as well as evaluating the hepatic parameters in serum, it was found that every 1 mg/mL increase in water fluoride strongly correlated with 0.93 mg/dL decreased blood urea nitrogen concentration ( 43 ).…”

Section: Discussionmentioning

confidence: 90%

Fluorine impairs carboxylesterase 1-mediated hydrolysis of T-2 toxin and increases its chondrocyte toxicity

et al. 2022

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BackgroundT-2 toxin is recognized as one of the high-risk environmental factors for etiology and pathogenesis of Kashin-Beck disease (KBD). Previous evidence indicates decreased serum fluorine level in KBD patients. However, whether fluoride could regulate carboxylesterase 1 (CES1)-mediated T-2 toxin hydrolysis and alter its chondrocyte toxicity remains largely unknown.MethodsIn this study, in vitro hydrolytic kinetics were explored using recombinant human CES1. HPLC-MS/MS was used to quantitative determination of hydrolytic metabolites of T-2 toxin. HepG2 cells were treated with different concentration of sodium fluoride (NaF). qRT-PCR and western blot analysis were used to compare the mRNA and protein expression levels of CES1. C28/I2 cells were treated with T-2 toxin, HT-2 toxin, and neosolaniol (NEO), and then cell viability was determined by MTT assay, cell apoptosis was determined by Annexin V-FITC/PI, Hoechst 33258 staining, and cleaved caspase-3, and cell cycle was monitored by flow cytometry assay, CKD4 and CDK6.ResultsWe identified that recombinant human CES1 was involved in T-2 toxin hydrolysis to generate HT-2 toxin, but not NEO, and NaF repressed the formation of HT-2 toxin. Both mRNA and protein expression of CES1 were significantly down-regulated in a dose-dependent manner after NaF treatment in HepG2 cells. Moreover, we evaluated the chondrocyte toxicity of T-2 toxin and its hydrolytic metabolites. Results showed that T-2 toxin induced strongest cell apoptosis, followed by HT-2 toxin and NEO. The decreased the proportion of cells in G0/G1 phase was observed with the descending order of T-2 toxin, HT-2 toxin, and NEO.ConclusionsThis study reveals that CES1 is responsible for the hydrolysis of T-2 toxin, and that fluoride impairs CES1-mediated T-2 toxin detoxification to increase its chondrocyte toxicity. This study provides novel insight into understanding the relationship between fluoride and T-2 toxin in the etiology of KBD.

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