… In our study higher serum fluoride concentrations were associated with changes in liver related parameters. In all Pugh-Child score groups of analyzed patients with different stages of alcoholic liver cirrhosis, elevated levels of plasma fluoride, increased activities of both hepatic aminotransferases, ALT and AST, and total bilirubin concentration were shown. The risk of serious complications like esophageal varices, ascites and encephalopathy was highest in the most advanced stage of cirrhosis (P-Ch C), which determines that these two toxic agents, alcohol and fluoride, might act synergistically in the liver damage process. The time of alcohol consumption in this group was also the longest.

Blood fluoride content (serum fluoride level) can reflect the external environmental exposure level of an organism to this element. In our study all patients (control and study groups) were from the Eastern region of Poland where the drinking water fluoride concentration range was below 0.5 mg/L (below 500 ppb) in the period January 2018–December 2019, according to information given by the Municipal Water and Sewerage Company in Lublin (MPWiK) responsible for communal water distribution in the region [14]. However, when designing nationwide population biobanking for scientific studies, the possibility of the common determination of heavy metals and fluoride in the serum of biobank’s blood donors should be considered as a reliable assessment of environmental exposure [29,30].

Taves indicated that the average serum fluoride concentration of sixteen individuals was 0.013 ppm (13 ppb) [31]. In our study, this level was 0.0255 ± 0.0177 ppm (25.5 ± 17.7 ppb) in the control group. According to Singer and Armstrong there was plasma fluoride content within the range 0.14–0.26 ppm (140–260 ppb) [32]. They conducted their research in three American States (Minnesota, Michigan, South Dakota) in the period 1958–1959 where fluoride levels in water were in the range from 0.15 to 5.4 ppm (150–5400 ppb). The highest fluoride level was observed among individuals from Lake Preston (South Dakota)—0.26 ± 0.0124 ppm (260 ± 12.4 ppb), where the fluoride level of communal showed the highest level at 5.4 ppm (5400 ppb) [32]. It is worth noticing that the average plasma fluoride level which observed in Singer and Armstrong’s study in this American region was ten times higher than the average level in our study’s control group. However, the level of fluoride in communal water in Lake Preston fifty years ago was also more than ten times higher than the municipal water that patients drank in the Lublin region in 2018–2019 [14].

The main source of fluoride is water. However, it can be found in other beverages and foods. Alcoholic beverages can be an important source of fluoride, especially in the group of ALD patients. Paz et al. identified the fluoride concentration of 53 samples of organic and non-organic wines (the Canary Islands and mainland Spain) within the range of 0.03 to 0.70 mg/L [33]. In a previous study, two decades earlier, Martinez et al. stated that the mean concentration of fluoride in 70 samples of wine (the Canary Islands) from a region with a high concentration of fluoride in drinking water was significantly higher than the mean concentration in other samples [34]. In the Lublin region, beer is consumed much more often than wine. Therefore, the research carried out by Styburski et al. was important [35]. They compared the fluoride concentration in different beer samples: Thailand (0.260 ppm), Italy (0.238 ppm), Mexico (0.210 ppm), China (0.203 ppm) and Polish beers (0.089 ppm). Goschorska et al. compared the fluoride concentration in 48 types of drink with low, medium, and high alcohol content available in Poland, both Polish and foreign [36]. They stated that the highest fluoride levels were determined in beers and wines, while the lowest levels were identified in vodkas.

The production of ethanol oxidation-acetaldehyde can enhance free-radical damage by binding to glutathione and other free-radical defense enzymes in liver tissue. Fluoride is also known to destroy biomolecules through generation of reactive oxygen species (ROS) and to augment the oxidative stress condition due to inhibition or interaction with antioxidative enzymes which makes the liver tissue more susceptible to biochemical injury by other toxicant molecules [37].

Recent evidence has reported that fluoride can also augment the oxidative stress condition in kidneys by increasing the concentration of ROS in kidney tissue with decreased levels of glutathione (GSH), accompanied by decreased GST activity in kidney tissue [37]. Once again, the imbalanced pro-oxidant/antioxidant status, leading to the generation of oxidative stress conditions, is shown as a result of fluoride toxicity. The results suggest that higher circulating fluoride levels are the results of liver dysfunction. However, it would be worth assessing the content of fluoride in liver biopsies in further research.

Our study has some limitations: a small number of subjects and voluntary selection, difficulties in assessing actual renal function, no assessment of fluoride concentration in liver bioptates and omitting, in the protocol of our study, the consumption of alcoholic beverages (amount and type of drink).

However, this is the first attempt to assess the relationship between serum concentration of fluoride and the stages in alcoholic liver cirrhosis. We tried to show that higher serum fluoride concentrations are associated with changes in liver related parameters and stages of cirrhosis. This study contributes to further research, e.g., observational, multi-center studies on the relationship between serum concentration of fluoride and the development of ALD and the consumption of alcoholic beverages. We also suggest the need of experimental studies to elucidate the molecular mechanisms of fluoride during ALD.