Effects of Fluoride on Submandibular Glands of Mice: Changes in Oxidative Biochemistry, Proteomic Profile, and Genotoxicity

Abstract

Although fluoride (F) is well-known to prevent dental caries, changes in cell processes in different tissues have been associated with its excessive exposure. Thus, this study aimed to evaluate the effects of F exposure on biochemical, proteomic, and genotoxic parameters of submandibular glands. Twenty one old rats (n = 30) were allocated into three groups: 60 days administration of drinking water containing 10 mgF/L, 50 mgF/L, or only deionized water (control). The submandibular glands were collected for oxidative biochemistry, protein expression profile, and genotoxic potential analyses. The results showed that both F concentrations increased the levels of thiobarbituric acid–reactive substances (TBARS) and reduced glutathione (GSH) and changed the proteomic profile, mainly regarding the cytoskeleton and cellular activity. Only the exposure to 50 mgF/L induced significant changes in DNA integrity. These findings reinforce the importance of continuous monitoring of F concentration in drinking water and the need for strategies to minimize F intake from other sources to obtain maximum preventive/therapeutic effects and avoid potential adverse effects.

Maternal Fluoride Exposure Exerts Different Toxicity Patterns in Parotid and Submandibular Glands of Offspring Rats

“…In previous studies, F exposure was shown to cause damage to the major salivary glands of adult animals [17,18]. In the present study, on the other hand, maternal exposure to F led to subtler changes than those in adult animals [17,18].…”

“…In previous studies, F exposure was shown to cause damage to the major salivary glands of adult animals [17,18]. In the present study, on the other hand, maternal exposure to F led to subtler changes than those in adult animals [17,18]. This suggests that the damage to salivary glands may be related to the form of exposure, (i.e., directly from the diet or indirectly through placenta/breastfeeding) and time of exposure, (i.e., initial vs. later stages of development), which may account for the lower susceptibility to damage in offspring compared to exposed adult organisms [24].…”

“…When considering the indirect exposure protocol and blood plasma F levels in offspring, oxidative biochemical changes triggered by the concentrations used in this study could be expected, even if more subtly, since previous studies in adult animals with direct exposure have shown that these same concentrations can modulate molecular and biochemical aspects of salivary glands for a longer time [17,18]. In this regard, evidence shows that increased bioavailability of F in blood plasma may be associated with an imbalance in the redox system caused by F, which can be considered the key mechanism for these changes [27].…”

“…Concerning the oral cavity, the chronic ingestion of above-optimum F concentrations can lead to dental fluorosis development [16]. Other structures can also be affected by exposure to F at high concentrations, such as salivary glands [17,18]. These are important organs for maintaining homeostasis in the oral environment, given that saliva (their main product) performs clearance, buffering, remineralization of dental enamel, and lubrication, in addition to aiding in speech and swallowing [19][20][21][22].…”

“…Previous studies using an adult animal model were able to associate long-term F exposure with several alterations in the parameters of oxidative biochemistry and proteomic profile pattern of the major salivary glands [17,18]. However, evidence on the effects of indirect exposure to F during gestation and lactation and on the possible repercussions on the major salivary glands of the offspring is still lacking.…”