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

Abstract

There is currently a controversial and heated debate about the safety and ethical aspects of fluoride (F) used for human consumption. Thus, this study assessed the effects of prenatal and postnatal F exposure of rats on the salivary glands of their offspring. Pregnant rats were exposed to 0, 10, or 50 mg F/L from the drinking water, from the first day of gestation until offspring weaning (42 days). The offspring rats were euthanized for the collection of the parotid (PA) and submandibular (SM) glands, to assess the oxidative biochemistry and to perform morphometric and immunohistochemical analyses. F exposure was associated with a decrease in the antioxidant competence of PA in the 10 mg F/L group, contrasting with the increase observed in the 50 mg F/L group. On the other hand, the antioxidant competence of the SM glands was decreased at both concentrations. Moreover, both 10 and 50 mg F/L groups showed lower anti-α-smooth muscle actin immunostaining area in SM, while exposure to 50 mg F/L was associated with changes in gland morphometry by increasing the duct area in both glands. These findings demonstrate a greater susceptibility of the SM glands of the offspring to F at high concentration in comparison to PA, reinforcing the need to adhere to the optimum F levels recommended by the regulatory agencies. Such findings must be interpreted with caution, especially considering their translational meaning.

Atrophy and Inflammatory Changes in Salivary Glands Induced by Oxidative Stress after Exposure to Drugs and Other Chemical Substances: A Systematic Review

“…Out of 1756 articles, 26 articles regarding the effect of different substances on salivary glands were included in the analysis ( Figure 1 ). Their distribution was: 6 articles on the effect of chemotherapy drugs on salivary glands [ 5 , 12 , 15 , 16 , 18 , 19 ]; 4 articles on the effect of ethanol on salivary glands [ 6 , 7 , 9 , 20 ]; 9 articles on the effects of heavy metals on salivary glands [ 2 , 11 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]; 3 articles on the effect of fluoride on salivary gland [ 4 , 10 , 28 ]; 4 articles on the effect of other substances, such as atrazine [ 29 ], high protein diet [ 8 ], hyperoxia [ 30 ], and sodium nitrite [ 31 ]; All included studies were case-control studies. The two types of laboratory animals used were rats and mice.…”

“…Following our research, we found three articles ( Table 5 ) regarding the effects induced by fluoride on salivary glands [ 4 , 10 , 28 ]: one of them evaluated both histopathological and biochemical parameters [ 10 ] while two of them studied only the biochemical changes [ 4 , 28 ]. A study has analyzed the oxidative and antioxidative biochemical markers, both in plasma and tissue homogenate, after the administration of a high-protein diet.…”

“…Fluoride, administered in pregnant Wistar rats in doses of 10 mg/L in drinking water, decreased TEAC both in the PG and SMG of offspring while a dose of 50 mg/L in drinking water increased TEAC in the PG of offspring and decreased TEAC in the SMG of offspring. The morphological examination and CK18 immunostaining showed no differences between offspring groups regarding the parenchymal and stromal areas but the exposure to higher fluoride concentration increased the ductal area in both glands [ 10 ]. Thus, higher doses of fluoride in pregnant Wistar rats induced higher total antioxidant capacity in the PG of offspring and lower antioxidant capacity in the SMG of offspring [ 10 ].…”

“…The activities of key enzymatic antioxidants of the antioxidant system, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), are very low in saliva, compared to the same parameters measured in blood [ 5 ]. On the other hand, it was reported that the metabolism of parotid glands (PG) is essentially aerobic and is better protected against oxidative stress, while that of submandibular glands (SMG) is mainly anaerobic and therefore need less oxygen [ 4 , 6 , 7 , 8 , 9 , 10 ].…”

“…6 articles on the effect of chemotherapy drugs on salivary glands [5,12,15,16,18,19]; • 4 articles on the effect of ethanol on salivary glands [6,7,9,20]; • 9 articles on the effects of heavy metals on salivary glands [2,11,[21][22][23][24][25][26][27]; • 3 articles on the effect of fluoride on salivary gland [4,10,28]; • 4 articles on the effect of other substances, such as atrazine [29], high protein diet [8], hyperoxia [30], and sodium nitrite [31];…”