Epidemiological studies conducted in the areas with high levels of naturally fluoridated water shows increase in birth defects placing fluoride into the same category as toxic metals like lead, mercury, methyl mercury etc. (Guth et al., 2020). Exposure to high fluoride concentration in drinking water during in utero development may result in skeletal fluorosis which becomes evident in childhood. Adverse effects on reproduction have been reported in animals exposed to 100 ppm or greater concentrations of fluoride in their diet or through drinking water. Number of previously reported animal studies suggest that exposure to low concentrations of fluoride do not result in impaired fertility and reproductive capabilities. The present study is an effort to give reason to and correlate the findings obtained through experiments with the various mechanisms by which Sodium fluoride reaches the tissues of the body and influences the normal physiological function of the body; thereby causing developmental defects during the pregnancy period. The study also attempts to find the possible reason / mechanism for averting the teratogenic effect of fluoride by using Aloe vera gel which is taken as a supplement during the early development of a fetus
It has been reported that Sodium fluoride and other Soluble fluorides in groundwater are absorbed from the gastrointestinal tract into the blood (Barbier et al. 2010; EFSA 2005), attaining the peak plasma levels within 20–60 min after oral ingestion (EFSA2005; Whitford et al. 2008). Fluorides is also able to cross biological membranes by diffusion as the non-ionic hydrogen fluoride (HF) (Gutknecht and Walter 1981) and remains retained in tissues for a significant period of time. The largest amount of absorbed fluoride is retained in bone and teeth, where about 99% of the total fluoride is detected (Ekstrand et al. 1977). Animal studies have reported that fluoride crosses the placenta and gets incorporated in fetal issues; increasing its concentration in fetal blood two folds. Fetus is not protected against fluoride that circulates in the maternal blood. The study further reports that fluoride gets transferred to the infant through mother’s milk. Thus, the fetus and new born pups are much vulnerable to fluoride (Caldera et al. 1988; Shen and Taves1974). The skeletal deformities and other morphometric changes observed in the present study can be explained on the basis of such above mentioned findings (Guth et al., 2020). Not only this, fluoride also interacts with proteins, particularly enzymes, and usually inhibits/ stimulates enzyme activity at the concentrations in the millimolar range (Barbier et al. 2010; Mendoza-Schulz et al. 2009) thereby disrupting normal physiology of the body. Fluoride hampers cell functions through generation of superoxide anions (Garcia- Montalvo et al.2009; Izquierdo-Vega et al. 2008); mitochondrial toxicity, e.g., opening of the transition pore (Anuradha et al. 2001); release of cytochrome c from mitochondria and induction of apoptosis (Chlubek et al. 2003; Lee et al. 2008).
The previous study also suggest that by interfering with calcium metabolism and enzyme mechanisms, fluorides act as direct cell poisons (Guth et al., 2020). It has also been reported that Fluoride interacts with hydrochloric acid in the stomach to form a powerful corrosive hydrofluoric acid. Fluoride ions also combine with serum cations after absorption, especially calcium and magnesium leading to hypocalcaemia and hypomagnesaemia. (Narayanswami et al., 2010). Bones are more susceptible to its effect primarily because fluoride replaces hydroxides and itself gets deposited in bones. The chronic effects of which are called Fluorosis of the skeleton. These findings can be correlated with the finding of Brittany et al., 2014, in which people have developed bone related problems, in those geographical areas where Fluoride concentration is high. The high accumulation of NaF in brain tissues after passing through placenta and mother’s milk to its newborns has also been reported (Sun et al., 2018) affecting the prenatal and postnatal development of mice. These effects were more significant following exposure to a high concentration of 300ppm of NaF causing teratogenic effects which got reduced by taking nutritive plant products like Quinoa during the whole experimental period (Choudhary and Mathur, 2020). Several authors reviewed a dose dependent relationship between NaF exposure and embryonic growth retardation in mice and have suggested protective effects of vitamins and antioxidants to ameliorate these teratogenic effects besides cautioning against excessive intake of Fluoride in the drinking water .
Acemannan, an acetylated glucomannan that makes up the major active component of the mucilaginous Aloe vera possess multifunctional properties and therefore acts as a bioactive molecule, exerting an immunostimulatory effect by activating macrophages, (Callaghan et al., 2012) and possessing wound healing actions. (Osefo et al., 2009, Hull and Beale, 1985). It also stimulates fibroblast proliferation, (Lee et al., 2017) tissue regeneration (Rauws et al, 1990) and bone marrow stromal cell proliferation and differentiation in vitro. (Hull and Beale, 1985). Thus, it is an interesting preventive agent for tissue repair. Aloe vera sap has also been found to have favorable effects on estrogen synthesis due to its phytoestrogen components such as beta sitosterol that can increase the estrogen level, thus bringing hormones to support normal development of fetus (Atik et al., 2019). More detailed studies are required to validate and explain the action mechanism of acemannan in bone building. .
It is also an established fact that nutritional supplements such as vitamins and antioxidants prevent the toxicity that is induced by fluoride because these supplements reduce the oxidative stress, decreases the lipid peroxidation, and augments the activity of antioxidant enzymes. (Elshama et al., 2018). One of the strategies to protect the body from oxidative injury and to prevent from many disorders is to increase the levels of antioxidant enzymes by increasing the dietary intake of supplements rich in antioxidant enzymes (Godoy et al., 2018). Aloe vera has very strong antioxidant nutrients. Glutathione peroxide activity, superoxide dismutase enzymes, and a phenolic antioxidant have been reported to be present in Aloe vera gel, which may be responsible for these antioxidant effects (Atik et al, 2019). Aloe vera also has unique ability to improve the absorption of natural antioxidants like vitamin C and vitamin E that in turn enhances antioxidant status to alleviate fluoride induced ROS (Vinson et al., 2005).Vitamin E which is an essential component of Aloe vera must have exerted antioxidant effects by scavenging lipid peroxyl radicals that are free radicals in vivo as well as in vitro (Niki, 2014). Ayurveda also mentions that Aloe-vera can been taken as a Naimittika Rasayanas during pregnancy; because, it being rich in nutritional contents and iron supplements that are very essential to promote the health of the pregnant women and facilitates full growth and development of progeny in the womb (Shastry,1999; Singh, 2000).
The findings in the present study suggest the multifaceted qualities of Aloe vera. The present study also suggests marked efficacy of Aloe vera in reducing fluoride induced teratogenic effects. However, still more detailed studies are required using variable doses of Aloe vera post flouride exposure