Effect of high-dose fluoride on antioxidant enzyme activities of amniotic Fluid in rats

Abstract 

Objective: To investigate the effect of high-dose fluoride on antioxidant enzyme activities of amniotic fluid and fluoride of serum in rats. 

....................Excessive intake of fluoride for a prolonged period can produce injurious effects on the teeth, skeleton and soft tissues such as the brain, thyroid, liver, kidney and reproductive organs. In recent years, various authors have investingated the relationship between fluoride toxicities and fluoride-induced OS in people15 and animals.4,5,16-21
A study22 compared foetal growth of rats that were given 40ppm fluoride with potable water on the 20th day of pregnancy with a control group and it was seen that there was a significant decrease in body weight and length. In our study, the decreased body weight of foetuses observed in the experimental group compared to the controls also indicated loss of weight due to excessive breakdown of tissue proteins.
In the current study, the serum fluoride level was found to have increased significantly in the study group compared to the control group. These results also show compatibility with an earlier study19 that showed that high levels of fluoride caused increases in serum amniotic fluid fluoride levels.
Reduced glutathione (GSH) is known to protect the cellular system against the toxic effects of lipid peroxidation as a co-substrate for glutathione peroxidase (GPx) activity.19 The depletion in the activity of GPx may result in the involvement of deleterious oxidative changes due to the accumulation of oxidative toxic products. SOD is an important defence enzyme, which converts superoxideradicals to hydrogenperoxide.20 CAT decomposes hydrogen peroxide and protects the tissues from highly reactive hydroxyl radicals.21 The reduction in the activity of these enzymes may be due to OS exerted by fluoride in toxication.
Many studies also indicate that fluoride toxicity can induce free radical toxicity in humans and animals.22-24 Fluoride has been demonstrated in vivo and in vitro to cause increased lipid peroxidation in erythrocytes of humans and in blood and tissues of experimental animals.25
In 2004, a study in which experimental rats were orally treated with 25ppm of fluoride/rat/day for 8 and 16 weeks, respectively, revealed an increase in the level of lipid peroxides along with a concomitant decrease in the activities of SOD, CAT, GSH-Px, and reduced glutathione content was observed in high-dose fluorinated groups of rats.3
In our study, a marked increase in the levels of TBARS was observed in amniotic fluid of high-dose fluorinated rats. Increased lipid peroxidation in the amniotic fluid can be due to increased OS in the cells as a result of depletion of the antioxidants cavenger system.
A recent study17 determined that in rats that were given 50ppm fluoride with potable water for a week, SOD and GSH-Px, which are from plasma antioxidant enzyme system, activity levels decreased and TBARS levels increased significantly.
In our study, the amniotic fluid of rats were used instead of 10 mg/kg/b.w./day. NaF exposed the serum of rats. To the best of our knowledge, ours is the first experimental study on the effects of high-dose NaF on antioxidant enzyme activities and TBARS levels in amniotic fluid of rats. Since high-dose NaF has passed to the placenta, excess amounts of superoxide radical (O2*-) formed in the environment, SOD, GSH-Px and CAT antioxidant enzymes that catalysed superoxide radicals (O2*-) in amniotic fluid were inhibited, and TBARS levels, which show lipid peroxidation increase, rose.
Our study has a limitation. Fluoride crosses the placenta of humans and animals and is absorbed by the foetus.26 Thus, maternal supplementation during pregnancy results in increased fluoride concentrations not only in maternal blood, but also in cord blood and offspring tissues, especially bones and teeth.27 We didn't investigate fluoride levels in amniotic fluid and infant blood because of inadequate equipment.


Conclusion

Oxidative stress induced by fluoride played an important role in the pathogenesis of fluorosis that may result in tissue damage and other secondary complications.