Effects of fluoride on growth and development, learning and memory, and oxidative stress in serum of offspring rats / 中华地方病学杂志

ABSTRACT

Objective:To observe the change of growth and development, learning and memory, and oxidative stress in serum of offspring rats with fluorosis, and to explore the mechanism of fluoride on neurobehavioral development of offspring rats.Methods:Seventy-two SD rats (female and male ratio 3 ∶ 1) were fed adaptively for one week. According to their body mass [(80 ± 20) g], they were divided into control group (drinking tap water, containing less than 0.5 mg/L fluoride), low fluorine group (drinking water containing 10.0 mg/L of fluoride), and high fluorine group (drinking water containing 100.0 mg/L of fluoride) with random number table. After six months of feeding, they mated freely and gave birth in each group (24 rats with 18 females and 6 males). The rats in each group continued to be exposed to fluoride after giving birth, and the offspring rats were exposed to fluoride through breast milk feeding until the 28th day after birth. Body and brain weight, growth and development indicators (auricle separation, eyes opening, teeth eruption and hair growth) and neurobehavioral development indicators (cliff avoidance, auditory startle, surface righting and vibrissa positioning) were recorded. On the 28th day after birth, the learning and memory abilities (escape latency) of offspring rats were tested by Morris water maze; blood samples were taken from eyeballs to detect the content of nitric oxide (NO), the activity of nitric oxide synthase (NOS) and inducible nitric oxide synthase (iNOS).Results:On the 21st day and 28th day after birth, the differences of body weight among control group, low fluorine group and high fluorine group [21st day (54.70 ± 3.02), (52.30 ± 2.58), (51.30 ± 2.71) g, 28th day (91.70 ± 5.03), (90.40 ± 4.76), (86.00 ± 4.55) g] were statistically significant ( F = 3.96, 3.70, P < 0.05); on the 21st day, the body weight of high fluorine group was lower than that of control group ( P < 0.05); on the 28th day, the body weight of the high fluorine group was lower than those of control group and low fluorine group ( P < 0.05). On the 28th day, the difference of brain weight of control group, low fluorine group and high fluorine group was statistically significant ( F = 6.19, P < 0.05); and the low fluorine group and high fluorine group were lower than that of control group ( P < 0.05). Among the growth development indicators, the difference of time of completing eyes opening in control group, low fluorine group and high fluorine group was statistically significant ( F = 3.64, P < 0.05); and the high fluorine group was higher than that of control group ( P < 0.05). In neurobehavioral development indicators, the differences of time of completing cliff avoidance, surface righting between the control group, low fluorine group and high fluorine group were statistically significant ( F = 8.29, 7.69, P < 0.05); and the time of completing cliff avoidance in high fluorine group was higher than those of control group and low fluorine group ( P < 0.05), the time of completing surface righting was higher than that of control group ( P < 0.05). In Morris water maze, on the 4th day, the escape latencies of low fluorine group and high fluorine group were higher than that of control group ( P < 0.05). The results of oxidative stress in serum showed that there were statistically significant differences in serum NO content, NOS and iNOS activitives between the control group, low fluorine group and high fluorine group ( F = 4.86, 66.48, 70.95, P < 0.05); and the NO content of the high fluoirne group was higher than that of the control group ( P < 0.05), the activities of NOS and iNOS of the high fluoirne group were higher than those of control group and the low fluorine group ( P < 0.05). Conclusion:Excessive fluoride can increase the level of oxidative stress in serum, which may be closely related to the neurobehavioral retardation and the decline of learning and memory ability of offspring rats.