To detect the expression of peroxisome proliferator-activated receptor γ (PPARγ) in the brains of rats with chronic fluorosis and elucidate the relationship between PPARγ and oxidative stress in chronic fluorosis.

According to body weight (100-120 g), sixty healthy SD rats were divided into control group(less than 0.5 mg/L fluoride in drinking water), low fluoride group (5.0 mg/L fluoride in drinking water, prepared by NaF), and high fluoride group (50.0 mg/L fluoride in drinking water) via the random number table method, 20 rats in each group (half male and half female). The experiment periods were 3 and 6 months, respectively. Then 24-hour urine samples of rats were collected from each group, all rats were put to death and brain tissues were taken. The fluoride contents in urine and brain tissue were measured with fluoride-ion selective electrode; the levels of PPARγ protein and mRNA in the cortex and hippocampus were determined by Western blotting and Real-time fluorescence quantitative PCR, respectively; and the activities of superoxide dismutase (SOD) and level of malondialdehyde (MDA) in serum were detected by xanthine oxidase method and thiobarbituric acid method; the correlation between PPARγ protein expression and oxidative stress was analyzed.

After 3 and 6 months of treatment, the contents of fluoride in urine and brain in low fluoride group [(1.57 ± 0.18) mg/L, (3.43 ± 0.70) μg/g; (1.79 ± 0.17) mg/L, (7.40 ± 1.21) μg/g] were higher than those of control group [(1.11 ± 0.17) mg/L, (2.39 ± 0.50) μg/g; (1.02 ± 0.15) mg/L, (2.87 ± 0.82) μg/g, P < 0.05], and the values in high fluoride group [(1.91 ± 0.23) mg/L, (6.70 ± 0.87) μg/g; (2.44 ± 0.51) mg/L, (12.10 ± 1.30) μg/g] were significantly higher than those in low fluoride group (P < 0.05). In high fluoride group after 3 months of treatment, the expression of PPARγ protein [(79.00 ± 3.46)%, (80.35 ± 2.50)%] and mRNA [(79.11 ± 11.18)%, (82.10 ± 9.94)%] in hippocampus and cortex of rat brains were significantly lower than those of low fluoride group [(104.01 ± 5.77)%, (101.17 ± 6.35)%; (112.88 ± 22.15)%, (101.14 ± 8.60)%, P < 0.05]; the expression of PPARγ protein [(64.32 ± 10.43)%, (60.20 ± 10.92)%] and mRNA [(41.03 ± 9.93)%, (52.25 ± 11.48)%] in the same brain regions of the rats after 6 months of treatment in high fluoride group were significantly lower than those of control group [(99.99 ± 11.19)%, (100.00 ± 11.30)%; (100.00 ± 10.00)%, (100.00 ± 9.00)%] and low fluoride group [(73.88 ± 3.36)%, (81.50 ± 14.90)%; (76.02 ± 8.65)%, (73.36 ± 7.43)%, P < 0.05]. The activities of SOD in serum in low and high fluoride groups after 6 month treatment [(37.94 ± 1.92), (35.54 ± 2.53) U/ml] were significantly lower than that of control group [(41.24 ± 0.66) U/ml, P < 0.05], and the value in high fluoride group was lower than that in low fluoride group (P < 0.05); serum MDA contents in high fluoride group after 3 and 6 month treatment [(8.29 ± 1.49), (11.63 ± 1.04) nmol/mg pr] were higher than those in low fluoride group [(6.39 ± 0.69), (7.50 ± 1.64) nmol/mg pr] and control group [(5.02 ± 0.71), (5.87 ± 1.03) nmol/mg pr, P < 0.05]. The correlation analysis results showed the levels of PPARγ protein in hippocampus and cortex of rats were negatively correlated with fluoride contents in brain tissues (3 month: r=- 0.769, - 0.793; 6 month: r=- 0.832, - 0.870; P < 0.05), positively correlated with SOD activities (3 month: r=0.550, 0.826; 6 month: r=0.822, 0.896; P < 0.05) and negatively correlated with MDA contents (3 month: r=- 0.703, - 0.609, 6 month: r=- 0.792, - 0.657; P < 0.05) in serum.

Declined expression of PPARγ at protein and mRNA levels has been detected in brains of rats with chronic fluorosis, which might be related to the increase of oxidative stress. PPARγ may be involved in the occurrence of chronic fluorosis.

Fluoride; Brain; Peroxisome proliferator-activated receptor γ; Superoxide dismutase; Malondialdehyde; Rats