Objective To explore the toxicity and mechanism of combined exposure to fluoride and arsenic on bone absorptive capacity of osteoclasts in rats.
Methods A total of 54 SD rats of clean grade were randomly divided into 9 groups, with 6 rats in each group (half males and half females). Based on a pilot experiment and literature review, the animals were treated with NaF and NaAsO2 by intragastric administration:control group (F0As0), low fluoride group (5mg/kg, F5), high fluoride group (20mg/kg, F20), low arsenic group (2.5mg/kg, As2.5), high arsenic group (10 mg/kg, As10), low fluoride and low arsenic group (5 mg/kg+2.5 mg/kg, F5As2.5), low fluoride and high arsenic group (5 mg/kg+10 mg/kg, F5As10), high fluoride and low arsenic group (20 mg/kg+2.5 mg/kg, F20As2.5), and high fluoride and high arsenic group (20 mg/kg+10 mg/kg, F20As10). The levels of tartrateresistant acid phosphatase 5b (TRACP-5b) and pyridinoline cross linked carboxyterminal telopeptide of type Ⅰ collagen (ICTP) in rat serum, as well as the levels of osteoprotegerin (OPG), prostaglandin (PGE2), and 1, 25-dihydroxy vitamin D31, 25(OH)2D3 in homogenate supernatant of right femur tissue samples were determined by ELISA.
Results The expression levels of ICTP and TRACP-5b in the high fluoride group were higher than those in the control group (F0As0:1.352±0.025, 2.942±0.078; F20:1.427±0.026, 3.202±0.142; Ps < 0.05), while there was no significant difference between any individual arsenic exposure group and the control group (Ps>0.05). The expression levels of ICTP and TRACP-5b in the high fluoride and high arsenic group were lower than those in the high fluoride and low arsenic group (F20As2.5:1.442±0.034, 3.280±0.095; F20As10:1.345±0.042, 3.053±0.084; Ps < 0.05). The results of partial correlation analysis and interaction analysis showed that the expression levels of TRACP-5b and ICTP were positively correlated with fluoride concentration (partial correlation coefficient:0.663, 0.392; Ps < 0.05), and fluoride showed the main effect (F=24.560, 8.188; Ps < 0.05). The expression levels of OPG, PGE2, and 1, 25(OH)2D3 in the groups treated with high doses of fluoride were significantly higher than those in the control group (F0As0:12.278±0.220, 1.352±0.025, 9.582±0.363; F20:14.087±0.797, 1.427±0.026, 11.915±0.931; Ps < 0.05). The expression level of PGE2 in the low fluoride and high arsenic group was lower than that in the low fluoride and low arsenic group (F5As2.5:1.442±0.034; F5As10:1.345±0.080; P < 0.05). The expression level of 1, 25(OH)2D3 in the high fluoride and high arsenic group was lower than that in the high fluoride and low arsenic group (F20As2.5:12.082±0.860; F20As10:10.567±0.695; Ps < 0.05). The results of partial correlation analysis and interaction analysis showed that the expression levels of OPG, PGE2, and 1, 25(OH)2D3 were positively correlated with fluoride concentration (partial correlation coefficient:0.804, 0.487, 0.748; Ps < 0.05), and fluoride showed as the main effect (F=47.100, 9.031, 3.114; Ps < 0.05); the direct toxic effects of arsenic on OPG, PGE2, and 1, 25(OH)2D3 were minor (P>0.05).
Conclusion Arsenic can inhibit the auxo-action of fluorine on the bone absorption of osteoclasts in rats, and the fluorine-arsenic interaction is mainly antagonistic. PGE2 and 1, 25(OH)2D3 may be important factors in the regulation of osteoclast bone absorption function.
DownLoad: