An Experimental Study On The Fluoride-induced Renal Toxicity And Its Mechanisms

To probe into the fluoride-induced renal toxicity and its possible mechanisms in rats so as to provide theoretical basis for the prevention and treatment of fluorosis. A total of 32 with male and female evenly weighting 150～180g were randomly divided into 4 groups, control group with normal saline, the low fluoride group of 100 mg·kg-1·d-1 NaF, the medium fluoride group of 200 mg·kg-1·d-1 NaF and the high fluoride group of 300 mg·kg-1·d-1 NaF, with 8 rats in each group. The rats were exposed to fluoride by intragastric administration for 90 days. The weight of the rats was measured one time every 3 days. The day after the last intragastric administration, the blood samples were collected on eyes of rats and all rats were killed. The Rat kidneys were promptly plucked off and the organ coefficient of kidney was calculated. The tissues of kidney were made into pathological sections and the pathological changes of rat kidney were observed by light microscopy. Some indexes of renal function such as serum urea, serum creatinine were measured with biochemical analyzers. The levels of the five trace elements in serum of rats were measured with Atomic Absorption Spectrophotometer. One of two kidneys from each Rat was digested with HNO3-KClO4 at low temperature. Five trace elements in kidney tissue were determined by air-acetylene flame atomic absorption spectrometry, and another one kidney were prepared as homogenate to detect the content of malondialdehyde (MDA), Hydrogen peroxide (H2O2) and the activity of catalase (CAT).The results indicated that:1.There were statistic differences among groups in the weight of rats on exposure 30 days. Compared with control group, the weight of rats among three groups showed no significant difference (P>0.05). However, the weight of rats in low and medium fluoride groups after 30 days exposure was significant increased compared with high fluoride group (P<0.05), but significant differences were not observed between after 60 days and 90 days exposure.2.The organ coefficient of kidney among four groups showed no significant difference (P>0.05).3.Under the light microscopy, granular degeneration to some extent was observed in the epithelial cells of kidney proximal tubule, some cells showed vacuolar degeneration, and also mildly congestion and swelling in mesenchymal blood vessels were observed.4.The serum urea of the high fluoride group showed significant increase compared with control group (P<0.01). Meanwhile, the serum urea of the medium group and high fluoride group showed significant increase compared with the low fluoride group (P<0.05). The serum creatinine showed no difference between any each of fluoride exposure groups compared with the control group (P>0.05).5.The Cu2+ contents in rat serum of the low group and high fluoride groups showed significant decrease compared with control group (P<0.05). The Fe3+ contents in rat serum of the medium and high fluoride group showed significant decrease compared with control group (P<0.01). Meanwhile, The Fe3+ contents in rat serum of the medium fluoride group showed significant decrease compared with control group (P<0.05). Compared with the medium fluoride group, the Cu2+ contents in rat serum of high fluoride groups showed significant decrease(P<0.05). The contents of Ca2+, Mg2+ and Zn2+ in rat serum were not different in each group compared with the control group (all P>0.05).6.The Zn2+ contents in kidney tissue from the medium fluoride group showed significant decrease compared with control group (P<0.05). The Fe3+ contents in kidney of the high fluoride groups showed significant decrease compared with control group (P<0.05). The Ca2+ contents in kidney tissue of the low fluoride groups showed significant decrease compared with control group (P<0.05). Meanwhile, the Fe3+ contents in kidney of the medium and high fluoride groups showed significant decrease compared with low fluoride group (P<0.01). The Ca2+ contents in kidney tissue of the medium and high fluoride groups showed significant increase compared with low fluoride group (P<0.05). Compared with the medium fluoride group, The Zn2+ contents in kidney tissue from the medium fluoride group showed significant increase compared with medium group (P<0.05). The contents of Mg2+ and Cu2+ in kidney were not different in each group compared with the control group (all P>0.05).7.Compared with the control group, the activity of CAT in kidney tissue from the high fluoride group showed significant decrease (P<0.05). The content of MDA showed significant increase compared with the control group (P<0.05). Compared with the low group, the activity of CAT in kidney tissue from the high fluoride group showed significant decrease (P<0.05). The content of MDA showed significant increase compared with the medium group (P<0.05). The contents of H2O2 in kidney were not different in each group compared with the control group (all P>0.05).The results indicated that fluoride could cause damage to the kidney of rat. Fluoride could reduce the content of metallic elements, and cause significant change in renal tissue and lead to some disorder in redox equilibrium of kidney tissue, which might be related to its damage mechanism. However, its specific mechanism needed to further study.