Fluoride causing abnormally elevated serum nitric oxide levels in chicks
Introduction
It is evidently shown that at present fluorosis is still in its prevalence around the world. Endemic fluorosis, which impairs severely the health of humans and animals, is one of the diseases caused by biogeochemical factors. China is one of the countries where the endemic fluorosis is most seriously affected. There are nearly 70 000 000 patients with fluorosis in China now. The fluorosis of human beings is mainly caused by drinking water, burning coal and drinking tea while that of animals is mainly by drinking water and supplementing feed additives such as calcium monohydrogen phosphate containing high levels of fluoride.
It is very important to prevent and cure endemic fluorosis. However, the prophylactico-therapeutic measures are mainly based on the mechanism of fluorosis. Sufficient evidence has demonstrated that fluoride produces deleterious effects in skeletal, dental and soft tissues. There are many documents concerned with the mechanism of bone and dental fluorosis. But it is still not clear of how fluoride interferes with soft tissues, such as, the thyroid gland. However, some of the following viewpoints may be very helpful for us to understand the mechanism of fluorosis in soft tissues. Firstly, many studies have shown that fluoride can induce excessive production of oxygen free radicals (Shiells and Falk, 1992), and cause the decrease in biological activities of some substances, such as catalase (CAT), superoxide dismutase (SOD), xanthine oxidase (XOD), and glutathione peroxidase (GSH-Px) which play important roles in anti-oxidation and eliminating free radicals (Guan and Yang, 1990, Zhang and Ji, 1996). Secondly, fluoride can also disturb the metabolism of proteins. It is evidently indicated that fluoride can impair the activities of a series of enzymes such as alkaline phosphatase, cholinesterase, adenylate cyclase. Thirdly, fluoride can interfere with the metabolism of carbohydrate, lipid and nuclear acids, injure immune system, and damage the parts of the body.
Our previous study has shown that fluoride can result in thyroid enlargement and severe impairment of the thyroid ultrastructure (Liu et al., 2001, Liu et al., 2002). When we tried to explain the mechanism of fluoride damaging thyroid, we found a paper reported that nitric oxide (NO) plays an important role in regulating the activities of the thyroid peroxidase (TPO) and the metabolism of thyroid hormone (Millatt et al., 1998). It was reported that fluoride can cause the changes of the activities of NOS in the brain (Xu et al., 1999). So we can obtain some elicitations from the above evidence that fluoride can cause abnormal metabolism of oxygen free radicals and NO. It is very important for us to clarify the mechanism of fluorosis in soft tissues by investigating the effect of fluoride on the metabolism of NO, anti-oxidant enzymes and lipid peroxide (LPO).
The objectives of the present study are to disclose the mechanism of fluorosis in soft tissues by studying the effect of fluoride on the levels of NO and metabolism of anti-oxidant enzymes and LPO, and to investigate how fluoride affects these indexes and what correlation there is between fluoride and these indexes.
Section snippets
Materials and methods
One-day-old Lohmann male and female chicks were chosen. The reason chicks were used as experimental animals in the test is that although previous investigations showed that poultry has more tolerance than mammalian subjects, the chronic fluorosis of chicks is very serious and leads to great economic losses due to the supplement of calcium monohydrogen phosphate which is used as a feed additive for chicks without being defluorided and therefore contains high levels of fluoride (average level of
Results
We did not find the death of chicks was caused by other infectious or nutritional factors except fluorosis. The control group showed no abnormality during the whole experimental period. Lassitude, anorexia was manifested in group 2 on the 50th day while hyponoia, gathering, and anorexia occurred in group 3 from the 16th day to the 40th day. Besides the above symptoms, sluggishness was manifested in group 4 only after a week and lasted for 3 weeks, moreover, 3 chickens died of fluorosis.
Discussion
In the present study, the chicks treated with fluoride showed different degrees of fluorostic symptoms and pathological changes in soft tissues. Consistent with previous reports (Ekambaram and Paul, 2001), serum fluoride concentrations were increased substantially after the oral administration of sodium fluoride. These results suggest that there is a steady rate of absorption of fluoride from the gastrointestinal tract, and the animal models of different degrees of fluorosis were replicated,
Acknowledgements
The authors are grateful to Nature Science Fund Committee of Heilongjiang province in China for financial support and thankful to Professor Shiliang Kang and Yufu Sun for their helpful suggestions. We also thank Mr Willam Derek Artkins from the United States for his advice in grammar and style for the manuscript.
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