Life in plants and animals, including humans, depends on the orderly occurrence of a myriad of biochemical reactions which allow the harnessing of energy from the sun or food, the functioning of various organ systems, and the synthesis of an array of products including lipids, carbohydrates, and proteins. These reactions are sensitive to disruption by poisons such as cyanide ions which can, depending on the dose and route of administration, kill or cause chronic toxicity by inactivating cytochrome oxidase at cytochrome a3, thus uncoupling mitochondrial oxidative phosphorylation and inhibiting cellular respiration, even in the presence of adequate oxygen stores. The fluoride ion shares with the cyanide ion the capacity to impair the function of the mitochondrial enzyme cytochrome oxidase and cause both acute and chronic toxicity. In addition, fluoride can, along with other actions, decrease the activities of mitochondrial succinate dehydrogenase and Mg²⁺-adenosine triphosphatase. These biochemical and physiological injuries underlie the visible symptoms of damage to plants or clinical illness in animals from fluoride toxicity. Their presence may be assessed by the measurement of various parameters such as enzyme levels, gene expression levels, and metabolite levels, and also by examining structural changes at the ultrastructural level.

Chronic fluoride toxicity may cause a number of nonspecific symptoms affecting a number of organ systems such as chronic fatigue not relieved by extra sleep or rest, headaches, dryness of the throat and excessive water consumption, urinary frequency, urinary tract irritation, muscle and joint aches and stiffness, muscle weakness and spasms, paraesthesiae, gastrointestinal disturbances, skin maculae and rashes, cognitive impairment, mood disturbance, balance difficulties, visual disturbances, brittle nails, repeated miscarriages or still births, male infertility, and tooth discolouration. Critics of the existence of the syndrome of chronic fluoride toxicity have considered that the so-called “fluoride intolerance” is in fact a variety of unrelated conditions or has a psychogenic or psychosomatic basis. However, if an underlying cellular dysfunction, such as mitochondrial impairment, common to all the organ systems, was involved a disturbance in many organ systems would be expected.

The demonstration of disturbances at the cellular level, as detected by the measurement of various parameters and by observing ultrastructural changes, is a way of countering the argument that chronic fluoride toxicity is not an important issue for populations exposed to compulsory water fluoridation as occurs, in part or in all, of a number of countries including the USA, Canada, Iceland, Ireland, Israel, Australia, Singapore, and New Zealand. Ultrastructure studies have also been recommended in order to better understand the mechanisms of fluoride toxicity. In 1993, Chinoy, Sharma, and Michael stated that detailed studies, in fluoride toxicity, of the ultrastructure of muscle, especially its mitochondria were called for. Again in 1999, Chinoy and Patel noted that severe structural alternations had been found, with fluoride toxicity, in the mitochondria of guinea pig liver and in mice liver and kidney, and they called for further ultrastructural studies in the future.

In reviewing the area, I found that ultrastructural studies have been made of the horse-bean plant, Vicia Faba L., and various animal species including humans, mice, rats, rabbits, guinea pigs, pigs, and chickens. The animal tissues studied included the liver, pancreas, testis, submandibular gland, kidney, thyroid, myocardium, skeletal muscle, sciatic nerve, spinal cord, cerebellum, hippocampus, neocortex, femur, spleen, ovary, and uterus.

In the plant study fluoride led to a high activity of the Golgi apparatus and an obvious destruction of the photosynthetic apparatus with the chloroplasts of the mesophyll cells a showing lack of grana and dilation of the thylacoids.

In the animal studies there were variable effects on the Golgi apparatus but typically the mitochondria were enlarged with disrupted cristae and the rough endoplasmic reticulum was reduced in extent, irregular, dilated, and disrupted. For example, in a study of the cerebral cortex of human foetuses affected by fluoride toxicity, the nerve cells contained fewer mitochondria, granular endoplasmic reticula, and ribosomes than the controls. The mitochondria showed marked swelling, the granular endoplasmic reticula had expanded, and the nuclear membranes were damaged, with the contents of the nucleus spilling out of the nuclear envelope. Within the nucleus, there was an increase in heterochromatin, with some grouping around the edges. Synapses were relatively rare, and those noted were enlarged, with the synaptic membrane broken and fewer mitochondria, microtubules, and vesicles than usual.

Some studies considered the time required for ultrastructural changes to occur. In the plant study destruction of the photosynthetic apparatus was apparent 24 hr after fumigation with hydrogen fluoride was initiated. In a human study of skeletal muscle two hours incubation with sodium fluoride was sufficient time to produce disintegration of the mitochondrial cristae and a decrease in the density of the mitochondrial matrix.

In conclusion, ultrastructural studies of fluoride toxicity help elucidate the mechanisms by which the signs and symptoms of the condition emerge and the basis for many organ systems being involved.

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