Rescuing fluoride-induced damages in liver with gamma aminobutyric acid.

Fluorine poisoning affects human health all over the world and an urgent task is to develop alleviative medicine to recover or ameliorate the damages to the body. Here we studied the effects of gamma-aminobutyric acid (GABA), a liver protector reported previously, on fluoride-induced damage in the mouse liver. Through microscope imaging of the liver tissue, TUNEL immunostaining, real-time RT-PCR, enzyme immunoassay and colorimetric method, we found that GABA supplementation prevented the metabolic toxicity caused by fluoride treatment in mice. This detoxification was reflected by the reduced oxidative stress and apoptosis, enhanced neuron protection and liver function. Collectively, this study provided evidence of the beneficial effects of GABA supplement on liver damage, implicating its therapeutic potential in fluorosis.

[Effect of fluoride on expression of CaN mRNA and protein in bone tissue of rats].

OBJECTIVE: To investigate the changes of mRNA and protein expression of CaN in the bone of rats with chronic fluorosis, and the mechanism of skeletal fluorosis. METHODS: Thirty-six SD rats were divided into three groups (12 in each group, half male and half female selected according to body weight): control, low-dose and high-dose fluorosis groups. Controls were fed tap water (NaF < 0.5 mg/L), experimental animals in the low- or high-dose groups were fed water containing NaF of 5.0 and 50.0 mg/L, respectively. The rats were sacrificed after 6 months of treatment with fluoride. The serum was kept for testing bone metabolic marker bone gla protein (BGP) by enzyme-linked immunosorbent assay (ELISA), the protein and mRNA levels of CaN in distal femur of the rats with chronic flurosis were assessed by immunohistochemistry and in-situ hybridization. RESULTS: The levels of BGP (1.99 ± 0.62, 2.38 ± 0.16)µg/L in the low- or high-dose fluorosis groups were higher than that in the control group (0.15 ± 0.03) µg/L; and the high fluorosis group showed higher level than the low fluorosis group (all P < 0.05). Compared to the control group (131.11 ± 1.95, 111.82 ± 2.39), the protein and mRNA levels of CaN were higher in the low- or high-dose fluorosis groups (142.69 ± 1.17, 157.54 ± 1.88 and 121.28 ± 3.27, 134.63 ± 3.19, respectively), and the high fluorosis group showed higher levels than the low fluorosis group (all P < 0.05). CONCLUSIONS: BGP content could be used as a bone metabolic index in endemic fluorosis disease. Fluoride might up-regulate the mRNA and protein expression of CaN, and the changes in CaN level may be involved in the increase of the bone turnover and could be one of the pathogenetic factors in fluorosis.

Antioxidant and ACE enhancing potential of Pankajakasthuri in fluoride toxicity: an in vitro study on mammalian lungs.

Fluoride toxicity occurs due to high concentrations of fluoride in water sources or anthropogenic causes. The aim of the present study was to investigate the effects of an Ayurvedic drug--Pankajakasthuri (PK)--in relation to fluoride-induced toxicity in mammalian lungs. The results indicated that sodium fluoride increased lipid peroxidation and decreased enzymatic and non-enzymatic antioxidants in a concentration-dependent manner in lungs. The antioxidant potential of the lungs was suppressed maximally at 10 ppm fluoride concentration and PK at all three dose levels (i.e., 100, 200 and 300 µl) decreased fluoride induced lipid peroxidation (p < 0.05) and increased the levels of total ascorbic acid, superoxide dismutase, catalase, reduced glutathione, glutathione peroxidase and FRAP values significantly (p < 0.05) in a dose-dependent manner. When PK was examined for its effects on angiotensin-converting enzyme (ACE) activity, in fluoride-induced toxicity, the ACE activity was found to increase (p < 0.0001) in lung homogenates with all three doses. This study indicates that PK, an Ayurvedic drug, improves mammalian lung function by increasing antioxidant potential and ACE activity under the conditions of fluoride toxicity.

Selenium increases expression of HSP70 and antioxidant enzymes to lessen oxidative damage in Fincoal-type fluorosis.

Fincoal type fluorosis has only been reported from China, but its pathogenesis is unclear. Many people believe that fluorosis is associated with oxidative stress. Oxidative stress can be reduced at higher selenium (Se) level. Heat shock protein (HSP70) is the most conserved and induced against different stressors. The aim of this study is to detect the expression of HSP70 in fluorosis patients and explore the role of Se in fluorosis protection. The subjects were divided into four groups: "High Se + F group" (n = 50), "High F group" (n = 50), "High Se group" (n = 20) and "Control group" (n = 46). Expression of HSP70 was evaluated by Western blotting and real-time PCR techniques. The concentration of fluoride, content of Se in hair, activity of antioxidant enzymes (GSH-Px, SOD, CAT) and content of malondialdehyde (MDA) were determined. The relative amount of HSP70 gene transcription was significantly higher in "High Se + F group" than the other groups. The same results were found for expression of HSP70 protein to beta-actin ratio. There was a significant difference between "High Se + F group" and "High F group" regarding MDA content and glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) activity. These results suggest that oxidative stress plays an important role in the pathogenesis of the Fincoal type fluorosis and it can be reduced at higher Se level.

[Studies on fluoride concentration and cholinesterase activity in rat hippocampus].

OBJECTIVE: To study the accumulation of fluoride in rat hippocampus and its effect on cholinesterase activity. METHODS: Rats were subchronically exposed to NaF, and fluoride concentration and cholinesterase activity in rat hippocampus were determined. RESULTS: Fluoride concentration in rat hippocampus was significantly correlated with the dosage of fluoride, and there were significant differences among high dosage group [(13.03 +/- 1.79) micro g/g], low dosage group [(9.83 +/- 0.92) micro g/g] and control [(8.27 +/- 1.11) micro g/g], P < 0.01. Acetylcholinesterase activities among three groups [(0.111 +/- 0.031) micro mol/mg, (0.143 +/- 0.025) micro mol/mg, (0.183 +/- 0.027) micro mol/mg] were also significantly different (P < 0.01), which was negatively correlated with fluoride concentration in rat hippocampus (r = -0.700, P < 0.01). The activity of butylcholinesterase in high dosage group [(0.041 +/- 0.010) micro mol/mg] was different from that of control [(0.067 +/- 0.025) micro mol/mg, P < 0.05], but the activity was not significantly related with fluoride concentration in rat hippocampus (r = -0.317, P = 0.094). CONCLUSION: Fluoride may go through the blood-brain barrier and accumulate in rat hippocampus, and inhibit the activity of cholinesterase.

[Study on metabolism of preventive anti-fluorine agent on rats].

In order to study the metabolism of preventive anti-fluorine agent, 30 rats are randomly divided into high-dose, low-dose and a control groups. The high dose (400 mg/kg.d) and low dose (16 mg/kg.d) are orally administrated respectively, and the content of boron and/or zinc in urine, dung, serum, bone, liver, muscles, brain tissues is determined. The results showed that during the administration of this agent, the content of boron in urine and the content of zinc in dung increases obviously in both high-dose and low-dose groups and their discharge rate is consistent with the dose given. The content of boron and zinc in bone, liver, and zinc in serum, muscles, brain tissues increases evidently compared to that in control group but decreases rapidly after administration of the agent. The findings revealed that there is a rapid metabolism of boron and zinc in the body of rats. The highest content of the agent is observed in bones. The content ranks second in liver and muscles but no accumulative effects are observed.

[Metabolic effect of amaranth oil and impulse hypoxic training under chronic fluoride intoxication and small doses of ionizing radiation]. / Metabolichni efekty oliï amarantu ta impul'snoho hipoksychnoho trenuvannia za umov diï ftorystoï intoksykatsiï ta malykh doz radiatsiï.

Lipid peroxidation and antioxidative defence system in blood, liver and heart tissues, nitric oxide metabolites content in brain tissue of rats under binary action of small-doses of ionizing radiation and fluoride intoxication treated by amaranth oil and interval hypoxic training have been studied. Complex using of amaranth oil and interval hypoxic training result in increase both enzymatic, as nonezymatic links of antioxidant defence in all investigated tissues. It was revealed also enhance of NO system metabolites content in brain gomogenate. In this conditions lipid peroxidation processes in liver and heart tissues normalize comparison with essential increase level LPO under binary action influence. On the basis of obtained results LPO metabolites content we can suppossed that complex using of amaranth oil and interval hypoxic training result in increase of organism adaptative possibility. This complex can be using for binary action of ionizing radiation and fluoride intoxication correction.

[Study on antagonistic effects of selenium and zinc on the renal impairments induced by fluoride in rats].

Wistar rats were provided with distilled water containing NaF(100 mg/L), and were administered through gavage with Na2SeO3[0.1 mg/(kgBW.d)] and/or ZnSO4[14.8 mg/(kg BW.d)]. The results of biochemical, pathological and ultrastructural examinations showed that fluoride could cause serious renal impairments. The major damage induced by fluoride was epithelia of proximal renal tubules. The lipid peroxidation might be one of the mechanisms of fluoride toxicity. Na2SeO3 and ZnSO4 could antagonize the renal impairments induced by fluoride through their antioxidation. The cooperative effect of Na2SeO3 and ZnSO4 was more powerful than either Na2SeO3 or ZnSO4 alone.

[Accumulation and excretion of fluorine and effect of selenium on them in rats with chronic fluorosis].

2 groups of Wistar rats with chronic fluorosis were duplicated with 30 and 50 mg/L fluorine (F) in drinking water. 2. 0 mg/kg selenium (Se) in fodder was supplemented in the other 2 groups of rats with fluorosis. The amount of drinking water and diet, the excretion of urine and the contents of urine F were tendentiously surveyed every month in one year and then, intake and excretion of F were calculated per day. The contents of Se in urine, liver and serum and F in bone, liver, kidney and serum were measured in the 4th, 8th, and 14th month. The results showed that F absorption increased and F excretion/F absorption rate decreased in 2 groups of rats with fluorosis compared with control group and there were positive correlations between concentration of urine F and water F, as well as concentration of F urine and time of drinking F water. The accumulation of F in bone and liver occurred in the middle period of fluorosis and then, the increase of serum F was observed in the late period of fluorosis in 2 groups of rats with fluorosis. After supplement of Se, urine, liver and serum Se ascended. At the same time, state of eating and drinking improved, the weight rose and the amount of urine excretion heightened, as well as there was an increase of urine F and excretion F/absorption F rate and there was a decrease of bone, live, kidney and serum F in rat of Se supplementation with fluorosis compared with non-Se groups.

[Changes in energy metabolism parameters of the liver in acute fluoride intoxication and hyperbaric oxygenation]. / Zmina pokaznykiv energetychnogo metabolizmu v pechintsi pry gostrii intoksykatsii ftorydom natriiu i zastosuvanni giperbarychnoi oksygenatsii.

Examinations of energetic metabolism in liver of white rats with acute fluoride intoxication were carried out in acute and recovering periods. The influence of hyperbaric oxygenation on the change of energetic metabolism indices and on survival rates of animals has been studied. Hyperbaric oxygenation greatly prevented profound metabolic disturbances, in particular, ATP, increased detoxic in liver intensifying energetic forming processes. The survival rate of animals under the influence of course of HBO increased by 27% during first 72 hours. It was determined that HBO has an effective influence on the course of recovering period during fluoride intoxication.

[Changes of energy metabolism and concentration of cyclic nucleotides in the kidneys in acute fluoride intoxication and hyperbaric oxygenation]. / Zminy energetychnogo metabolizmy i kontsentratsii tsyklichnykh nukleotydiv u nyrkakh pry gostrii ftorystii intoksykatsii i zastosyvanni giperbarychnoi oksygenatsii.

The energy metabolism and indices of the adenylate-cyclase system in kidneys of rats with acute fluoric intoxication have been studied. It has been determined that the use of hyperbaric oxygenation prevents deep disturbances of energy metabolism in the renal tissue and restricts the increase of adenosine monophosphate concentration. Moreover the survival rate of animals has increased by 30% for the first 24 hours.

[Oxygen balance and the effect of antihypoxic preparations in fluorine poisoning]. / Kislorodnyi balans i vliianie protivogipoksicheskikh preparatov pri intoksikatsii ftorom.

Long-term inhalations of fluoride at concentrations of 0.58 and 2.75 mg/m3 distrub oxygen regimen in experimental animals (O2 consumption, tension and utilization in the muscle, tissue respiration). During fluorine intoxication, some of the antihypoxic agents (NAD X H, adenine nucleotides, guthimin, bemitil, apressin and glutamic acid) exert a beneficial therapeutic effect. Administration of the glycolysis substrates, NAD, NADP, cytochrome c and sodium hydroxybutyrate, did not exert any marked therapeutic action.

[Effect of different kinds of Ocean paste on rat liver biochemical indices in sodium fluoride poisoning]. / Vliianie razlichnzkh vidov pasty "Okean" na biokhimicheskie pokazateli pecheni krys pri intoksikatsii, vyzvannoi ftoridom natriia.

The paper is concerned with the effect of diets including three chemically different types of the "Ocean" paste on biochemical characteristics (glycolysis, the content of phosphofructokinase, dehydrogenase, glucoso-6- phosphate, demethylase, dimethylalaniline hydroxylase, ascorbic acid) of the liver of rats exposed to sodium fluoride overdosage. The test diets were compared with those containing conventional sources of protein (casein, beef). Acute exposure to sodium fluoride caused changes in the biochemical characteristics. The most appreciable changes were seen in the group of rats fed beef. As compared with control, the shifts in the biochemical characteristics were negligible provided the rats exposed to acute and chronic poisoning received the diet supplemented with the paste. No morphological changes were found in the internal organs. The data obtained indicate that the type C "Ocean" paste has a protective action in sodium fluoride poisoning.

Alleviation of fluorine toxicity in starting turkeys and chicks with aluminum.

Aluminum (Al) compounds were evaluated as fluorine (F) toxicity alleviators in starting broiler chicks and turkeys. Added F levels from NaF ranged from 0 to 1000 ppm, whereas Al levels varied from 0 to 800 ppm. Al was fed either as Al2O3 or Al2 (SO4)3.18H2O. When fed as the sulphate salt, 800 ppm of Al completely prevented the toxic effect of at least 1000 ppm of F. Al2O3 was not effective as an alleviator of fluorine toxicity. When the mode of action of Al2(SO4)3.18H2O against F toxicity was studied in colostomized turkeys it was apparent that F absorption occurred but was probably less efficient than previously reported in ruminants. Al significantly (P less than .05) reduced F absorption in turkeys. Urinary F levels were: 2.4 ppm in birds fed a control diet (26 ppm F), 17.8 ppm in birds fed a diet with 1000 ppm F, and 6.7 ppm in birds fed the high F diet with 800 ppm Al as the sulphate salt. In addition, data from this study indicated that starting broiler chicks were more tolerant (800 ppm F) than starting turkeys (600 ppm F) to fluorine toxicosis.

An electron microprobe analysis of osteofluorosis in the rabbit.

Osteofluorosis was induced in rabbits by the ingestion of 500 ppm F in their drinking water over a period of 30 days. The tibiae from experimental and control animals were selected for macroscopic, microscopic and microradiographic observation. Transverse sections of 100 mum thickness were prepared for an electron-microprobe analysis to determine Ca, P and F concentrations and to display the topographical distribution of F as revealed by the X-ray image of its Kalpha1 radiation. Variation in amount of periosteal and endosteal deposition was observed along the length of the bone. Changes, including numerous mottled osteones, were seen in the compact zone of bone which had been formed prior to the start of the experiment. The Ca/P ratio appeared to show a variation related to the F concentration.