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1.
Biofactors ; 45(1): 5-23, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30339717

ABSTRACT

People are exposed to a number of environmental, occupational, and therapeutic toxic agents which may be natural or man made. These hazardous substances may manifest as direct side effects on the function of organs or indirectly induced alteration of gene expression, cancer-associated metabolic pathways, and/or alter homeostasis. Lycopene, as a one of the most potent antioxidant, is found in fruits and vegetables. High-intake of lycopene has been shown to be effective in decreasing the risk of both natural toxins including mycotoxins, bacterial toxins, and chemical toxins including heavy metals, pesticides as well as herbicides. Recently, there is growing attention in understanding the mechanisms of the phytochemicals and carotenoids as antioxidative, antiapoptotic, radical scavenging, and chelating agents and their roles in the modulation of inflammatory pathways. This review summarizes available data from several recent studies about lycopene and its role against chemical and natural toxicants. © 2018 BioFactors, 45(1):5-23, 2019.


Subject(s)
Antioxidants/pharmacology , Bacterial Toxins/antagonists & inhibitors , Chelating Agents/pharmacology , Lycopene/pharmacology , Mycotoxins/antagonists & inhibitors , Pesticides/antagonists & inhibitors , Animals , Antioxidants/metabolism , Bacterial Toxins/toxicity , Chelating Agents/metabolism , Fluorides/antagonists & inhibitors , Fluorides/toxicity , Food Contamination/analysis , Humans , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/toxicity , Lycopene/metabolism , Metabolic Networks and Pathways/drug effects , Metabolic Networks and Pathways/genetics , Metals, Heavy/antagonists & inhibitors , Metals, Heavy/toxicity , Mycotoxins/toxicity , Pesticides/toxicity , Rats , Toxicity Tests, Chronic
2.
Environ Sci Pollut Res Int ; 25(26): 26157-26166, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29971746

ABSTRACT

Fluoride (F-) is becoming an ineluctable environmental pollutant causing deleterious effects in humans. In the present study, we examined whether tamarind seed coat extract (TSCE) is beneficial against the F--induced systemic toxicity and hematological changes. Wistar rats were randomly grouped as follows: group I served as control; group II intoxicated with sodium fluoride (NaF, 300 ppm) in drinking water; group III was administered through oral intubation with TSCE (100 mg/kg bw); group IV was treated with NaF (300 ppm) in association with TSCE (100 mg/kg bw) for 30 days. The results indicated that F- exposure induced oxidative stress as evidenced by elevated levels of reactive oxygen species and lipid peroxidation in the brain, liver, and kidney. F- administration modulates hematological indices-WBC, RBC, and mean corpuscular volume. Moreover, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, acetylcholinesterase, and monoamine oxidase significantly increased on F- exposure. Conversely, δ-aminolevulinic acid dehydratase and glutathione/reduced glutathione ratio were decreased. Activity of antioxidants-superoxide dismutase, catalase, glutathione peroxidase, and vitamin C-was also significantly decreased due to F- administration. Treatment with TSCE effectively mitigated the alterations through its antioxidant potential. The data suggested that the TSCE had beneficial effects in alleviating the F--induced toxicity and hence can serve as a promising neutraceutical agent.


Subject(s)
Antioxidants/pharmacology , Fluorides/antagonists & inhibitors , Plant Extracts/pharmacology , Tamarindus/chemistry , Animals , Antioxidants/metabolism , Ascorbic Acid/metabolism , Aspartate Aminotransferases/metabolism , Catalase/metabolism , Female , Fluorides/pharmacology , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Kidney/drug effects , Lipid Peroxidation/drug effects , Liver/drug effects , Oxidative Stress/drug effects , Porphobilinogen Synthase/metabolism , Rats , Rats, Wistar , Reactive Oxygen Species/metabolism , Seeds/chemistry , Sodium Fluoride/metabolism , Superoxide Dismutase/metabolism
3.
Biol Trace Elem Res ; 181(1): 95-103, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28462439

ABSTRACT

Excessive consumption of fluoride (F) through drinking, eating, and/or environmental contaminants induces chronic toxicity known as fluorosis. Our previous research has shown that fluorosis was associated with male reproductive disorders. The current study is designed to explain the protective effect of vitamin E (VE), insulin-like growth factor-I (IGF-I), and human chorionic gonadotropin (hCG) against natrium fluoride (NaF)-induced alterations in isolated Leydig cells (LCs). These NaF-induced alterations include decreased cell proliferation, steroidogenesis, and relative gene expression. Isolated LCs were incubated with NaF (0, 5, 20 mg/L) and/or 10 µg/ml VE, 100 ng/ml IGF-I, and 100 IU/ml hCG. NaF-treated cells' ability to secrete testosterone (T) was significantly less than other treated groups (P < 0.05). Additionally, in NaF-treated cells, there was a significant upregulation of certain relative mRNA expressions such as Star and Cyp11a, as well as significantly less cell proliferation in a dose-dependent manner (P < 0.05). These data clearly show that VE, IGF-1, and hCG have a protective effect in the LCs functions. Taken together, the final results of this study shown herein are consistent with the assumption that VE, IGF-I, and hCG volunteered ameliorative effects against the deleterious effects of NaF through their protective activity. Although it is hypothesized that ameliorative effects might have been involved, the fundamental pathway(s) remain(s) to be illuminated. Graphical Abstract ᅟ.


Subject(s)
Chorionic Gonadotropin/metabolism , Fluorides/antagonists & inhibitors , Insulin-Like Growth Factor I/metabolism , Leydig Cells/drug effects , Testosterone/metabolism , Vitamin E/metabolism , Animals , Fluorides/pharmacology , Leydig Cells/metabolism , Male , Mice , Mice, Inbred Strains , Testosterone/antagonists & inhibitors
4.
Food Chem Toxicol ; 50(3-4): 583-9, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22198064

ABSTRACT

Fluoride intoxication and dexamethasone treatment produce deleterious effects in bone and brain. The aim of this study was to evaluate the effect of fluoride (F) and dexamethasone (Dex) co-exposure on oxidative stress and apoptosis in osteoblast-like MC3T3-E1 and hippocampal HT22 cell lines. Co-exposure to F and Dex resulted in a concentration-dependent decrease in cell viability, induction of apoptosis and increased generation of reactive oxygen species (ROS) and nitric oxide (NO) following 72 h of incubation. Fluoride-induced apoptosis in MC3T3-E1 and HT22 cells was attenuated by catalase and L-NNMA, indicating a role for H2O2 and NO as mediators of cytotoxicity. Dexamethasone-induced apoptosis was associated with H2O2 generation in both cell lines and it was attenuated during co-incubation with catalase. These data indicate that co-exposure to F and Dex amplifies their respective cytotoxicity in H2O2- and NO-dependent manner. As flavonoid fisetin prevented F- and Dex-induced cytotoxicity the potential role of this product in pharmacology and diet may be considered.


Subject(s)
Dexamethasone/pharmacology , Flavonoids/pharmacology , Fluorides/pharmacology , Hippocampus/drug effects , Osteoblasts/drug effects , Oxidative Stress/drug effects , Animals , Cell Line , Dexamethasone/antagonists & inhibitors , Flavonols , Flow Cytometry , Fluorides/antagonists & inhibitors , Hippocampus/cytology , Osteoblasts/cytology
5.
Food Chem Toxicol ; 48(8-9): 1999-2004, 2010.
Article in English | MEDLINE | ID: mdl-20472017

ABSTRACT

Oxidative damage to cellular components such as lipids and cell membranes by free radicals and other reactive oxygen species is believed to be associated with the development of degenerative diseases. Fluoride intoxication is associated with oxidative stress and altered anti-oxidant defense mechanism. So the present study was extended to investigate black berry anti-oxidant capacity towards superoxide anion radicals, hydroxyl radicals and nitrite in different organs of fluoride-intoxicated rats. The data indicated that sodium fluoride (10.3mg/kg bw) administration induced oxidative stress as evidenced by elevated levels of lipid peroxidation and nitric oxide in red blood cells, kidney, testis and brain tissues. Moreover, significantly decreased glutathione level, total anti-oxidant capacity and superoxide dismutase activity were observed in the examined tissues. On the other hand, the induced oxidative stress and the alterations in anti-oxidant system were normalized by the oral administration of black berry juice (1.6g/kg bw). Therefore it can be concluded that black berry administration could minimize the toxic effects of fluoride indicating its free radical-scavenging and potent anti-oxidant activities.


Subject(s)
Antioxidants/therapeutic use , Fluorides/antagonists & inhibitors , Fluorides/toxicity , Fruit/chemistry , Animals , Antioxidants/chemistry , Fluorides/blood , Glutathione/metabolism , Lipid Peroxidation/drug effects , Nitric Oxide/metabolism , Rats , Superoxide Dismutase/metabolism
6.
Biol Trace Elem Res ; 130(2): 131-40, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19159082

ABSTRACT

Fluoride (F) becomes toxic at higher doses and induces some adverse effects on various organs, including brain. The mechanisms underlying the neurotoxicity caused by excess fluoride still remain unknown. The aims of this study were to examine F-induced oxidative stress (OS) and role of melatonin (MEL) and buffalo pineal proteins (PP) against possible F-induced OS in brain of rats. The 24 rats were taken in present study and were divided into four groups: control, F, F + PP, and F + MEL. The F group was given 150 mg/L orally for 28 days. Combined 150 ppm F and 100 microg/kg BW (i.p.) PP and F (150 ppm) + MEL (10 mg/kg BW, i.p.) were also administered. The activities of enzymatic, viz., superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione reductase (GR), and non-enzymatic, viz., reduced glutathione (GSH) concentration, and the levels of malondialdehyde (MDA) in the brain tissue were measured to assess the OS. Fluoride administration significantly increased brain MDA compared with control group, while GSH levels were decreased in fluoride-treated groups, accompanied by the markedly reduced SOD, GPx, GR, and SOD activity. Buffalo PP and MEL administration caused brain MDA to decrease but caused SOD, GPx, GR, GSH, and CAT activities to increase to significant levels in F-treated animals. Together, our data provide direct evidence that buffalo PP and MEL may protect fluoride-induced OS in brain of rats through mechanisms involving enhancement of enzymatic and non-enzymatic antioxidant defense system. Therefore, this study suggested that PP and MEL can be useful in control of neurotoxicity induced by fluoride.


Subject(s)
Brain/drug effects , Fluorides/toxicity , Melatonin/pharmacology , Oxidative Stress/drug effects , Pineal Gland/metabolism , Proteins/pharmacology , Animals , Buffaloes , Catalase/analysis , Cattle , Female , Fluorides/antagonists & inhibitors , Glutathione/analysis , Glutathione Peroxidase/analysis , Glutathione Reductase/analysis , Lipid Peroxidation/drug effects , Lipid Peroxidation/physiology , Malondialdehyde/analysis , Melatonin/metabolism , Proteins/metabolism , Rats , Rats, Wistar , Superoxide Dismutase/analysis
7.
Bioorg Med Chem Lett ; 14(15): 4103-5, 2004 Aug 02.
Article in English | MEDLINE | ID: mdl-15225735

ABSTRACT

We report on the fluorinated form of Cpd 5 as a cell growth inhibitor. This compound is 3-fold more potent than the parent Cpd 5 and is predicted, using the semi-empirical AM1 method to be only an arylator of cysteine-containing proteins, without generating reactive oxygen species.


Subject(s)
Hydroquinones/antagonists & inhibitors , Benzoquinones/chemical synthesis , Benzoquinones/pharmacology , Fluorides/antagonists & inhibitors , Models, Theoretical , Naphthoquinones/chemical synthesis , Naphthoquinones/pharmacology , Structure-Activity Relationship
8.
Oral Health Prev Dent ; 1(2): 141-8, 2003.
Article in English | MEDLINE | ID: mdl-15645935

ABSTRACT

PURPOSE: High-fluoride drinking water represents a health hazard to millions of people, not least in the East African Rift Valley. The aim of the present project was to establish a simple method for removing excessive fluoride from water. MATERIAL AND METHODS: Based on geological maps and previous experience, 22 soil samples were selected in mountainous areas in central Ethiopia. Two experiments were performed: 1. After sieving and drying, two portions of 50 g were prepared from each soil and subsequently mixed with solutions of NaF (500 mL). Aliquots (5 mL) of the solutions were taken at pre-set intervals of 1 hour to 30 days for fluoride analysis--using an F-selective electrode. 2. After the termination of the 30-days test, liquids were decanted and the two soil samples that had most effectively removed fluoride from the NaF solutions were dried, and subsequently exposed to 500 mL aqua destillata. The possible F-release into the distilled water was assessed regularly. RESULTS: Great variations in fluoride binding patterns were observed in the different soils. The percent change in F-concentration in the solutions, as compared to the original absolute value(F-), varied: at 1 hour from a decrease of 58% to an actual increase of 7.7%, while--at 30 days--all soil samples had caused a decrease in the F-concentration, varying from 0.5% to 98.5%. Only minute amounts of fluoride would leach from the fluoride-enriched soils. CONCLUSION: Lateritic soils may remove excessive fluoride from drinking water. Methods for practical application of this principle should be tested at household level.


Subject(s)
Fluorides/antagonists & inhibitors , Soil , Water Pollution, Chemical , Water Supply , Desiccation , Diffusion , Ethiopia , Fluorides/analysis , Fluorides/chemistry , Humans , Ion-Selective Electrodes , Public Health , Sodium Fluoride/analysis , Sodium Fluoride/antagonists & inhibitors , Sodium Fluoride/chemistry , Soil/analysis , Time Factors , Water Pollution, Chemical/analysis , Water Supply/analysis
9.
Mol Cell Biochem ; 234-235(1-2): 335-40, 2002.
Article in English | MEDLINE | ID: mdl-12162452

ABSTRACT

The objective of the present communication is to address the issues concerning reversal of fluoride induced cell injury and disease (i.e. fluorosis) through the elimination of fluoride and consumption of a diet containing essential nutrients and antioxidants. Humans afflicted with fluorosis, as a result of consuming fluoride contaminated water or food, have been investigated. Hospital based diagnostic procedure for early detection of fluorosis, through retrieval of history, clinical complaints, testing of blood, urine and drinking water for fluoride using ion selective electrode technology, along with X-ray of the forearm have been carried out. Confirmed cases of fluorosis were introduced to an intervention protocol consisting of (1) provision of safe drinking water with fluoride levels less than 1 mg/L and (2) counselling on nutritional supplementation with focus on adequate intake of calcium, vitamins C, E and antioxidants. The patients were monitored at frequent intervals up to one year and the results are reported. With a standardized early diagnosis, elimination of fluoride intake and supplementation of a diet rich in essential nutrients and antioxidants, we have shown that the fluorosis can be reversed.


Subject(s)
Antioxidants/pharmacology , Antioxidants/therapeutic use , Fluoride Poisoning/drug therapy , Fluorides/adverse effects , Fluorides/antagonists & inhibitors , Adolescent , Adult , Cell Death/drug effects , Child , Feeding Behavior , Female , Fluoride Poisoning/diagnosis , Fluoride Poisoning/physiopathology , Fluorides/blood , Fluorides/urine , Humans , Male , Middle Aged
10.
Wei Sheng Yan Jiu ; 31(2): 81-2, 99, 2002 Apr.
Article in Chinese | MEDLINE | ID: mdl-12561534

ABSTRACT

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.


Subject(s)
Boron/pharmacokinetics , Fluoride Poisoning/metabolism , Fluorides/antagonists & inhibitors , Zinc/pharmacokinetics , Animals , Bone and Bones/metabolism , Female , Liver/metabolism , Male , Random Allocation , Rats
11.
Wei Sheng Yan Jiu ; 31(2): 136-8, 2002 Apr.
Article in Chinese | MEDLINE | ID: mdl-12561555

ABSTRACT

Hydroxyapatite as a defluoridator for drinking water is characterized by a large capacity of defluoridation, and easy and simple operation in application. The quality of drinking water is not changed, the sorbent is easy to be regenerated, and the second pollution does not occur after the treatment of drinking water with the sorbent. Hydroxyapatite method has advantage over the methods such as actived alumina, bone char and electrodialysis commonly used in defluorination of drinking water. It is for this reason that the components, structural feature, synthesis and application of hydroxyapatite and its mechanism of defluoridation are summarized in this paper.


Subject(s)
Durapatite/chemical synthesis , Fluoridation , Fluorides/antagonists & inhibitors , Fluorides/adverse effects
12.
J Toxicol Clin Toxicol ; 39(4): 349-53, 2001.
Article in English | MEDLINE | ID: mdl-11527228

ABSTRACT

OBJECTIVES: Acute systemic fluoride poisoning can result in systemic hypocalcemia, cardiac dysrhythmias, and cardiovascular collapse. Topical and intraarterial therapy with calcium or magnesium salts reduces dermal injury from fluoride burns. The mechanism of these therapies is to bind and inactivate the fluoride ion. The purpose of this study is to evaluate the effect of calcium and magnesium to decrease the bioavailability of fluoride in a lethal model of fluoride poisoning. METHODS: In preliminary studies, we determined that fluoride 3.6 mM/kg intraperitoneally in the form of sodium fluoride was uniformly and rapidly fatal in a mouse model. Using this fluoride dose, we performed a controlled, randomized, blinded study of low- and high-dose calcium chloride (1.8 and 3.6 mM/kg intraperitoneally, respectively) and magnesium sulfate (3.6 mM/kg intraperitoneally) to decrease the bioavailability of the fluoride ion. After injection with sodium fluoride, animals were immediately treated with injections of sodium chloride (control), calcium chloride (low- or high-dose), or magnesium sulfate. The major outcome was 6-hour survival using a Cox Proportional Hazard model. RESULTS: All untreated animals died within 60 minutes. Using a Cox Proportional Hazard model, each 1.8 mM/kg dose of calcium chloride administered reduced the risk of death by 33%. Magnesium sulfate treatment was not associated with a hazard reduction. CONCLUSION: Calcium chloride administered simultaneously with sodium fluoride reduces the bioavailability of fluoride poisoning in a mouse model. The equivalent dose of magnesium sulfate does not significantly decrease fluoride bioavailability.


Subject(s)
Calcium/pharmacology , Fluorides/antagonists & inhibitors , Fluorides/toxicity , Animals , Biological Availability , Fluorides/pharmacokinetics , Magnesium/pharmacology , Male , Mice , Survival Analysis
13.
Neurotoxicol Teratol ; 23(2): 197-201, 2001.
Article in English | MEDLINE | ID: mdl-11348838

ABSTRACT

We have evaluated the ameliorative effect of vitamin D on fluoride-induced embryotoxicity in pregnant rats. Oral administration of sodium fluoride (NaF; 40 mg/kg body weight) from days 6 to 19 of gestation caused, as compared with control, significantly lowered body weight, feed consumption, absolute uterine weight and number of implantations. As compared with the control, higher incidence of skeletal (presence of wavy ribs, 14th rib, dumbbell-shaped 5th sternebrae, incomplete ossification of skull) and visceral (subcutaneous haemorrhage) abnormalities was recorded in the foetuses of fluoride-treated pregnant rat. Vitamin D (2 ng/0.2 ml olive oil/animal/day po) treatment significantly ameliorated the fluoride-induced reductions in body weight, feed consumption and absolute uterine weight. As compared with fluoride-treated alone, the total percentage of skeletal and visceral abnormalities observed in foetuses was significantly lowered in fluoride plus vitamin D-treated animals. These findings suggest that vitamin D treatment significantly reduced the severity and incidence of fluoride-induced embryotoxicity. The ameliorative effect of vitamin D against skeletal and visceral abnormalities could be due to stimulation of intestinal absorption of calcium and phosphate, thus raising the plasma calcium and phosphate concentrations.


Subject(s)
Embryo, Mammalian/drug effects , Fluorides/antagonists & inhibitors , Fluorides/toxicity , Teratogens/toxicity , Vitamin D/pharmacology , Abnormalities, Drug-Induced/pathology , Animals , Body Weight/drug effects , Eating/drug effects , Female , Pregnancy , Rats , Rats, Wistar
14.
Oral Dis ; 5(2): 100-3, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10522204

ABSTRACT

OBJECTIVE: Results from previous studies have shown that pre- and perinatal exposure to lead enhances susceptibility of rats to development of dental caries. A possible explanation for this phenomenon may be that lead complexes with fluoride and renders F insoluble and unable to exert its cariostatic effects. MATERIALS AND METHODS: Thus, to explore this hypothesis, 48 desalivated Sprague-Dawley rats were placed in a König-Höfer programmed feeder and received 17 meals of powdered sucrose daily, and water ad libitum as follows: group (1) plain sucrose and sterile distilled water (SDW); (2) sucrose containing 15 ppm F and SDW; (3) sucrose containing 15 ppm F and 10 ppm Pb water; (4) sucrose containing 15 ppm F and 25 ppm Pb water. RESULTS: The highest smooth-surface, sulcal surface caries and severity scores were observed in group I. Animals that were exposed to fluoride showed reduced smooth-surface caries and severity scores. S. sobrinus counts did not differ among the groups. CONCLUSION: Lead did not interfere with the protective effect of fluoride in the conditions of the present study.


Subject(s)
Cariostatic Agents/chemistry , Fluorides/chemistry , Lead/chemistry , Animals , Biological Availability , Dental Caries/etiology , Female , Fluorides/antagonists & inhibitors , Fluorides/pharmacokinetics , Lead/pharmacology , Rats , Rats, Sprague-Dawley , Saliva/physiology , Sucrose/adverse effects , Sucrose/chemistry
15.
Eur J Pharmacol ; 350(2-3): 189-94, 1998 Jun 05.
Article in English | MEDLINE | ID: mdl-9696407

ABSTRACT

In papillary muscles, carbachol reduced the positive inotropic effects of isoprenaline (10 nmol/l). The negative inotropic effects of carbachol in isoprenaline-stimulated guinea pig papillary muscles were attenuated by additionally applied sodium fluoride (3 mmol/l). These effects of sodium fluoride were blocked by deferoxamine (200 micromol/l). In guinea pig left atria, sodium fluoride alone greatly reduced force of contraction. These effects in atria were blocked by 200 micromol/l deferoxamine, and positive inotropic effects of sodium fluoride were observed. It is suggested that the cardiac effects of muscarinic M2 receptor agonists in the ventricle involve, at least in part, the activation of phosphatases which are blocked by fluoride and reactivated by deferoxamine.


Subject(s)
Carbachol/antagonists & inhibitors , Deferoxamine/pharmacology , Fluorides/antagonists & inhibitors , Heart/drug effects , Iron Chelating Agents/pharmacology , Muscarinic Agonists/pharmacology , Adrenergic beta-Agonists/pharmacology , Animals , Carbachol/pharmacology , Fluorides/pharmacology , Guinea Pigs , In Vitro Techniques , Isoproterenol/pharmacology , Myocardial Contraction/drug effects , Myocardium/enzymology , Papillary Muscles/drug effects , Papillary Muscles/enzymology , Phosphoprotein Phosphatases/metabolism , Rats
17.
Wei Sheng Yan Jiu ; 27(3): 201-4, 1998 May.
Article in Chinese | MEDLINE | ID: mdl-10684132

ABSTRACT

Five groups of SD male rats were provided with deionized drinking water containing 0 and 150 mg/L NaF, and containing both 150 mg/L NaF and 0.5, 2.0 or 4.0 mg/L Na2SeO3 respectively for 10 weeks, in order to find out the optimal level of selenite in drinking water against fluoride toxicity. The results showed that fluoride could cause significant increase of lipid peroxides (LPO) and metabolic disorder of trace elements in the serum and kidney of rats. The antagonistic effect of 2.0 mg/L Na2SeO3 drinking water on the lipid peroxidation induced by 150 mg/LNaF was the most evident, whereas those of 0.5 and 4.0 mg/L Na2SeO3 were not obvious. It is concluded that selenite possesses significant antagonistic effects on renal damages induced by fluoride and 2.0 mg/L Na2SeO3 is the optimal concentration for the antagonistic effect on renal impairments induced by 150 mg/L NaF in drinking water.


Subject(s)
Fluorides/antagonists & inhibitors , Kidney/metabolism , Lipid Peroxidation/drug effects , Sodium Selenite/pharmacology , Zinc/metabolism , Animals , Copper/metabolism , Male , Rats , Rats, Sprague-Dawley
18.
Wei Sheng Yan Jiu ; 26(4): 233-8, 1997 Jul.
Article in Chinese | MEDLINE | ID: mdl-10325593

ABSTRACT

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.


Subject(s)
Fluoride Poisoning/metabolism , Fluorides/pharmacokinetics , Selenium/pharmacology , Animals , Fluorides/antagonists & inhibitors , Male , Random Allocation , Rats , Rats, Wistar
19.
Arch Toxicol ; 72(1): 52-8, 1997.
Article in English | MEDLINE | ID: mdl-9458191

ABSTRACT

Although an excess intake of fluoride has been reported to cause skeletal fluorosis, very little is known about the mechanism of adverse effects of fluoride on bone. In the present study cytotoxic effects of fluoride were studied using the osteosarcoma cell line, UMR 106. The DNA ladder formation upon agarose electrophoresis and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) staining revealed that UMR 106 underwent apoptosis following exposure to 5 mM fluoride for 8 h. On the other hand exposure to A23187, a calcium ionophore, caused necrosis while co-exposure to fluoride and A23187 inhibited fluoride-mediated apoptosis in UMR 106. The proliferation of UMR 106 cells cultured for 6 days in the presence of 0.5 mM fluoride was significantly decreased compared to the control culture. The cytotoxic effects of fluoride were modulated by both the cell density and the pH of the culture medium. The fluoride-induced viability loss in UMR 106 was enhanced in culture of high cell-density and inversely correlated with pH of the culture medium. Enhancement of fluoride cytotoxicity at acidic pH was also observed in rat alveolar macrophages and RAW 264, a macrophage cell line. The results suggest that fluoride-mediated apoptosis and culture conditions, including pH of the medium, should be taken into consideration to evaluate toxicity of fluoride in vitro.


Subject(s)
Apoptosis/drug effects , Fluorides/toxicity , Animals , Apoptosis/genetics , Bone Neoplasms , Calcimycin/toxicity , Cell Count/drug effects , Cell Line/drug effects , Cell Survival/drug effects , Culture Media , DNA Fragmentation , Dose-Response Relationship, Drug , Fluorides/antagonists & inhibitors , Hydrogen-Ion Concentration , Ionophores/toxicity , Macrophages, Alveolar/drug effects , Mice , Necrosis , Osteosarcoma , Rats , Tumor Cells, Cultured/drug effects
20.
Biochem Biophys Res Commun ; 205(1): 245-50, 1994 Nov 30.
Article in English | MEDLINE | ID: mdl-7999031

ABSTRACT

These studies sought to determine the effects of neomycin, a phospholipase C inhibitor, on hormone-stimulated myometrial contractions. For these studies, computer digitalized in vitro isometric contraction data were analyzed for changes in contractile activity in response to oxytocin and aluminum fluoride with and without neomycin. Neomycin (1-5 mM) produced dose-related inhibition of oxytocin and aluminum fluoride-stimulated myometrial contractions. This neomycin effect was apparent within 2-3 minutes of addition and was completely reversible, with resolution of its inhibitory effects within 6-8 minutes of washout. This study is the first to demonstrate the functional effect of neomycin inhibition of the phosphatidylinositol signaling pathway in myometrial smooth muscle tissue.


Subject(s)
Myometrium/drug effects , Neomycin/pharmacology , Oxytocin/antagonists & inhibitors , Aluminum Compounds/antagonists & inhibitors , Aluminum Compounds/pharmacology , Animals , Female , Fluorides/antagonists & inhibitors , Fluorides/pharmacology , In Vitro Techniques , Isometric Contraction/drug effects , Myometrium/physiology , Oxytocin/pharmacology , Rats , Rats, Sprague-Dawley , Signal Transduction
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