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A multigrain protein enriched diet mitigates fluoride toxicity
Abstract
Fluorosis is a major health problem in many parts of the world. The present work focuses on investigating the utility of nutrient and antioxidant rich grains- ragi, jowar, bajra, maize in formulation of basal, high carbohydrate low protein and low carbohydrate high protein diets in mitigating fluoride toxicity. Exposure to fluoride through drinking water not only significantly increased plasma glucose and lipid profiles, but also elevated both hepatic and renal lipid peroxidation, hepatic lipid profiles and G-6-Pase activity with a reduction in plasma HDL-C, hepatic glycogen content, hexokinase activity and antioxidant status. Even though basal and high carbohydrate diets did not significantly alter plasma glucose, lipid profiles in fluoride administered animals, protein enriched multigrain diet significantly decreased plasma glucose and lipid levels. However, the multigrain basal and high carbohydrate diets influenced the hepatic glycogen, lipid profiles, hexokinase and G-6-Pase activities, hepatic and renal lipid peroxidation and antioxidant status though not as significantly as that of multigrain diet enriched with protein. Thus the results of the present study indicate that both a multigrain diet rich in nutrients and antioxidants, and fortified with protein is useful in mitigating the fluoride toxicity.
... En el caso de las características de los individuos, la exposición a las alturas grandes conlleva un respiración más rápida y profunda dada la menor oxigenación, acelerando la formación y evaporación de sudor y llevando a mayores micciones urinarias; a su vez este tipo de respiración adaptada a las alturas promueve la deshidratación, lo que finalmente causa que las personas beban más agua y se genere una alta acumulación de fluoruros (38). Finalmente, el estado nutricional es determinante para la aparición de fluorosis (41); estudios determinan que un factor de riesgo era un estado nutricional inadecuado (22,42). Micronutrientes como el calcio y la vitamina D han probado ser efectivos en reducir la absorción de flúor; los productos lácteos también han presentado evidencia de reducir la absorción de flúor en el tracto gastrointestinal (43). ...
Introducción: El flúor en agua potable ha demostrado ser efectivo contra las caries, sin embargo, una alta exposición a fluoruros es una de las principales causas de fluorosis dental en niños. Objetivo: El objetivo de este estudio fue determinar la concentración de flúor en agua de consumo para conocer si constituye un factor de riesgo para la fluorosis dental en niños del sector rural de Cuenca-Ecuador. Metodos: El muestreo se realizó en nueve parroquias rurales del cantón, en tres puntos de red: (1) tanques de captación, (2) tanques de almacenamiento del sistema de potabilización, y (3) el sistema de distribución en escuelas, considerando el periodo estacional de verano (época sequía) o invierno (época lluviosa). Las determinaciones de flúor se realizaron con la técnica del ion selectivo. Resultados: Los resultados indicaron que todas las muestras estuvieron debajo de la concentración de 1.5 mg/L (límite OMS), en los rangos: 0,0–0,0565 mg/L en los tanques de captación; 0,0–0,0440 mg/L en los tanques de almacenamiento; y 0,0–0,0525 mg/L en los sistemas de distribución de las instituciones educativas. La prueba ANOVA indicó que las variables parroquias y estación influyen en la concentración de fluoruros (valor p<0.01). Conclusiones: La concentración de flúor en el agua es menor a la concentración límites permitida, lo anterior permite descartar al agua potable como causa para el desarrollo de fluorosis dental. Los hallazgos presentados respaldan el investigar otros factores de riesgo como condiciones geográficas, alimentación, dentífricos, etc., debido a que la fluorosis dental constituye un problema multifactorial.
... In Ethiopia, where defluoridation requires costly infrastructure, more than 14 million individuals, mainly in the Rift Valley, are affected by fluorosis [2][3][4][5]. Research suggests that the adverse effects of fluoride (F) can be reversed or lessened by providing sufficient food intake of protein, calcium (Ca), anti-oxidants, and vitamin D [6][7][8]. Of these, Ca is the most studied by ecological studies [8][9][10][11]. However, there have been no intervention studies of Ca to mitigate fluorosis at the community level in Ethiopia. ...
Dietary calcium binds Fluoride (F), thus preventing excess F absorption. We aimed to assess the efficacy of supplementing calcium-containing Eggshell Powder (ESP) on F absorption using urine F excretion and on fluorosis symptoms. In total, 82 women (41 Intervention Group, IG; 41 Control Group, CG) were recruited; overall, 39 in each group completed the trial. Morning spot urine was collected before (baseline, BL) and after (endline, EL) the intervention that was 6-months daily supplementation with 2.4 g ESP (providing ~1000 mg of calcium). Dental, skeletal, and non-skeletal fluorosis assessments was carried out at BL and, except for dental, at EL. Relative risk (RR) and linear generalized estimating equation were used to compare outcomes between groups. At BL, urinary F excretion in the IG and CG groups was similar, ~10 mg/L. At EL, urinary F excretion in IG women was six-fold lower (β = −6.1 (95% CI: −7.1, −5.1)) compared to CG. The risk of developing skeletal and non-skeletal fluorosis were significantly (p < 0.001) reduced in the intervention group. A significant reduction in urinary F excretion and reduction in many fluorosis symptoms were observed among women supplemented with calcium-containing ESP, thus providing evidence for using this dietary calcium source for mitigation of fluorosis. Clinical trials registration: NCT03355222.
... The evident in the literature confirms that people under poor nutritional status were highly susceptible to dental fluorosis risk (Akuno et al., 2019;Vasant and NarasimhacharyaAmaravadi, 2013;Choubisa et al., 2009;Yoder et al., 1998;Goodman and Rose, 1991;Chen et al., 1997). A recent clinical study conducted at high altitude area in India evidenced that the children under poor nutrition status are severely affected with dental fluorosis than the children under normal nutrition status residing in the same region (Khandare et al., 2017). ...
Many scientific reports emphasized that the extent of prevalence and severity of dental fluorosis is higher among the people residing at high altitude regions than lower altitudes, even though they are exposed to drinking water with similar or less fluoride levels. This review reports various factors which enhance the risk of prevalence and severity of dental fluorosis at high altitude regions through different pathways. Especially, this review focused on ecological, physiological, biochemical and dietary factors as well as to identify potential key areas to implement further research on control of dental fluorosis risk at high altitude regions. In addition, by considering the pathways of risks, suitable remedial measures are also recommended in this review to manage the dental fluorosis risk at higher altitude regions.
... In contrast to the results of current study, Rogalska et al. [27] reported that glucose concentration did not significantly differ among the experimental groups that treated with sodium fluoride compared with control, and also disagrees with Vasant and Narasimhacharya [28]; Thangapandiyan and Miltonprabu [11]; Alol, [29] who all found a significant increase in serum glucose concentration in NaF treated groups compared with those of control. ...
This study was conducted to investigate the role of calcium chloride and / or vitamin C in protecting against the effect of deterioration in liver function and structure resulting from exposure to sodium fluoride. Fifty adult male rats were used, which divided randomly into five equal groups, the first group: The animals of this group served as control group administrated distilled water orally by gavage. Second group: administrated NaF (5.2mg/kg.bw/day) orally by gavage. Third group: administrated NaF (5.2mg/kg.bw/day) + Calcium Chloride (20mg/kg.bw/day) orally by gavage. Fourth group: administrated NaF (5.2mg/kg.bw/day) + Vitamin C (100mg/kg.bw/day) orally by gavage. Fifth group: administrated NaF (5.2mg/kg.bw/day) + Calcium Chloride (20mg/kg.bw/day) + Vitamin C (100mg/kg.bw/day) orally by gavage. The treatment continued for 45 days. At the end of the experiment, animals were sacrificed under anesthesia. Blood samples were taken and the serum was separated for the study of the liver enzymes and glucose level, and tissue samples of the liver were taken for histological changes. The study showed a significant elevation in serum concentration of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphates (ALP) enzymes and a significant reduction in glucose concentrations were recorded in NaF treated group compared with the control. Moreover a significant degreesof improvement was recorded in above cited parameters in all treated groups compared with NaF group with some variation between them. Histopathological study revealed that liver section of NaF treated group showed destruction of hepatocytes architecture, several areas of necrosis, disrupted sinusoid and 288 vacuolation.Significant improvement was observed in hepatic tissue of all treatments compared to control group.
... The observed lower serum insulin levels in Fluoride intoxication might be due to associated liver damage [Tokar 1992]. Liver damage has also been observed by Vasant and Narasimhacharya [2013a] who state "Exposure to fluoride through drinking water not only significantly increased plasma glucose and lipid profiles, but also elevated both hepatic and renal lipid peroxidation, hepatic lipid profiles and G-6-Pase activity with a reduction in plasma HDL-C, hepatic glycogen content, hexokinase activity and antioxidant status". ...
Experts in endocrinology have shown that Fluoride causes Diabetes and Obesity. This review assembles the wealth of science that shows how Fluoride damages the organs that generate or use Insulin to control Glucose metabolism and the crucial involvement of other hormone systems.
... [40] Drinking fluoridated water not only increases plasma glucose and lipid profile levels, but also elevates hepatic and renal lipid peroxidation. [41] 6.9 Impact of Fluoride on renal system ...
... These data were accompanied by less and more fluoride urinary excretion, respectively (Lakshmaiah and Srikantia, 1977). Also, a multigrain diet enriched with protein was showed to attenuate fluorosis toxicity (Vasant and Amaravadi, 2013). ...
Fluoride is widely used as an anticariogenic agent but excessive ingestion may lead to systemic toxicity. Its biological effects are dependent on the amount, time of exposure and the metabolic handling of ingested fluoride. After being ingested, fluoride is first absorbed in the stomach, followed by its distribution through soft and hard tissues and urine excretion. These events occur in a pH-dependent manner because the coefficient of permeability of lipid bilayer membranes to hydrogen fluoride is much higher than that of ionic fluoride. Therefore, fluoride drives through cell membranes as HF, in response to a pH gradient between adjacent compartments, going from more acidic to more alkaline compartments. The fluoride plasma peak is quickly reached after ingestion, as result of a rapid pH-dependent absorption in the stomach. The small intestine also contributes to fluoride absorption but this event is not pH dependent. Plasma fluoride levels are rapidly decreased mainly due to fluoride uptake in hard tissues and renal excretion, while the nonabsorbed fluoride is excreted in feces. Thus, plasma fluoride concentration is a result of the relation between the levels of ingestion, and metabolism accounted by its deposition in calcified tissues and excretion. Additionally, the latter is modified by several factors that will be discussed in detail in this chapter.
... The observed lower serum insulin levels in Fluoride intoxication might be due to associated liver damage [Tokar 1992]. Liver damage has also been observed by Vasant and Narasimhacharya [2013a] who state "Exposure to fluoride through drinking water not only significantly increased plasma glucose and lipid profiles, but also elevated both hepatic and renal lipid peroxidation, hepatic lipid profiles and G-6-Pase activity with a reduction in plasma HDL-C, hepatic glycogen content, hexokinase activity and antioxidant status". ...
This brief literature review and bibliography presents evidence that Fluoride, through fluoridation of public drinking water, causes Diabetes as well as injury to existing diabetics.
... Additionally, plant metabolites such as a 43-kDa protein isolated from Cajanus indicus, quercetin and curcumin have been shown to ameliorate fluoride-induced oxidative stress and improve the functions of liver, kidney and erythrocytes [13][14][15][16]. We recently reported the beneficial effects of seasonally available edible fruits (Limonia acidissima, Mangifera indica, Emblica officinalis) as dietary supplements/adjuncts and high-protein diets on various metabolic parameters associated with fluoride-induced alterations in body metabolism [17][18][19][20][21]. ...
Objectives
Fluoride is a serious health hazard across several nations, and chronic intake of fluoride deranges the carbohydrate, lipid and antioxidant metabolism in general. As there are limited remedial measures to prevent fluorosis, we investigated the role of tamarind leaf as a food supplement in restoration of carbohydrate, lipid and antioxidant metabolism in fluoride-exposed albino rats.
Methods
Albino rats were exposed to fluoride (100 ppm sodium fluoride) through drinking water and fed diet supplemented with tamarind leaf powder (2.5, 5 and 10 g %) for 4 weeks. Carbohydrate, lipid and antioxidant profiles were investigated in both controls and fluoride-exposed animals.
Results
While 4-week exposure to fluoride elevated plasma glucose and lipid profiles, simulating diabetic and hyperlipidaemic conditions, the antioxidant defence mechanisms of fluoride-exposed rats were compromised, with elevation and decline in lipid peroxidation and high-density lipoprotein (HDL)-cholesterol, respectively. When the diet was supplemented with tender tamarind leaves (used in southern India as a replacement for tamarind or other sour food ingredients), significant improvements in carbohydrate and lipid profiles occurred as evidenced by decreased plasma glucose and lipid levels, lipid peroxidation, increased hepatic glycogen content, hexokinase activity and cholesterol excretion, with simultaneous improvement in antioxidant profiles of both hepatic and renal tissues.
Conclusions
These findings are significant in view of the need for cost-effective approaches to tackle fluorosis as an environmental hazard and use of food supplements as ameliorative measures.
Introduction:
The aim of the current study was to investigate associations between dental fluorosis in children living in low socioeconomic areas in Mexico, and fluoride concentrations in tap water, fluoride concentrations and in bottled water, and body mass index (BMI).
Methods:
A cross-sectional study involving 585 schoolchildren aged 8-12 years was conducted in communities in a southern state of Mexico with >0.7 parts per million (ppm) fluoride in the groundwater. The Thylstrup and Fejerskov index (TFI) was used to evaluate dental fluorosis, and the World Health Organization growth standards were used to calculate age-adjusted and sex-adjusted BMI Z-scores. A BMI Z-score ≤ -1 SD was used as the cut-off point for thinness, and multiple logistic regression models for dental fluorosis (TFI ≥ 4) were constructed.
Results:
The mean fluoride concentration in tap water was 1.39 ppm (SD 0.66), and the mean fluoride concentration in bottled water was 0.32 ppm (SD 0.23). Eighty-four children (14.39%) had a BMI Z-score ≤ -1 SD. More than half (56.1%) of the children presented with dental fluorosis in TFI categories ≥ 4. Children living in areas with higher fluoride concentrations in the tap water [odds ratio (OR) 1.57, p = 0.002] and bottled water (OR 3.03, p < .001) were more likely to have dental fluorosis in the severe categories (TFI ≥ 4). BMI Z-score was associated with the probability of dental fluorosis (TFI ≥ 4; OR 2.11, p < 0.001), and the effect size was 29.3%.
Discussion:
A low BMI Z-score was associated with a higher prevalence of dental fluorosis in the severe category. Awareness of the fluoride concentrations in bottled water may help prevent dental fluorosis, particularly in children exposed to several high fluoride content sources. Children with a low BMI may be more vulnerable to dental fluorosis.
The present study investigated the mitigative effect of Vitex negundo against sodium fluoride (NaF) induced cardio and nephrotoxicity. The hydroalcoholic extract of Vitex negundo leaves (HAEVNL) was prepared by the maceration method. Group I, Group II, and Group III served as normal, toxic, and plant control groups in the treatment schedule. Group IV and V (200 and 400 mg/kg b.wt, p.o) served as treatment groups. Group II, IV, and V treated with NaF (100ppm) through drinking water for 4 weeks. Cardiac and kidney parameters such as LDH, CK-MB, Lipid profile, Creatinine, Urea, and Uric acid were estimated. The heart and kidney tissues LPO, GSH, SOD, and CAT levels and histopathological studies were performed. Phytochemical investigation showed the alkaloids, saponins, phytosterols, flavonoids, phenols, and tannins. Rats administered with NaF have demonstrated a significant rise in the LDH, CK-MB, TC, TG, LDL-C, VLDL-C, Creatinine, Urea, and Uric acid. Tissue LPO levels increased while there was a significant decrease in serum HDL-C and tissue SOD, GSH, and CAT levels. Treatment with HAEVNL showed effective recovery against NaF-induced cardio and nephrotoxicity. The histopathological evaluation also added to the benefits of the Vitex negundo leaves. The study concluded that Vitex negundo leaf extract showed a significant antioxidant and mitigative effect against fluoride- induced cardio and nephrotoxicity in rats.
Fluorosis caused by consumption of dark tea is a major public health problem in the western part of China. In this study, the effects of milk powder, butter, and table salt on the bioavailability of the fluoride in an infusion of dark tea were investigated in a rat model. These substances were examined for their potential as dietary interventions to reduce the risk of tea-induced fluorosis. Fluoride was less bioavailable from the dark tea infusion than from a NaF solution. The addition of milk powder significantly decreased the amount of fluoride absorbed from the dark tea infusion and increased the amount of fluoride in fecal excretion. While butter had a limited effect on fluoride bioavailability, it prolonged the fluoride absorption period. The addition of 4 mg/mL table salt significantly increased the bioavailability of fluoride in the dark tea infusion. The addition of different flavor augmentations to a dark tea infusion had different effects on fluoride bioavailability. Therefore, dietary intervention may be a novel strategy for reducing fluorosis risk.
Sodium fluoride has a very negative effect on the society because it is used in many aspects of life so this problem was highlighted for the purpose of finding suitable solutions. The current study was conducted in the Animal House of the Faculty of Veterinary Medicine / University of Basrah to evaluate the role of calcium chloride and vitamin C each one alone or both together in some physiological parameters and histological changes for male rats exposed to sodium fluoride (NaF).
Fifty adult male rats were used in the study, which are divided randomly into five equal groups as follows: the first group (control group) in which rats were given (0.2 ml) distilled water orally by gavage, the second group (NaF) the animals of this group were given NaF (5.2 mg/kg b.w/day). 3rd (NaF+CaCl2) and 4th (NaF+ Vitamin C) groups were given CaCl2 (20 mg/kg b.w/day) or Vitamin C (100 mg/kg b.w/day) respectively in addition to NaF. The 5th group (NaF+ CaCl2 +Vitamin C) the animals of this group were given similar doses to that in previous groups.
The experiment continued for 45 days. At the end of the experiment, the animals were sacrificed under anesthesia. Blood samples were taken for studying hormonal and biochemical parameters. Tissue samples of the thyroid, liver, kidneys, testicles, and femur bone were used for studying histological changes. Epididymal sperm characteristics also studied. The study showed the following results:
A significant decrease in final body weight, body weight gain, tri-iodothyronine (T3), thyroxin (T4) and testosterone hormone concentrations, serum concentration of calcium and phosphorous, high density lipoproteins cholesterol (HDL-C), epididymal sperm count and percentage of sperm motility were recorded in NaF treated group compared with control group.
A significant increase in relative weight of kidneys, thyroid stimulation hormone (TSH), follicle stimulating hormone (FSH) and Luteinizing hormone (LH), serum concentration of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphates (ALP), serum concentration of triglyceride(TG), total cholesterol(TC), low density lipoproteins(LDL-C) and very low density lipoproteins (VLDL-C), serum creatinine and urea, percentage of dead and abnormal sperms were recorded in NaF treated group compared with control.
Finally the histopathological results indicated that NaF causes proliferation in thyroid follicles, characterized by formation of large number of small follicles in thyroid gland. Destruction of hepatocytes architecture, several areas of necrosis, disrupted sinusoid and vacuolation. Enlarged glomerulus, destruction of cuboidal epithelium of renal tubules. Severe suppression of spermatogenesis, vacuolation and degeneration of spermatogonia and primary spermatocytes were observed. Reduction in ostieocytes density.
Conclusion: Exposure of adult male rats to NaF resulted in significant changes in the functional parameters of thyroid, liver, kidney and testes accompanied with histopathological changes. Administration of calcium and/or Vitamin C reduces most of NaF induced changes, different degrees of amelioration were observed, however no improvement was observed in the kidney section of NaF + CaCl2 group compared with NaF group.
In 2017 the Australian National Health and Medical Research Council (NHMRC) released a draft information paper on the health effects of water Fluoridation that completely ignored thousands of peer-reviewed scientific publications regarding Fluoride toxicity, by using contrived exclusion criteria and time limits. Similar tactics were employed by the NHMRC in its Fluoridation review published in 2007. This submission, one of the 32 made public, formally records some of the science that has been deliberately ignored.
The relationship between fluorosis and the lifestyle of adult residents of areas in which fluorosis is endemic was evaluated. A cross-sectional and case-control analysis was performed to study 289 villagers living in fluorosis endemic areas who drank the local water. Subjects were divided into skeletal fluorosis and non-skeletal fluorosis groups according to whether they were afflicted with skeletal fluorosis. A semi-quantitative food frequency questionnaire, homemade lifestyle questionnaires, and general characteristics were analyzed. The factors that affected the occurrence of skeletal fluorosis were determined by generalized estimating equations. Our results showed that protective factors against skeletal fluorosis included drinking boiled water, storing water in a ceramic tank, and ingesting fruits, vitamin A, thiamine, and folic acid. Risk factors for skeletal fluorosis were overweight status and obesity, drinking tea, drinking water without storage, and ingestion of oils, fats, and phosphorus. Our results demonstrate that skeletal fluorosis has a close relationship with lifestyle.
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Abstract The aim of this study was to establish the effects of fluoride on lipid metabolism and attendant inflammatory response by exposing rats to 50 mg L-1 and 100 mg L-1 of fluoride through drinking water for seven weeks. Both concentrations led to hypercholesterolemia while the 100 mg L-1 concentration induced hypertriglyceridaemia. High density lipoprotein (HDL) cholesterol levels dropped in the exposed rats while interleukin 2 (IL-2) increased more than 1.5-fold (p<0.05) and IL-6 and plasma TNF-α more than 2.5 fold (p<0.05). Fluoride-exposed rats also had significantly higher levels of liver malondialdehyde (MDA) and plasma lipid hydroperoxide (LOOH) but lower plasma paraoxonase (PON1) activity. Oxidative stress indices correlated with pro-inflammatory cytokines and plasma cholesterol. In contrast, proinflammatory cytokines inversely correlated with plasma triglyceride, HDL cholesterol and PON1. Our results suggest that the association between fluoride exposure with cardiovascular diseases may be related to its ability to disturb lipid homeostasis, and trigger pro-inflammatory cytokines and oxidative stress.
AIM: The mitigative effects of L. fruit powder as a dietary supplement in fluoride toxicity were investigated with reference to tissue lipid peroxidation and antioxidant metabolism. METHODS: Fluoride toxicity was induced in laboratory rats through drinking water (100 ppm sodium fluoride) and the rats were fed diet supplemented with mango fruit powder with three different doses (2.5, 5 and 10 g %) for 30 days. RESULT: Exposure to fluoride resulted in significant elevation of hepatic and renal tissue lipid peroxidation with a reduction in antioxidant profiles. Administration of mango fruit powder reduced both hepatic and renal tissue lipid peroxidation, with a significant increase in antioxidant profiles (TAA, SOD, CAT, GSH and GPX). CONCLUSION: fruit possesses considerable antiperoxidative and antioxidant potential to mitigate the fluoride toxicity. ÖZET GİRİŞ: Besin takviyesi olarak L. meyve tozunun Florür toksisitesinde hafifletici etkileri, doku lipit peroksidasyonu ve antioksidan metabolizma baz alınarak araştırılmıştır. YÖNTEM: Florür toksisitesi, içme suyu sayesinde (100 ppm sodyum florür) laboratuar sıçanlarında oluşturuldu ve sıçanlar 30 gün süresince üç farklı dozda (%2.5, %5 ve %10 gram) mango meyve tozu ile takviye olarak beslendi. BULGULAR: Florüre maruz kalım, antioksidan profillerde bir azalma ile birlikte hepatik ve renal lipit peroksidasyonunda belirgin yükselmeye neden oldu. Mango meyve tozunun verilmesi, antioksidan profillerde (TAA, SOD, CAT, GSH ve GPX) belirgin bir artışla birlikte, hepatik ve renal doku lipit peroksidasyonunu azalttı. SONUÇ: meyvesi, florür toksisitesini hafifletmede dikkat çekici antiperoksidatif ve antioksidan potansiyele sahiptir.
Background:
Limonia fruit pulp is edible and used in a number of food preparations. This fruit is also used as a folk medicine to treat various ailments and reportedly possesses antihyperglycaemic and antihyperlipidaemic activities. The purpose of the present study was to examine the potential of Limonia acidissima L. (LA) fruit pulp in regulating the carbohydrate and lipid profiles in fluoride-exposed rats.
Results:
Exposure to fluoride (100 mg l⁻¹ NaF) resulted in significant increases in plasma and hepatic carbohydrate and lipid profiles. Administration of LA fruit powder (2.5, 5 and 10 g kg⁻¹) in the diet for 4 weeks resulted in significant decreases in plasma glucose and lipid profiles and hepatic glucose-6-phosphatase activity and significant increases in hepatic glycogen content and hexokinase activity and plasma high-density lipoprotein cholesterol. Phytochemical analysis of the LA fruit pulp revealed the presence of fibres, phytosterols, saponins, polyphenols, flavonoids and ascorbic acid.
Conclusion:
Consumption of LA fruit pulp is beneficial in controlling hyperglycaemia and hyperlipidaemia in fluoride-induced toxicity. Since fibres, phytosterols, saponins, polyphenols, flavonoids and total ascorbic acid are known to influence both carbohydrate and lipid metabolisms, the decline in carbohydrate and lipid levels in LA-administered fluoride-exposed rats could be attributed to the phytoconstituents of the fruit.
: To evaluate the protective effect of tamarind pulp against fluoride (F)-induced oxidative stress in the liver, adult female Wistar rats were treated daily for 45 days with sodium fluoride (300 ppm NaF = 136.7 ppm fluoride ion) in drinking water, alone or in combination with tamarind pulp (20 mg/kg bw by oral intubation). Malondialdehyde (MDA), antioxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and ascorbic acid level in the liver, and levels of calcium and F, plus activities of aspartate transaminase (AST) and alanine transaminase (ALT) in serum were determined 24 hr after the last treatment. In the NaF-treated animals, a significant increase in MDA content and a concomitant decrease in antioxidant enzyme activities of SOD, CAT, GSH-Px, and the ascorbic acid level in liver and increased activities of AST and ALT, and increased calcium and F concentrations in serum were observed. Administration of tamarind pulp together with NaF produced significant amelioration in all parameters studied, indicating that tamarind pulp is able to prevent free radical induced oxidative stress by F, attributable to its antioxidant property. It is concluded that tamarind pulp may be useful to prevent the oxidative damage caused by consumption of excessive amounts of F.
: The effects on free radical toxicity in the liver of male mice from their ingestion of protein enriched and protein deficient diets along with 5, 10, and 20 mg NaF/kg body wt were investigated. Feeding a protein deficient diet with any of the three NaF doses for 30 days resulted in a significant decrease in levels of glutathione and reduced ascorbic acid as well as activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase in the liver. On the other hand, significant increases in lipid peroxides (LPO), dehydroascorbic acid (DHA), and fluoride levels were observed. The increase in total ascorbic acid (TAA) levels was less significant. These changes also occurred in mice fed the standard control protein diet plus the same doses of NaF. By contrast, when mice were fed a protein enriched diet along with NaF, none of the liver parameters studied were affected but were essentially the same as in mice fed the control protein diet without added fluoride. These studies indicate that dietary protein supplementation has a beneficial effect on liver function and is conducive to recovery from fluoride toxicity. The results also indicate the importance of adequate protein in the diet especially in developing countries where dietary protein deficiency and malnutrition are often present.
: The effects of ingestion of protein deficient or protein supplemented diets with or without sodium fluoride (NaF, 5, 10, and 20 mg/kg body wt) were studied on sperm function in mice and compared with effects on mice fed a control (standard) protein diet + NaF in the above three dose levels for 30 days. Ingestion of the protein deficient diet together with the three dose levels of NaF caused a significant decrease in sperm motility, sperm count, sperm viability, fertility rate, sperm mitochondrial activity index (SMAI), number of normal spermatozoa, and hyaluronidase activity. However, DNA integrity, assessed by acridine orange fluorescence staining, and total acrosin levels, for acrosome integrity, were comparatively less affected. The control protein diet plus the three dose levels of NaF also caused significant alterations in all these parameters as compared to control Group I. However, mice fed a protein supplemented diet with or without the three doses of NaF did not manifest any changes, and the above parameters in them were almost the same as in control Group I. The decrease in sperm motility appears to be related to decline in SMAI and abnormal sperm counts. The significant decrease in sperm viability along with the above parameters would be expected to affect fertility, whereas inhibition of hyaluronidase and to some extent of acrosin could affect fertilizing capacity of the sperm. The results reveal that dietary factors such as increased protein intake can be especially valuable in curbing fluoride fertility toxicity.
: Adult male Swiss strain mice were fed a control protein diet, a protein deficient diet, and a protein enriched diet with and without sodium fluoride (5, 10, and 20 mg NaF/kg body wt for 30 days) to study the effects on fluoride induced oxidative stress in the testis. Ingestion of the protein deficient diet together with NaF resulted in a significant decrease in the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) as well as in levels of reduced ascorbic acid (RAA) and glutathione (GSH). By contrast, the serum and testis levels of lipid peroxides (LPO), total ascorbic acid (TAA), dehydroascorbic acid (DHA), and fluoride increased significantly compared to the controls. Similar results were obtained in mice with the control protein diet plus the same doses of NaF. However, in mice fed the protein enriched diet along with the same doses of NaF, essentially no change in these parameters occurred, which were almost the same as in the controls. These results clearly indicate that protein supplementation in the diet is conducive to overcoming fluoride induced oxidative stress in mice testis and that analogous dietary improvement could play a major role in overcoming human fluoride toxicity in endemic areas.
The effect of tamarind ingestion on fluoride retention was studied in three groups of dogs - control (Group I), fluoride-supplemented (Group II), and fluoride and tamarind-supplemented diets (Group III). The urinary excre- tion of fluoride was significantly higher in Group II (2.45 ± 0.39 mg F/day) and Group III (3.78 ± 0.35 mg F/day) as compared to Group I (0.205 ± 0.21 mgF/ day). The difference between Group II and III was also significant. The femur fluoride content of Group II animals (4.0 ± 0.67mg F/gm ash) was significantly higher as compared to that of Group III (2.0 ± 0.52 mg F/gm ash) suggesting a beneficial effect of tamarind ingestion on fluoride retention and toxicity. There were no significant differences in hematological parameters between the groups, although hemoglobin levels and packed cell volume tended to be lower in Group III as compared to Group I. Histopathological study showed that except in kidneys where congestion and tubular changes were greater in experimental groups as compared to control, all other organs were compara- ble between the groups.
: Fourteen-week-old male Wistar FL strain rats were administered sodium fluoride in a single intraperitoneal dose (35 mg NaF/kg bw) and after 90 min were fatally anesthetized. In a separate experiment, four-week-old male rats of the same strain were given fluoride in their drinking water (50 or 100 mg F – /L) for four months and then anesthetized. Both experiments produced hyperglycemia, accompanied by a statistically significant increase in the concentrations of fluoride in the blood serum. Hypertriacylglycerolemia also occurred in the long-term intoxication experiment, thereby indicating disturbances of lipid metabolism under the influence of NaF, which are similar to those observed in diabetes mellitus or in starvation.
Ascorbic acid is an important micronutrient necessary for a significant number of metabolic reactions in humans and other primates. It is a strong reducing agent involved in reduction reaction and it is structurally related to glucose. Experimental and epidemiological studies have documented the biochemical, physiological and therapeutic roles of ascorbic acid. It is an essential water-soluble antioxidant vitamin derived from exogenous source; thus its role in human health is worthy to be considered particularly because of the current global economic trend. The biochemical, physiological and therapeutic roles of ascorbic acid is reviewed, providing further insights into the role of ascorbic acid in biological functions.
To examine its antidiabetic potential in fluoride (F) intoxicated rats, the anti-diabetic drug glibenclamide was administered for 4 weeks to diabetic rats and to diabetic rats exposed to 100 mg NaF/L in the drinking water. In the F treated rats there was a significant reduction in plasma glucose, plasma and hepatic total lipids, cholesterol, triglycerides and plasma low-density lipoproteins (LDL), VLDLcholesterol, and atherogenic index accompanied by significant increases in HDLcholesterol, FRAP (ferric reducing ability of plasma) and protein content. Furthermore, significant decreases in SGOT (serum glutamate oxaloacetate transaminase), SGPT (serum glutamate pyruvate transaminase), alkaline and acid phosphatase (ALP and ACP), and glucose-6-phosphatase (G-6-Pase) were observed in these F-treated animals. In addition, administration of the drug decreased hepatic and renal lipid peroxidation with a concomitant increase in total ascorbic acid (TAA), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPX), and FRAP levels in the F-treated animals. It is proposed that glibenclamide acts at two levels: (i) at pancreatic islets for increased release of insulin from surviving β cells, (ii) at the target sites, e.g., hepatic tissue to improve glucose uptake leading to an improvement in the activities of hepatic and renal TAA, SOD, GSH, GPX, and reduction in lipid peroxidation. Glibenclamide may therefore be useful for treatment of diabetes in F endemic areas.
We report an investigation into the antioxidative effect of Limonia acidissima (LA) fruit powder on fluoride-induced hepatic and renal oxidative stress in rats administered 100 ppm NaF (45.2 ppm F ion) in their drinking water. LA fruit powder was mixed with the diet at 2.5, 5.0, and 10.0 gram percent levels for four weeks, after which the antioxidant status of the liver and kidneys was assessed by measuring the levels of lipid peroxidation by thiobarbituric reactive substances (TBARS), total ascorbic acid (TAA), and reduced glutathione (GsH), along with decreased activities of catalase (CAT), superoxide dismutatse (SOD), and glutathione peroxidase (GPx). LA produced a significant (p <0.05) dose-dependent decrease in the levels of TAA and GsH, and also the activities of CAT, SOD, and GPx, along with an elevation in the TBARS concentration. These results indicate that LA fruit powder has considerable anti-oxidant activity as a nutritional supplement and offers protection against F-induced hepatic and renal oxidative stress.
Aqueous extracts of T. indica fruit pulp (100 mg/kg body weight) and M. oleifera seeds (50 mg/kg body wight) orally once daily for 90 days lowered plasma fluoride concentrations in rabbits receiving fluorinated drinking water (200 mg NaF/ Liter water). Cortical indices and metaphysial width in animals receiving extracts also revealed beneficial effects of plant extracts. Changes in plasma biochemistry suggested less hepatic and renal damages in animals receiving plant extracts along with fluorinated water in comparison to that receiving fluorinated water alone. Preliminary results revealed these plant extracts have some potential to mitigate fluoride toxicity.
Fluorosis is a serious public health problem in many parts of the world. As in the case of many chronic degenerative diseases, increased production of reactive oxygen species has been considered to play an important role, even in the pathogenesis of chronic fluoride toxicity. Black berry is closely linked to its protective properties against free radical attack. Therefore, the aim of this study was to demonstrate the role of black berry juice (BBJ) in decreasing the hepatotoxicity and oxidative stress of sodium fluoride (NaF). Results showed that NaF caused elevation in liver TBARS and nitric oxide (NO), and reduction in superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC) and glutathione (GSH). Plasma transaminases (AST and ALT), creatine kinase (CK), lactate dehydrogenase (LDH), total lipids (TL), cholesterol, triglycerides (TG), and low density lipoprotein-cholesterol (LDL-c) were increased, while high density lipoprotein-cholesterol (HDL-c) was decreased. On the other hand, BBJ reduced NaF-induced TBARS, NO, TL, cholesterol, TG, LDL-c, AST, ALT, CK and LD. Moreover, it ameliorated NaF-induced decrease in SOD, CAT, GSH, TAC and HDL-c. Therefore, the present results revealed that BBJ has a protective effect against NaF-induced hepatotoxicity by antagonizing the free radicals generation and enhancement of the antioxidant defence mechanisms.
Plant foods are important due to their antioxidant activity (AOA) attributed to the phenolics which are known to protect organisms against harmful effects of oxygen radicals. However, information on antioxidant activity of Indian plant foods is scanty. Therefore, the present study evaluated the AOA of cereals, millets, pulses and legumes, commonly consumed in India and assessed the relationship with their total phenolic content (TPC). AOA was assessed by DPPH (2,2-Diphenyl-1-picryl hydrazyl) radical scavenging assay, ferric reducing antioxidant power (FRAP) assay and reducing power. DPPH scavenging activity ranged from 0.24 and 1.73 mg/g, whereas FRAP ranged from 16.21 to 471.71 micromoles/g. Finger millet (Eleusine cora cana) and Rajmah (Phaseolus vulgaris) had the highest FRAP 471.71, 372.76 and DPPH scavenging activity 1.73, 1.07. Similar trends were observed with reducing power. Among cereals and legumes, Finger millet (Ragi) and black gram dhal (Phaseolus mungo Roxb) had the highest TPC, the values being 373 and 418 mg/100 g respectively, while rice (Oryza sativa) and green gram dhal (Phaseolus aureus Roxb) showed the least (47.6 and 62.4 mg/100 g). In the present study, FRAP (r = 0.91) and reducing power (r = 0.90) showed significant correlation with TPC in cereals and millets, but not in pulses and legumes. The results suggest that TPC contributes significantly to the AOA of Indian cereals and millets.
The distribution of catalase and superoxide dismutase has been examined in various micro-organisms. Strict anaerobes exhibited no superoxide dismutase and, generally, no catalase activity. All aerobic organisms containing cytochrome systems were found to contain both superoxide dismutase and catalase. Aerotolerant anaerobes, which survive exposure to air and metabolize oxygen to a limited extent but do not contain cytochrome systems, were found to be devoid of catalase activity but did exhibit superoxide dismutase activity. This distribution is consistent with the proposal that the prime physiological function of superoxide dismutase is protection of oxygen-metabolizing organisms against the potentially detrimental effects of the superoxide free radical, a biologically produced intermediate resulting from the univalent reduction of molecular oxygen.
To determine glutathione peroxidase reliably, some factors of potential pitfall have to be considered, for example, enzymatic side reactions of substrates (especially when crude tissue samples are assayed), high and variable spontaneous reaction rates of substrates, and the peculiar kinetics of the enzyme itself. With the best documented example, the enzyme of bovine red blood cells, ping-pong kinetics with infinite limiting maximum velocities, and Michaelis constants have been established. This means that the generally recommended conditions for determination of enzyme activity––that is, “saturating” concentrations of all substrates, cannot possibly be fulfilled. In consequence, compromises are inevitable in the choice of substrate concentration for the assay and in the definition of the unit of activity. Fixed-time assay measuring H2O2 consumption and continuous monitoring of Glutathione disulfide (GSSG) formation are cited here. The main differences between the assay procedure described and those proposed by others are listed in the chapter. To compare the results obtained by different procedures, appropriate empirical converting factors are also given.
The combustion of high fluoride-content coal as an energy resource for heating, cooking, and food drying is a major exhaust emission source of suspended particulate matter and fluoride. High concentrations of these pollutants have been observed in indoor air of coal-burning families in some rural areas in China. Because airborne fluoride has serious toxicological properties, fluoride pollution in indoor air and the prevalence of fluorosis have been analyzed in a fluorosis area and a healthy nonfluorosis area in China and in a rural area in Japan. For human health, fluoride in indoor air has not only been directly inhaled by residents but also has been absorbed in stored food such as corn, chilies, and potatoes. In the fluorosis area in China, concentrations of urinary fluoride in the residents have been much higher than in the nonfluorosis area in China and in the rural area in Japan. In the fluorosis area, almost all elementary and junior high school students 10-15 years of age had dental fluorosis. Osteosclerosis in the skeletal fluorosis patients was very serious. Urinary deoxypyridinoline in rural residents in China was much higher than in rural residents in Japan. Data suggest that bone resorption was extremely stimulated in the residents in China and that fluoride may stimulate both bone resorption and bone formation. Because indoor fluoride from combustion of coal is easily absorbed in stored food and because food consumption is a main source of fluoride exposure, it is necessary to reduce airborne fluoride and food contamination to prevent serious fluorosis in China.
To evaluate the effect of tamarind (Tamarindus indicus) ingestion on excretion of fluoride in school children.
Randomized, diet-control study.
Twenty healthy boys were included and 18 of them completed the study.
Each subject consumed 10 g tamarind daily with lunch for 18 days at the social welfare boys' hostel. The nutrient composition of the daily diet was constant throughout the experimental period.
Tamarind intake led to significant increase (P<0.001) in the excretion of fluoride in 24 h urine (4.8+/-0.22 mg/day) as compared to excretion on control diet (3.5+/-0.22 mg/day). However, excretion of magnesium and zinc decreased significantly (7.11+/-1.48 mg of Mg and 252.88+/-12.84 microg of Zn per day on tamarind diet as compared to 23.39+/-3.68 mg of Mg and 331.78+/-35.31 microg Zn per day on control diet). Excretion of calcium and phosphorous were not significantly different while creatinine excretion decreased with tamarind intake (225.66+/-81 mg creatinine/day with tamarind and 294.5+/-78.76 mg creatinine/day without tamarind).
Tamarind intake is likely to help in delaying progression of fluorosis by enhancing urinary excretion of fluoride.
The effect of nutrition on the teeth of goats consuming industrial fluoride-contaminated grass during the dry grass season was studied in three groups of ten goats each, pastured in the same area of fluoride pollution. The control group diet was not supplemented. The goats in the two treatment groups were supplemented either 100 g of mixed feed containing corn, wheat bran, CaCO3 and trace of CuS04 (CA:P = 1.5:1) or 100 g of soybean meal per goat per day for six months of the first annual dry grass season. The results show that tooth wear decreased with increased protein supplementation. The heights of the first pairs of incisors, developed during the feed supplementation period and measured after a succeeding six month green gras season, were: 6.2 ± 0.8 mm (control), 8.9 ± 2.0 mm (mixed feed) and 11.1 ± 1.3 mm (soybean), respectively. This paper discusses the relationship between nutrition and tooth wear.
We have modified and improved a colorimetric method for determining total serum lipids [Amer. J. Clin. Pathol. 53, 89 (1970)]. The improved procedure requires only 20 µl of serum, and the entire determination is done in one tube, thus eliminating the tedious pipetting of a concentrated sulfuric acid-serum digest. The phospho-vanillin reagent has been modified so that the linearity of the method now extends to 1250 mg/dl. Concentrations up to 1240 mg/dl or of bilirubin up to 20 mg/dl in the serum do not interfere. The relative standard deviation for the method (day-to-day) is 4.9%.
Feeding a protein-deficient diet to male mice treated for 30 days with NaF (5, 10, 20 mg/kg body weight) caused a significant decrease in protein levels in testis, cauda epididymis, and vas deferens. The activity of testicular SDH and 3β- and 17β-HDS as well as ATPase in cauda epididymis and vas deferens also decreased as compared to controls fed a normal protein diet. The decrease was more significant in mice treated with 10 and 20 mg NaF/kg than with 5 mg/kg. By contrast, levels of cholesterol in testis and glycogen in the vas deferens were significantly enhanced as compared to controls. A protein-supplemented diet fed along with NaF in the same three doses did not cause any change in these parameters, which remained the same as the controls. These results clearly indicate that protein supplementation is beneficial to overcome the toxic effects of fluoride on testicular steroidogenesis, protein, carbohydrate, and energy and oxidation metabolisms in the reproductive organs of male mice. Protein deficiency, on the other hand, aggravates fluoride toxicity. A protein-supplemented diet might therefore substantially mitigate certain fluoride-induced health hazards in humans living in endemic areas.
Oral administration of sodium fluoride (NaF, 6 and 12 mg/kg body weight/ day) to Swiss male albino mice for 30 days caused significant, dose-dependent reduction in DNA, RNA, and protein contents in cerebral hemisphere, cerebellum, and medulla oblongata of the brain. After 30 days of NaF treatment, followed by withdrawal of treatment for 30 days, partial but significant amelioration occurred. Administration of 2% black tea extract alone for 30 days did not cause any significant effect. However, concurrent administrations of NaF and black tea extract for 30 days cause significant amelioration in all parameters studied.
1. Oxygen is a toxic gas - an introductionto oxygen toxicity and reactive species 2. The chemistry of free radicals and related 'reactive species' 3. Antioxidant defences Endogenous and Diet Derived 4. Cellular responses to oxidative stress: adaptation, damage, repair, senescence and death 5. Measurement of reactive species 6. Reactive species can pose special problems needing special solutions. Some examples. 7. Reactive species can be useful some more examples 8. Reactive species can be poisonous: their role in toxicology 9. Reactive species and disease: fact, fiction or filibuster? 10. Ageing, nutrition, disease, and therapy: A role for antioxidants?
Polyphenols are among a wide variety of active photochemicals present in the human diet. Basic researches and epidemiological studies have shown the inverse association between risk of cancer, CVDs, diabetes, several age related chronic diseases and intake of diet rich in polyphenols. Recent researches have opened the possibility of dietary polyphenols to be considered as phytomedicine. Most of the studies on the bioactivity of polyphenols have been conducted on animal models and in in vitro systems, direct studies on humans are few and results inconclusive. The bioavailability and biotransformation of polyphenols in humans needs to be studied. The present review provides an update about dietary polyphenols covering their nature, occurrence, bioavailability, and possible health benefits in relation to human diseases.
Fluoride is an environmental and industrial pollutant. It has already been reported that the accumulation of fluoride can
alter the activities of some enzymes involved in the free-radical metabolism and also decrease the activities of some enzymes
involved in the antioxidant defense system. In the present study, we have investigated the antioxidative properties of aqueous
extract of the bark of Terminalia arjuna (TA) on sodium fluoride (NaF) induced oxidative damages in the livers and kidneys of Swiss albino mice. The mice were treated
with 600ppm NaF for one week in drinking water and the activities of antioxidant enzymes, like superoxide dismutase (SOD),
catalase (CAT), and glutathione-S-transferase (GST), and the levels of non-protein thiol, reduced glutathione (GSH), along
with lipid peroxidation in the liver and kidney, were determined. Fluoride administration significantly altered the levels
of all of the factors compared to that of normal mice. Dose- and time-dependent studies suggest that the aqueous extract of
the bark of TA showed optimum protective activity against NaF-induced oxidative damages at a dose of 40mg/kg body weight
for 10days. Oral administration of the extract for the specified dose and time followed by NaF treatment (600ppm) normalized
the levels of the hepatic and renal antioxidant enzymes, GSH, and lipid peroxidation significantly to almost normal levels.
The effects of a known antioxidant, vitamin E, and a non-relevant agent, bovine serum albumin (BSA), have also been included
in the study. In addition, TA extract has been found to possess radical scavenging activity. Combining all of the data, the
results suggest that TA might possess a protective role against NaF-induced hepatic and renal oxidative damages, probably
via its antioxidant properties.
The present study was conducted to investigate the role of arjunolic acid (AA) against sodium fluoride (NaF)-induced cytotoxicity and necrotic cell death in murine hepatocytes. Dose-dependent studies suggest that incubation of hepatocytes with NaF (100mM) for 1h significantly decreased the cell viability as well as intracellular antioxidant power. Besides, NaF administration increased the activities of the membrane leakage enzymes and accumulation of intracellular reactive oxygen species; decreased the activities of the antioxidant enzymes, the glutathione (GSH) and total thiol contents; and elevated the level of oxidised glutathione (GSSG), lipid peroxidation end products as well as protein carbonyl content. In addition to the oxidative impairments, fluoride exposure caused hepatic cell death mainly via the necrotic pathway as supported by the flowcytometric and DNA fragmentation analyses. Incubation with AA (100 microg/ml) both prior to and in combination with NaF almost normalized the altered activities of antioxidant indexes. AA treatment enhanced the cellular antioxidant capability and protected hepatocytes against NaF-induced cytotoxicity and necrotic death. The cytoprotective activity of AA was found to be comparable to that of a known antioxidant, vitamin C. Combining, data suggest that AA plays a protective role against NaF-induced cellular damage and prevents hepatocytes from necrotic death.
The reaction of lipid peroxides in animal tissues with thiobarbituric acid was dependent on pH of the reaction mixture as was the case for linoleic acid hydroperoxide. The optimum pH was found to be 3.5. Taking this fact into consideration, a standard procedure for the assay of lipid peroxide level in animal tissues by their reaction with thiobarbituric acid was developed as follows. Ten percent ( tissue homogenate was mixed with sodium dodecyl sulfate, acetate buffer (pH 3.5), and aqueous solution of thiobarbituric acid. After heating at 95°C for 60 min, the red pigment produced was extracted with n-butanol-pyridine mixture and estimated by the absorbance at 532nm. As an external standard, tetramethoxy-propane was used, and lipid peroxide level was expressed in terms of nmol malondialdehyde. Using this method, the liped peroxide level in the liver of rats suffering from carbon tetrachloride intoxication was investigated. The results were in good agreement with previously reported data obtained by measuring diene content.
It has been suggested that calcium interferes with absorption of fluoride and that it diminishes the effect this ion has of increasing the bone mass when taken orally. Normal volunteers were given a combination of fluoride and calcium carbonate or fluoride alone, and serum levels of fluoride were measured to determine the effect, if any, of the concomitant administration of calcium on absorption of fluoride. The results indicate that 1.3 g of calcium, as the carbonate, decreases the integrated blood fluoride values by 22%.
A factorial experiment was conducted with weanling rats fed a purified diet to determine the influence of dietary protein type (casein or lactalbumin) and level (120 or 360 g/kg) on fluoride bioavailability (2 or 10 mg/kg as NaF). Although total food intake during the 4-wk study was similar for all eight treatment groups, rats fed the high protein--containing diets gained significantly (P less than 0.001) more weight than did rats fed the low protein--containing diets. Rats fed high protein diets absorbed significantly (P less than 0.001) more fluoride than rats fed low protein diets at either fluoride level regardless of protein type. The fraction of absorbed fluoride that was actually retained, however, was significantly (P less than 0.001) reduced by high protein at either fluoride level regardless of protein type. This depressive effect of high dietary protein on retained fluoride was reflected in femur fluoride concentration. Our results suggest that food fluoride, such as that originating from preparation of foods with fluoridated water, will be less bioavailable for an individual ingesting a high protein diet than for an individual fed a low protein diet.
Thanks to the pioneering work of Elizabeth and James Miller1 it is now well established that the cytotoxic and carcinogenic effects of a wide variety of chemicals are mediated by reactive products formed during their biotransformation in the organism. It is equally clear that there exist a number of protective systems which can trap, or inactivate, toxic metabolites and thereby prevent their accumulation within the tissues and subsequent toxic effects. Although phase I reactions, in particular those mediated by the cytochrome P-450-linked monooxygenase system, are most often responsible for the production of toxic metabolites, there are now many examples of metabolic activation via phase II reactions, despite the fact that the latter normally serve a protective function. Hence, it is obvious that the formation of toxic metabolites cannot be attributed to any single enzyme or enzyme system, and that the balance between metabolic activation and inactivation is absolutely critical in deciding whether exposure to a potentially toxic compound will result in toxicity, or not.
A method for estimating the cholesterol content of the serum low-density lipoprotein fraction (Sf- 0.20)is presented. The method involves measure- ments of fasting plasma total cholesterol, tri- glyceride, and high-density lipoprotein cholesterol concentrations, none of which requires the use of the preparative ultracentrifuge. Cornparison of this suggested procedure with the more direct procedure, in which the ultracentrifuge is used, yielded correlation coefficients of .94 to .99, de- pending on the patient population compared. Additional Keyph rases hyperlipoproteinemia classifi- cation #{149} determination of plasma total cholesterol, tri- glyceride, high-density lipoprotein cholesterol #{149} beta lipo proteins
This laboratory has previously postulated that bromobenzene-induced hepatic necrosis results from the formation of a reactive metabolite that arylates vital cellular macromolecules. Accordingly, the severity of liver necrosis has been compared with the formation of metabolites of bromobenzene and with covalent binding of metabolites in vivo and in vitro after various pretreatment regimens that alter hepatotoxicity. These data provide direct kinetic evidence that 3,4-bromobenzene oxide is the reactive hepatotoxic metabolite. The studies also demonstrate that the hepatotoxic metabolite is preferentially conjugated (detoxified) with glutathione, thereby depleting glutathione from the liver. Liver necrosis and arylation of cellular macromolecules occur only when glutathione is no longer available. Thus, a dose threshold exists for bromobenzene-induced hepatic necrosis.
Experimental fluorosis was induced in monkeys maintained on different levels of dietary protein, calcium, and vitamin C. Elevation of serum alkaline phosphatase and formation of abnormal bone deposits were observed in animals receiving fluoride on low-calcium and low-vitamin-C diets. Adequate calcium and vitamin C in the diet were found to mitigate the toxic effects of fluoride. Fluoride on low-protein diet appeared to accelerate the development of rarefaction of bones. Administration of fluoride did not appear to alter the major bone constituents (ash, calcium, phosphorus, collagen-protein and total protein). Higher amounts of fluoride were found to be retained in the bones of animals maintained on low-calcium diets.
Singlet oxygen, generated by photoexcitation or by chemiexcitation, selectively reacts with the deoxyguanosine moiety in DNA (kq + kr about 5 x 10(6) M-1s-1). The oxidation products include 8-oxo-7,8-dihydroeoxyguanosine (8-oxodG; also called 8-hydroxydeoxyguanosine) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua). Singlet oxygen also causes strand breaks in DNA, studied in plasmids and bacteriophages. The biological consequences include a loss of transforming activity as well as mutagenicity and genotoxicity. Employing shuttle vectors, it was shown that double-stranded vectors carrying singlet-oxygen-induced lesions seem to be processed in mammalian cells by DNA repair mechanisms efficient in preserving the biological activity of the plasmid but highly mutagenic in mammalian cells. Biological protection against singlet oxygen is afforded by quenchers, notably carotenoids (kq = 10(9) - 10(10) M-1s-1) and tocopherols. Whether this activity explains the protective effect of carotenoids on neoplastic transformation is still unknown.
Oral administration of sodium fluoride (NaF; 40 mg/kg body weight) daily from day 6 of gestation to day 21 of lactation caused, compared with the distilled water control (group 2), significant reductions in body weight and feed consumption as well as concentration of glucose and protein in the serum of P- and F(1)-generation rats; however, sodium and potassium concentrations in the serum were significantly higher than those of the vehicle control (group 2). Administration of either vitamins C (50 mg/kg body weight/day), D (2 ng/0.2 ml olive oil/animal/day) or a combination of vitamins C+D+E along with NaF caused significant amelioration in body weight and feed consumption, as well as glucose, protein, sodium and potassium concentrations in the serum of P- and F(1)-generation rats compared with the NaF-only treated group. Withdrawal of NaF treatment during lactation caused significant amelioration in feed consumption (days 15-21 only), sodium, potassium, glucose and protein concentrations in the serum of both P- and F(1)-generation rats. Co- treatment with vitamin E (2 mg/0.2 ml olive oil/animal/day) caused significant amelioration in body weight (days 15 and 20 of gestation only), sodium, potassium, glucose (only in P-generation females) and protein (only in P-generation female) concentrations in the serum of rats than in NaF-treated rats alone. It is concluded that co-treatment with vitamins C, D and C+D+E were found more effective in ameliorating NaF-induced effects than vitamin E and withdrawal of NaF treatment during lactation.
The aim of this work was to examine the effect of fluoride ions on antioxidative enzyme activity in the pancreas of rats exposed during 4 months to NaF in drinking water. The study was carried out in 30 four-week-old male Wistar FL rats, that were randomly assigned to three equal groups and given distilled water ad libitum for three weeks. Subsequently, two examined groups of animals were exposed to NaF in drinking water: group 1 (10 rats) at 50 mg F(-)/L (2.63 mmol/L), group 2 (10 rats) at 100 mg F(-)/L (5.26 mmol/L). The control group (10 rats) received distilled water. After 4 months the animals were anesthetized with ether prior to collection of pancreas and cardiac blood. Serum concentrations of glucose and fluoride, as well as activities of the cytoplasmic (CuZn-SOD) and the mitochondrial (Mn-SOD) superoxide dismutase, glutathione peroxidase (GSH-Px) and concentrations of malondialdehyde (MDA) in the homogenized pancreas were measured. The activity of CuZn-SOD was reduced by 50% and a tendency to lower activities of Mn-SOD was observed. No changes were noted in the activity of GSH-Px or concentrations of MDA. We conclude that: 1) the fluoride caused hyperglycemia in rats in this study is not accompanied by an activation of the free radical production in the pancreas; 2) the hyperglycemia in the exposed rats cannot be attributed to pancreatic damage caused by fluoride ions (the cause in this case appears to be extrapancreatic); 3) the inhibition of pancreatic CuZn-SOD is probably due to the direct action of fluoride on the enzyme.