Potential Health Risks Associated with the Heavy Metal Content in Commonly Consumed Food from Prakasam District of Andhra Pradesh, India.

The present study investigated the heavy metal (HM) accumulation in some food items and associated potential human health risk in the Prakasam district. Food samples were collected from 9 villages of different mandals mainly comprising of rice, wheat, green gram, red gram, black gram, potato, and amaranthus. The HMs chromium (Cr), arsenic (As), lead (Pb), cadmium (Cd), and mercury (Hg) were analyzed by Inductively Coupled Plasma Mass Spectroscopy (ICPMS). The results showed that the HM concentrations in vegetables were higher than the cereals and pulses. The decreasing order of HM concentrations were observed as Cr > As > Pb > Cd > Hg, Cr > Pb > As = Cd > Hg and Cr > Pb > Cd > As > Hg in cereals, pulses, and vegetables, respectively. The dietary intake of cereals and vegetables contributed more exposure to HMs. The hazard index (HI) in case of cereals (3.648) and vegetables (1.003) exceeded 1 indicating the non-carcinogenic risk when these food items are consumed by adults. The HI in case of cereals (7.106) and vegetables (1.747) exceeded 1 indicating the health risks when these food items were consumed by children. The HI for cereals and vegetables in case of children is almost double to the HI of adults. The lifetime cancer risk was observed for Cr via consumption of rice and amaranthus, both in adults and children. In conclusion, health risk due to consumption of cereals and vegetables revealed both non-carcinogenic and carcinogenic risk for adults and children. The findings of the present study can be used for the development of potential strategies for risk control and management.

Arsenic-induced uterine apoptotic damage is protected by ethyl acetate fraction of Camellia sinensis (green tea) via Bcl-2-BAX through NF-κB regulations in Wistar rats.

The non-invasive treatment strategy is indispensable to overcome the side effects of conventional treatment with chelating agents against arsenic. Presence of catechins and flavonoids in Camellia sinensis have potential antioxidant properties and other beneficial effects. The aim of the study was to explore the curative potential role of Camellia sinensis against uterine damages produced by sodium arsenite in mature albino rats. A dose of 10 mg of Camellia sinensis ethyl acetate (CS-EA) fraction/100 gm body weight was provided to the sodium arsenite-treated rats (10 mg/Kg body weight). LC-MS analysis was used for the detection of active component in CS-EA fraction. Enzymatic antioxidants analysis carried out by reproducible native gel technique. Hormones and some pro and anti-inflammatory markers were detected by ELISA, PCR, and western blot techniques respectively. Immunostaining was performed for the detection of estradiol receptor alpha. LC-MS analysis of CS-EA fraction ensured the presence of active tea polyphenol and tea catechin of which highest peak of epigallocatechin-3 gallate (EGCG) was obtained in this study. Significant elevations of lipid peroxidation end products followed by the diminution of antioxidant enzymes activities were noted in arsenicated rats which were capably retrieved by the treatment of CS-EA fraction. Post-treatment with CS-EA fraction meaningfully improved gonadotrophins and estradiol signalling in association with a highly expressing estradiol receptor-α (ERα) in the ovary and uterus followed by the maintenance of normal utero-ovarian histoarchitecture in arsenic fed rats. CS-EA fractioned treated group overturned the sodium arsenite driven higher expression of pro-inflammatory cytokines and proapoptotic markers along with a low level of anti apoptotic Bcl-2 expression and comparatively lower NF-κB signalling in the uterus via regulating IKK ß kinase mostly by EGCG of CS-EA fraction. However, ethyl acetate fraction of Camellia sinensis played a critical role in minimizing arsenic-mediated uterine hypo-function.

Supplementation of Calcium and Fluoride-Free Water Mitigates Skeletal Fluorosis in Fluoride-Intoxicated Rats.

Fluorosis is a public health concern in 25 countries around the globe. The present study is about the mitigation of fluoride (F) toxicity by giving F-free water (FFW) and calcium (Ca). A study was conducted by taking 76 Wistar rats in two phases, phase I (6 months), where rats were randomly divided into four groups: normal-Ca diet (NCD) 0.5%; low-Ca diet (LCD) 0.25%; NCD + 100 ppm F and LCD + 100 ppm F in groups 1, 2, 3 and 4, respectively. F and Ca were given through water and diet respectively. Phase II is the reversal of fluorosis for 3 months, where LCD group 2 was treated with NCD. Groups 3 and 4 were divided into two subgroups each: 3X and 3Y, and 4X and 4Y, respectively. Groups 3X and 4X received FFW with NCD. Group 3Y continued as phase I and 4Y NCD and F. The biochemical expression, gene expression, biomechanical properties and DXA were studied by standard methods. The results revealed that in phase I, bone turnover was significantly increased whereas bone mineral content and biomechanical properties of group 4 were significantly decreased (p ≤ 0.05) as compared with that of all other groups. Trabecular separation and total porosity increased in groups 2 and 4. Expression of osteocalcin, osteonectin and osteopontin genes was significantly downregulated in group 4. Bone turnover in group 4X was normalised. Expressions of osteocalcin, osteonectin and osteopontin were upregulated after providing NCD and FFW. In conclusion, low calcium aggravates skeletal fluorosis which could be mitigated on supplementation of Ca and FFW.

Neurolathyrism in goat (Capra hircus) kid: Model development.

The present study was undertaken to develop an animal model to study neurolathyrism. For this purpose 24 goat (Capra hircus) kids (new born, 15 days old) were divided into four groups. Group I Control, Group II Low toxin (0.17 g% ß-ODAP containing grass pea), Group III high toxin (0.96 g% ß-ODAP containing grass pea) and Group IV high toxin (0.96 g% ß-ODAP containing grass pea flour (powder) fortified with 5 mg% pure ß-ODAP). The experiment was continued for 3 months. Clinical examination was carried out weekly. Muscle conduction velocity (MCV), nerve conduction velocity (NCV), blood and urinary ß-ODAP, nitrite in blood and cerebrospinal fluid (CSF) examination were performed by standard methods. Clinical examination showed neurolathyrism symptoms in three kids. The abnormal MCV and NCV were observed in all the experimental animals. Blood nitrite, blood and urine ß-ODAP levels were significantly increased in experimental groups. Three kids were affected with neurolathyrism due to consumption of grass pea irrespective of its ß-ODAP content and kid may serve as a neurolathyrism model.

Current scenario of consumption of Lathyrus sativus and lathyrism in three districts of Chhattisgarh State, India.

Lathyrism is a disease caused by excessive consumption of grass pea, Lathyrus sativus especially under conditions of severe drought. Grass pea contains 3-N-oxalyl-L-2, 3-diaminopropanoic acid (ß-ODAP) a putative neurotoxin which acts through excitatory mechanism causing Neurolathyrism. Due to awareness of the disease, availability of food and levels of consumption of L. sativus there is reduction in lathyrism cases where higher consumption of L. sativus is reported in India. The present study was undertaken with the objective to assess the current scenario of consumption of L. sativus, incidence of cases of lathyrism, ß-ODAP, protein and amino acids content in L. sativus pulse collected from three districts (Bilaspur, Durg and Raipur) of Chattisgarh state. For this purpose, a total of 17,755 (13,129 rural and 4626 urban) individuals from 151 villages and 60 wards from urban area were covered for clinical examination. Out of total 5769 households (HHs) covered during the survey, 1602 HHs were cultivators, 1791 HHs non-cultivators and 2376 agricultural and other labourers. A one day 24-hour re-call diet survey was carried out in 5758 HHs (4549 rural and 1209 urban). A total of 360 split grass pea (SGP) samples were collected to estimate ß-ODAP, protein and amino acids content. Results of the study revealed that an average consumption of SGP was 20.9 gm/CU/day in Bilaspur and no consumption was reported among urban population of Raipur. Only nine old cases of lathyrism were found during the study. The mean ß-ODAP content in SGP was 0.63 ±â€¯0.14, 0.65 ±â€¯0.13 and 0.65 ±â€¯0.14 gm/100 gm, whereas the protein content was 27.0 ±â€¯2.39, 27.0 ±â€¯1.99 and 26.7 ±â€¯1.90 gm/100 gm in samples collected from Bilaspur, Durg and Raipur districts respectively. Arginine content was high in SGP and sulphur containing amino acids (cysteine and methionine) were less than other amino acids. In conclusion, the consumption of SGP was lower in these three districts with lower ß-ODAP content than earlier reports, thus the lower prevalence of lathyrism in the districts surveyed.

Fluoride Alters Serum Elemental (Calcium, Magnesium, Copper, and Zinc) Homeostasis Along with Erythrocyte Carbonic Anhydrase Activity in Fluorosis Endemic Villages and Restores on Supply of Safe Drinking Water in School-Going Children of Nalgonda District, India.

The present study aimed to determine the serum trace elements (copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg)) along with erythrocyte carbonic anhydrase (CA) activity and effect of intervention with safe drinking water for 5 years in the school children of fluorosis endemic area. For this purpose, three categories of villages were selected based on drinking water fluoride (F): Category I (control, F = 1.68 mg/L), category II (affected F = 3.77 mg/L), and category III (intervention village) where initial drinking water F was 4.51 mg/L, and since the last 5 years, they were drinking water containing < 1.0 mg/L F. The results revealed that urinary F was significantly (P < 0.05) higher in category II compared to categories I and III. A significant (P < 0.05) increase in serum Cu and Mg was observed in category II compared to category I. Serum Zn and Ca was significantly (P < 0.05) decreased in categories II and III compared to category I. The erythrocyte CA activity was decreased in the category II compared to category I. However, in the category III, erythrocyte CA activity was comparable to the control group. In conclusion, F exposure altered elemental homeostasis which has restored to some extent on intervention by safe drinking water for 5 years in school-going children.

Dose-dependent effect of fluoride on clinical and subclinical indices of fluorosis in school going children and its mitigation by supply of safe drinking water for 5 years: an Indian study.

Fluorosis is a public health problem in India; to know its prevalence and severity along with its mitigation measures is very important. The present study has been undertaken with the aim to assess the F dose-dependent clinical and subclinical symptoms of fluorosis and reversal of the disease by providing safe drinking water. For this purpose, a cross-sectional study was undertaken in 1934 schoolgoing children, Nalgonda district. Study villages were categorized into control (category I, F = 0.87 mg/L), affected (category II, F = 2.53 mg/L, and category III, F = 3.77 mg/L), and intervention categories (category IV, F = < 1.0 mg/L). School children were enrolled for dental grading by modified Dean Index criteria. Anthropometric measurements (height and weight) were used to assess nutritional status of the children. The biochemical parameters like serum T3, T4, TSH, PTH, ALP, 25-OH vitamin D, and 1,25-(OH)2 vitamin D were analyzed. The results showed a positive correlation between the drinking water and urinary fluoride (UF) in different categories. However, there was a significant decrease in the UF levels in the intervention category IV compared to affected group (category III). Fluoride altered the clinical (dental fluorosis and stunting) and subclinical indices (urine and blood) of fluorosis in a dose-dependent manner. In conclusion, the biochemical indices were altered in a dose-dependent manner and intervention with safe drinking water for 5 years in intervention group-mitigated clinical and subclinical symptoms of fluorosis.

Dental fluorosis, nutritional status, kidney damage, and thyroid function along with bone metabolic indicators in school-going children living in fluoride-affected hilly areas of Doda district, Jammu and Kashmir, India.

A case-control study was undertaken among the school children aged 8-15 years to know the presence and severity of dental fluorosis, nutrition and kidney status, and thyroid function along with bone metabolic indicators in Doda district situated at high altitude where drinking water was contaminated and heat stress. This study included 824 participants with an age of 8-15 years. The results of the study reviled that dental fluorosis was significantly higher in affected than control area children. Urinary fluoride was significantly higher (p < 0.05) in affected children as compared to the control area school children. Nutritional status of affected children was lower than control area children. The chronic kidney damage (CKD) was higher in affected than control school children. Thyroid function was affected more in affected than control area schools. Serum creatinine, total alkaline phosphatase, parathyroid hormone, 1, 25(OH)2 vitamin D, and osteocalcin were significantly higher in affected school children (p < 0.05) as compared to control school children, whereas there was no significant difference in triiodothyronine (T3), thyroxine (T4), and 25-OH vitamin D among the two groups. There was a significant decrease in thyroid-stimulating hormone (TSH) in the affected area school children compared to control. In conclusion, fluorotic area school children were more affected with dental fluorosis, kidney damage, along and some bone indicators as compared to control school children.

Grass pea consumption & present scenario of neurolathyrism in Maharashtra State of India.

BACKGROUND & OBJECTIVES: Neurolathyrism is a non progressive motor neuron disorder engendered by the prolonged over-consumption of Lathyrus sativus (grass pea) seeds which contain a neurotoxic amino acid, ß-N oxalyl- L-α, ß-diaminopropionic acid (ß-ODAP). It is characterized by spastic paraparesis in the hind limbs. The present study was conducted in 105 households (HHs) of Gondia district in Maharashtra, India, where grass pea is cultivated and consumed to assess the health implication of its consumption. METHODS: Across-sectional survey was carried out in 105 HHS in five villages and grass pea samples were collected for ß-ODAP estimation. Amino acid analysis was also done, neurolathyrism cases were identified by snowball sampling method and neurological examination was carried out. RESULTS: The study revealed that 61 per cent of population was consuming this pulse as a part of diet. ß-ODAP concentration in grass pea was high in Bora village (1254.5 ± 528.21 mg %) and less in Malgaon village (413.6±415.79 mg %). The nutritional status of the people was within the normal range (BMI 18± 3.40 kg/m2) in the surveyed households. Consumption of grass pea was observed to be less than 25 g. CONCLUSIONS: The cases of neurolathyrism declined in all the studied villages due to reduced ß-ODAP exposure through Lathyrus sativus consumption, however, the grass pea was cultivated and consumed in Gondia district of Maharashtra State.

Exploring antiurolithic effects of gokshuradi polyherbal ayurvedic formulation in ethylene-glycol-induced urolithic rats.

Gokshuradi Yog (GY) is a polyherbal ayurvedic formulation used traditionally for several decades in India for the treatment of urolithiasis. The aim of the present study was to determine the underlying mechanism of GY action in the management of calcium oxalate urolithiasis. The effect of Gokshuradi polyherbal aqueous extracts (GPAEs) was studied on various biochemical parameters involved in calcium oxalate formation by employing in vitro and in vivo methods. GPAE exhibited significant antioxidant activity against 1, 1-diphenyl-2-picrylhydrazyl free radical and inhibited lipid peroxidation in the in vitro experiments. The rat model of urolithiasis induced by 0.75% ethylene glycol (EG) and 1% ammonium chloride (AC) in water caused polyuria, weight loss, impairment of renal function, and oxidative stress and decreased antioxidant enzyme activities in untreated control groups. However, GPAE- (25, 50, and 100 mg/kg) treated groups caused diuresis accompanied by a saluretic effect and revealed significant increase in antioxidant enzyme activities along with decreased oxalate synthesizing biochemical parameters at higher doses. This study revealed the antiurolithic effect of GPAE mediated possibly through inhibiting biochemical parameters involved in calcium oxalate formation, along with its diuretic and antioxidant effects, hence supporting its use in the treatment of calcium oxalate urolithiasis.

Amelioration of chronic fluoride toxicity by calcium and fluoride-free water in rats.

The study was undertaken to explore the amelioration of chronic fluoride (F) toxicity (with low and normal Ca) in rats. The study was conducted in two phases. In phase I (6 months), seventy-six Wistar, weanling male rats were assigned to four treatment groups: normal-Ca (0·5 %) diet (NCD), Ca+F - ; low-Ca (0·25 %) diet (LCD), Ca - F - ; NCD +100 parts per million (ppm) F water, Ca+F+; LCD +100 ppm F water, Ca - F+. In phase II (reversal experiment, 3 months), LCD was replaced with the NCD. Treatment groups Ca+F+ and Ca - F+ were divided into two subgroups to compare the effect of continuation v. discontinuation along with Ca supplementation on reversal of chronic F toxicity. In phase I, significantly reduced food efficiency ratio (FER), body weight gain (BWG), faecal F excretion, serum Ca and increased bone F deposition were observed in the treatment group Ca - F+. Reduced serum 25-hydroxy-vitamin D3, increased 1,25-dihydroxy-vitamin D3 and up-regulation of Ca-sensing receptor, vitamin D receptor and S100 Ca-binding protein G (S100G) were observed in treatment groups Ca - F - and Ca - F+. In phase II (reversal phase), FER, BWG and serum Ca in treatment groups Ca - F+/Ca+F - and Ca - F+/Ca+F+ were still lower, as compared with other groups. However, other variables were comparable. Down-regulation of S100G was observed in F-fed groups (Ca+F+/Ca+F+ and Ca - F+/Ca+F+) in phase II. It is concluded that low Ca aggravates F toxicity, which can be ameliorated after providing adequate Ca and F-free water. However, chronic F toxicity can interfere with Ca absorption by down-regulating S100G expression irrespective of Ca nutrition.

Role of glutamate and nitric oxide in onset of motor neuron degeneration in neurolathyrism.

Neurolathyrism is associated with a complex pattern of alterations in the glutamatergic system of the cortical motor region of brain. It is a neurological disorder consorted with excessive consumption of Lathyrus sativus (Grass pea), comprising large amounts of the neurotoxin, ß-N-oxalyl-L-α,ß-diaminopropionic acid (ODAP). ODAP being a potent agonist of ionotropic glutamate receptors enhances their activity and also blocks the astrocytic glutamate/cystine transporters, abutting the neurons. This leads to the sustained increase in the concentration of Glutamate in the synapse which triggers excitotoxicity. L. sativus also contains high levels of arginine and homoarginine which are natural substrates of nitric oxide production, when NO levels increases, it forms peroxynitrite radicals which cause irreparable damage to mitochondria and cellular macromolecules leading to motor neuron degeneration. This review brings together all the molecular events reported so far, emphasizing on the possible role of glutamate and nitric oxide mediated cell death.

Mineral content of water and food in fluorotic villages and prevalence of dental fluorosis.

The fluoride (F), calcium (Ca), magnesium (Mg), zinc (Zn), copper (Cu), and phosphorus (P) content in potable water and food samples from endemic and nonendemic villages for fluorosis were analyzed. It was found that the F content in water was significantly higher (p<0.01) in endemic villages (4.20+/-1.6 ppm) than control villages (0.63+/-0.15 ppm), whereas the Ca, Cu, and Mg contents were found to be significantly lower (p<0.05) in endemic villages compared to control villages. However, there was no significant difference in Zn and P contents between the villages. Foods grown in endemic villages contained significantly higher (p<0.01) fluoride content as compared to control villages. There was no significant difference in Ca, Mg, P, and Zn contents in food grown in endemic and control villages. Copper content in cereals (p<0.05), pulses (p<0.01), and vegetables (p<0.01) in endemic villages was found significantly higher as compared to control villages. The overall prevalence of dental fluorosis in six endemic villages was 97.4% in boys and 96% in girls, which was significantly higher (p<0.01) than that of control villages, where it was 10.5% in boys and 8.3% in girls. The prevalence of dental fluorosis was positively correlated (r=0.125, p<0.01) to fluoride and negatively correlated to Ca and Cu content in drinking water in endemic villages.

Additional beneficial effect of tamarind ingestion over defluoridated water supply to adolescent boys in a fluorotic area.

OBJECTIVE: We evaluated the effect of tamarind (Tamarindus indicus) on ingestion and whether it provides additional beneficial effects on mobilization of fluoride from the bone after children are provided defluoridated water. METHODS: A randomized, diet control study was conducted in 30 subjects from a fluoride endemic area after significantly decreasing urinary fluoride excretion by supplying defluoridated water for 2 wk. Subjects were then assigned to one of two groups, with 15 in each group. One group was supplemented with tamarind (experimental group) for 3 wk and the other (control) group was given only defluoridated water for the same period. RESULTS: The mean changes in urinary components after tamarind ingestion (volume, pH, fluoride calcium, copper, and magnesium) in the control and experimental groups were compared. There was a significant increase (P < 0.01) in fluoride excretion and urinary pH and a significant decrease in urinary calcium (P < 0.01) and copper (P < 0.05) excretion in the experimental group as compared with the control group. There was no change in urinary volume between groups. CONCLUSIONS: Tamarind intake appears to have an additional beneficial effect on the mobilization of deposited fluoride from bone, by enhancing urinary excretion of fluoride.

Antioxidant defense system and lipid peroxidation in patients with skeletal fluorosis and in fluoride-intoxicated rabbits.

Fluorosis is a serious public health problem in many parts of the world where drinking water contains more than 1 ppm of fluoride. The main manifestations of skeletal fluorosis are crippling bone deformities, spinal compressions, and restricted movements of joints. Although fluorosis is irreversible, it could be prevented by appropriate and timely intervention through understanding the process at biochemical and molecular levels. As in the case of many chronic degenerative diseases, increased production of reactive oxygen species (ROS) and lipid peroxidation has been considered to play an important role, even in the pathogenesis of chronic fluoride toxicity. However, there is inconclusive proof for an altered oxidative stress and antioxidant balance in fluorosis, and the existing data are not only conflicting but also contradictory. In the present communication we have evaluated the antioxidant defense system (both enzymatic and nonenzymatic) and lipid peroxidation in both humans from an endemic fluorosis area (5 ppm fluoride in the drinking water) and in rabbits receiving water with 150 ppm of fluoride for six months. There was no significant difference in lipid peroxidation, glutathione, and vitamin C in the blood of human fluorotic patients and fluoride-intoxicated rabbits as compared to respective controls. Neither were there any changes in the activities of catalase, superoxide dismutase, glutathione peroxidase, or glutathione S-transferase in the blood due to fluoride intoxication (of rabbits) or fluorosis in humans. The results together do not subscribe to oxidative stress theory in fluorosis. Thus, in the absence of clear proof of oxidative damage and to counter toxic effects of fluoride through supplementation of antioxidants, extensive investigations are needed to conclusively prove the role of oxidative stress in skeletal fluorosis.