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.

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.

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.

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.

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.