Arsenic and fluoride: two major ground water pollutants.

Increasing human activities have modified the global cycle of heavy metals, non metals and metalloids. Both arsenic and fluoride are ubiquitous in the environment. Thousands of people are suffering from the toxic effects of arsenicals and fluorides in many countries all over the world. These two elements are recognized worldwide as the most serious inorganic contaminants in drinking water. Many studies have reported as regards to simple fluorosis and arsenicosis, but the knowledge of the joint action of these two elements is lacking and the results derived from previous studies were inconclusive. Contradictory results were reported in experimental studies in which different joint actions such as independent, synergistic and antagonistic effects were observed. This indicates that interaction mechanism of these two elements is considerable complicated and requires extensive studies. When two different types of toxicants are simultaneously going inside a human body they may function independently or can act as synergistic or antagonistic to one another. Thus there is an urge to resolve the question that how arsenic and fluoride act in condition of concomitant exposure. Although there have been reports in literature of individual toxicity of arsenic and fluoride however, there is very little known about the effects following the combined exposure to these toxicants. This review focused on recent developments in the research on the condition of individual exposure to arsenic and fluoride along with the recent updates of their combined exposure to better understand the joint action of these two toxicants.

Fluoride-induced changes in haem biosynthesis pathway, neurological variables and tissue histopathology of rats.

This study intended to determine the effects of various concentrations of fluoride (1, 10, 50 and 100 ppm) in drinking water for a period of 12 weeks on changes in haem biosynthesis pathway, oxidative stress and neurological variables supported by histopathological observations and fluoride in rats. The data indicates significant alterations in the parameters related to haeme synthesis pathway like inhibition of blood delta-aminolevulinic acid dehydratase, delta-aminolevulinic acid synthetase, oxidative stress like depletion of glutathione (GSH) and increase in oxidized glutathione (GSSG) and thiobarbituric acid reactive substances. These changes were accompanied by depletion in GSH:GSSG ratio, whole brain biogenic amine levels and a dose-dependent increase in fluoride concentration. Interestingly and most significantly, these changes were more pronounced at lower concentrations of fluoride compared with higher fluoride dose. Biochemical changes were supported by the histological observations, which also revealed that at high concentrations of fluoride, toxic effects and damages to organs were more pronounced. These changes support our earlier findings regarding the role of decreased ionic mobility of fluoride ion at higher concentrations, leading to less pronounced toxicity.

Effects of fluoride on the tissue oxidative stress and apoptosis in rats: biochemical assays supported by IR spectroscopy data.

The mechanism underlying the toxicity of fluoride still remains unknown. To investigate the effects of different doses of fluoride on blood and tissue oxidative stress and apoptosis, we exposed male rats to three doses of fluoride (10, 50 and 100ppm in drinking water) for a period of 10 weeks. The results suggested that exposure to 10ppm fluoride significantly increased the level of reactive oxygen species (ROS) in blood accompanied by a decrease in glutathione (GSH) level. No evidences of oxidative stress in soft tissues were seen. Fluoride (10ppm) also decreased GSH/GSSG ratio significantly. Contrary to expectation, 50 and 100ppm fluoride exposure did not produce a more pronounced toxicity in the soft tissues. However, we observed a significantly elevated concentration of ROS and depleted GSH level in blood. Exposure to fluoride did not produce any sign of apoptosis. To support our above mentioned biochemical observations and to suggest possible mechanism of action of fluoride, IR spectra of brain tissues were recorded. The results of these spectra indicated significant shift in the characteristic peak of -OH group in animals exposed to 10ppm fluoride however at higher doses, the shift was minimal. It can thus be concluded that fluoride-induced toxicity is mediated through oxidative stress particularly at a comparatively lower level of exposure however at the higher doses the mode of action still unclear and needs further investigation.

Combined administration of taurine and monoisoamyl DMSA protects arsenic induced oxidative injury in rats.

Arsenic is a naturally occurring element that is ubiquitously present in the environment. High concentration of naturally occurring arsenic in drinking water is a major health problem in different parts of the world. Despite arsenic being a health hazard and a well documented carcinogen, no safe, effective and specific preventive or therapeutic measures are available. Among various recent strategies adopted, administration of an antioxidant has been reported to be the most effective. The present study was designed to evaluate the therapeutic efficacy of monoisoamyl dimercaptosuccinic acid (MiADMSA), administered either individually or in combination with taurine post chronic arsenic exposure in rats. Arsenic exposed male rats (25 ppm, sodium arsenite in drinking water for 24 weeks) were treated with taurine (100 mg/kg, i.p., once daily), monoisoamyl dimercaptosuccinic acid (MiADMSA) (50 mg/kg, oral, once daily) either individually or in combination for 5 consecutive days. Biochemical variables indicative of oxidative stress along-with arsenic concentration in blood, liver and kidney were measured. Arsenic exposure significantly reduced blood delta-aminolevulinic acid dehydratase (ALAD) activity, a key enzyme involved in the heme biosynthesis and enhanced zinc protoporphyrin (ZPP) level. Clinical hematological variables like white blood cells (WBC), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC) showed significant decrease with a significant elevation in platelet (PLT) count. These changes were accompanied by significant decrease in superoxide dismutase (SOD) activity and increased catalase activity. Arsenic exposure caused a significant decrease in hepatic and renal glutathione (GSH) level and an increase in oxidized glutathione (GSSG). These biochemical changes were correlated with an increased uptake of arsenic in blood, liver and kidney. Administration of taurine significantly reduced hepatic oxidative stress however co-administration of a higher dose of taurine (100 mg/kg) and MiADMSA provided more pronounced effects in improving the antioxidant status of liver and kidney and reducing body arsenic burden compared to the individual treatment of MiADMSA or taurine. The results suggest that in order to achieve better effects of chelation therapy, co-administration of taurine with MiADMSA might be preferred.