Paraoxonase 1 activity in subchronic low-level inorganic arsenic exposure through drinking water.

Epidemiological evidences indicate close association between inorganic arsenic exposure via drinking water and cardiovascular diseases. While the exact mechanism of this arsenic-mediated increase in cardiovascular risk factors remains enigmatic, epidemiological studies indicate a role for paraoxonase 1 (PON1) in cardiovascular diseases. To investigate the association between inorganic arsenic exposure and cardiovascular diseases, rats were exposed to sodium arsenite (trivalent; 50, 100, and 150 ppm As) and sodium arsenate (pentavalent; 100, 150, and 200 ppm As) in their drinking water for 12 weeks. PON1 activity towards paraoxon (PONase) and phenylacetate (AREase) in plasma, lipoproteins, hepatic, and brain microsomal fractions were determined. Inhibition of PONase and AREase in plasma and HDL characterized the effects of the two arsenicals. While the trivalent arsenite inhibited PONase by 33% (plasma) and 46% (HDL), respectively, the pentavalent arsenate inhibited the enzyme by 41 and 34%, respectively. AREase activity was inhibited by 52 and 48% by arsenite, whereas the inhibition amounted to 72 and 67%, respectively by arsenate. The pattern of inhibition in plasma and HDL indicates that arsenite induced a dose-dependent inhibition of PONase whereas arsenate induced a dose-dependent inhibition of AREase. In the VLDL + LDL, arsenate inhibited PONase and AREase while arsenite inhibited PONase. In the hepatic and brain microsomal fractions, only the PONase enzyme was inhibited by the two arsenicals. The inhibition was more pronounced in the hepatic microsomes where a 70% inhibition was observed at the highest dose of pentavalent arsenic. Microsomal cholesterol was increased by the two arsenicals resulting in increased cholesterol/phospholipid ratios. Our findings indicate that decreased PON1 activity observed in arsenic exposure may be an incipient biochemical event in the cardiovascular effects of arsenic. Modulation of PON1 activity by arsenic may also be mediated through changes in membrane fluidity brought about by changes in the concentration of cholesterol in the microsomes.

Arsenic-induced dyslipidemia in male albino rats: comparison between trivalent and pentavalent inorganic arsenic in drinking water.

BACKGROUND: Recent epidemiological evidences indicate close association between inorganic arsenic exposure via drinking water and cardiovascular diseases. However, the exact mechanism of this arsenic-mediated increase in cardiovascular risk factors remains enigmatic. METHODS: In order to investigate the effects of inorganic arsenic exposure on lipid metabolism, male albino rats were exposed to 50, 100 and 150 ppm arsenic as sodium arsenite and 100, 150 and 200 ppm arsenic as sodium arsenate respectively in their drinking water for 12 weeks. RESULTS: Dyslipidemia induced by the two arsenicals exhibited different patterns. Hypocholesterolemia characterised the effect of arsenite at all the doses, but arsenate induced hypercholesterolemia at the 150 ppm As dose. Hypertriglyceridemia was the hallmark of arsenate effect whereas plasma free fatty acids (FFAs) was increased by the two arsenicals. Reverse cholesterol transport was inhibited by the two arsenicals as evidenced by decreased HDL cholesterol concentrations whereas hepatic cholesterol was increased by arsenite (100 ppm As), but decreased by arsenite (150 ppm As) and arsenate (100 ppm As) respectively. Brain cholesterol and triglyceride were decreased by the two arsenicals; arsenate decreased the renal content of cholesterol, but increased renal content of triglyceride. Arsenite, on the other hand, increased the renal contents of the two lipids. The two arsenicals induced phospholipidosis in the spleen. Arsenite (150 ppm As) and arsenate (100 ppm As) inhibited hepatic HMG CoA reductase. At other doses of the two arsenicals, hepatic activity of the enzyme was up-regulated. The two arsenicals however up-regulated the activity of the brain enzyme. We observed positive associations between tissue arsenic levels and plasma FFA and negative associations between tissue arsenic levels and HDL cholesterol. CONCLUSION: Our findings indicate that even though sub-chronic exposure to arsenite and arsenate through drinking water produced different patterns of dyslipidemia, our study identified two common denominators of dyslipidemia namely: inhibition of reverse cholesterol transport and increase in plasma FFA. These two denominators (in addition to other individual perturbations of lipid metabolism induced by each arsenical), suggest that in contrast to strengthening a dose-dependent effect phenomenon, the two forms of inorganic arsenic induced lipotoxic and non-lipotoxic dyslipidemia at "low" or "medium" doses and these might be responsible for the cardiovascular and other disease endpoints of inorganic arsenic exposure through drinking water.

Effect of highways and local activities on the quality of underground water in Ogun State, Nigeria: a case study of three districts in Ogun State, Nigeria.

The effect of highways and local activities on the quality of groundwater in Ogun State, Nigeria was investigated. This was done by collecting groundwater samples from three different districts in the state, located in Southwestern Nigeria. The water samples collected at 5 m from the highway and control samples collected at 3 km from the highway were analyzed for the following physicochemical parameters: pH, conductivity, chemical oxygen demand, alkalinity, total hardness, total solid, suspended solid, dissolved solid, chloride, sulfate, phosphate, nitrate, phenol, and the metals-lead, zinc, iron, aluminum, sodium, and potassium. The levels of chromium, copper, and cadmium in the samples were below the detectable limit. The levels of the parameters show that there are significant differences between those in the samples and the controls (F test) except for phosphate and phenol. Also, anthropogenic sources (local activities) elevate the levels of different specific parameters, which are related to these activities. Good correlation was observed between traffic density and lead levels as well as between conductivity and dissolved solids. Comparisons with the World Health Organization guidelines indicate that most of the water samples are not suitable for human consumption.