Age and Smoking Related Changes in Metal Ion Levels in Human Lens: Implications for Cataract Formation.

Age-related cataract formation is the primary cause of blindness worldwide and although treatable by surgical removal of the lens the majority of sufferers have neither the finances nor access to the medical facilities required. Therefore, a better understanding of the pathogenesis of cataract may identify new therapeutic targets to prevent or slow its progression. Cataract incidence is strongly correlated with age and cigarette smoking, factors that are often associated with accumulation of metal ions in other tissues. Therefore this study evaluated the age-related changes in 14 metal ions in 32 post mortem human lenses without known cataract from donors of 11 to 82 years of age by inductively coupled plasma mass spectrometry; smoking-related changes in 10 smokers verses 14 non-smokers were also analysed. A significant age-related increase in selenium and decrease in copper ions was observed for the first time in the lens tissue, where cadmium ion levels were also increased as has been seen previously. Aluminium and vanadium ions were found to be increased in smokers compared to non-smokers (an analysis that has only been carried out before in lenses with cataract). These changes in metal ions, i.e. that occur as a consequence of normal ageing and of smoking, could contribute to cataract formation via induction of oxidative stress pathways, modulation of extracellular matrix structure/function and cellular toxicity. Thus, this study has identified novel changes in metal ions in human lens that could potentially drive the pathology of cataract formation.

Effect of fasting on the pattern of urinary arsenic excretion.

Millions of people in some of the poorest regions of the world are exposed to high levels of arsenic through drinking contaminated water. It has been reported that development of cancer caused by arsenic exposure in such populations is dependent on dietary and nutritional factors which can modulate arsenic metabolism. Many people in arsenic exposed regions of Bangladesh and India practice fasting for at least one month every year when they refrain from consumption of food and fluid during daylight hours. How such practices may modulate arsenic metabolism has not been previously investigated. This study investigated this issue by determining total arsenic and its species in urine samples from a group of 29 unexposed volunteers at the beginning of the fasting and at the end of approximately 12 h of fasting period. Inductively coupled plasma mass spectrometry (ICP-MS) and high performance liquid chromatography (HPLC) coupled with ICP-MS was used to measure the total arsenic and arsenic speciation in the urine samples, respectively. The mean total levels of arsenic at the beginning of fasting (18.3 microg g(-1) creatinine) and at the end of approximately 12 h of fasting (17.7 microg g(-1) creatinine) did not differ significantly (p > 0.05). However, the percentages of urinary arsenic as the methylated arsenic species methylarsonate (MA) were found to be significantly different (p < 0.05) and this species was observed more frequently at the end of fasting, although its overall concentration was similar. There were no significant differences (p > 0.05) in both the concentrations and percentages of other urinary arsenic species detected, namely arsenobetaine (AB) and dimethylarsinate (DMA). Arsenite (As(III)) and arsenate (As(V)) were also analyzed, but were not detected. We conclude that fasting for a period of 12 h results in a significant increase in the percentage of urinary arsenic as MA, and its frequency of detection in the volunteers at the end of the fasting period is almost nine fold higher. This suggests that metabolism of arsenic is altered by fasting.