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Human metabolism of arsenic is altered by fasting

(17.01.2007)


Background
Millions of people in some of the poorest regions of the world (e.g. Bangladesh, West Bengalen) are exposed to high levels of arsenic through contaminated drinking water (see EVISA news). Long-term exposure to arsenic in drinking water is known to cause cancer of the skin, lungs, bladder and kidneys as well as causing changes to the skin such as pigmentation and thickening. There are indications that the development of cancer caused by arsenic exposure in such populations is besides other factors dependent on dietary and nutritional factors which can modulate arsenic metabolism.

Many of the people affected practice fasting for at least one month every year during Ramadan when they refrain from consumption of food and fluid during daylight hours. How such practices may modulate arsenic metabolism has not been previously investigated.

The new study
Parvez Haris at De Montfort University in Leicester and colleagues investigated this issue by determining total arsenic and arsenic speciation in urine samples from a group of 29 volunteers in the UK.  The subjects, not exposed to contaminated water, provided urine samples 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 µg g–1 creatinine) and at the end of approximately 12 h of fasting (17.7 µg 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.

The researchers concluded 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.


The original study

 Eid I. Brima, Richard O. Jenkins, Paul R. Lythgoe, Andrew G. Gault, Dave A. Polya, Parvez I. Haris, Effect of fasting on the pattern of urinary arsenic excretion, J. Environ. Monit., 9/1 (2007) 98. DOI: 10.1039/b613340a


 Related studies:

 P.L. Goehring, H.V. Aposhian, M.J. Mass, M. Cebrian, B.D. Beck, M.P. Waalkes, The enigma of arsenic carcinogenesis: role of metabolism, Toxicol. Sci., 49 (1999) 5-14. DOI: 10.1093/toxsci/49.1.5

Felecia S Walton, Stephen B Waters, Summer L Jolley, Edward L LeCluyse, David J Thomas, Miroslav Styblo, Selenium compounds modulate the activity of recombinant rat AsIII-methyltransferase and the methylation of arsenite by rat and human hepatocytes, Chem. Res. Toxicol., 16 (2003) 261-265. DOI: 10.1021/tx025649r

C.A. Loffredo, H.V. Aposhian, M.E. Cebrian, H. Yamauchi, E.K. Silbergeld, Variability in human metabolism of arsenic, Environ. Res. (U.S.A), 92 (2003) 85-91. DOI: 10.1016/s0013-9351(02)00081-6

Zuzana Drobná, Stephen B. Waters, Felecia S. Walton, Edward L. LeCluyse, David J. Thomas, Miroslav Styblo, Interindividual variation in the metabolism of arsenic in cultured human hepatocytes, Toxicol. Appl. Pharmacol., 201 (2004) 166-177. DOI: 10.1016/j.taap.2004.05.004

Vivian W.M. Lai, Yongmei Sun, Eon Ting, William R. Cullen, Kenneth J. Reimer, Arsenic speciation in human urine: are we all the same ?, Toxicol. Appl. Pharmacol., 198/3 (2004) 297-306.   DOI: 10.1016/J.TAAP.2003.10.033

K.T. Suzuki, Metabolomics of arsenic based on speciation studies, Anal. Chim. Acta, 540/1 (2005) 71-76. DOI: 10.1016/j.aca.2004.09.092

Blakely M. Adair, Stephen B. Waters, Vicenta Devesa, Zuzana Drobna, Miroslav Styblo, David J. Thomas, Commonalities in Metabolism of Arsenicals, Environ. Chem., 2/3 (2005) 161-166. DOI: 10.1071/EN05054

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Maria Mercedes Meza, Lizhi Yu, Yelitza Y. Rodriguez, Mischa Guild, David Thompson, A. Jay Gandolfi, Walter T. Klimecki, Developmentally Restricted Genetic Determinants of Human Arsenic Metabolism: Association between Urinary Methylated Arsenic and CYT19 Polymorphisms in Children, Environ. Health Perspect., 113/6 (2005) 775-781. DOI: 10.1289/ehp.7780

Zi-juan Liu, Miroslav Styblo, Barry P. Rosen, Methylarsonous Acid Transport by Aquaglyceroporins, Environ. Health Perspect., 114/4 (2006) 527-531. DOI: 10.1289/ehp.8600

Samuel M. Cohen, Lora L. Arnold, Michal Eldan, Ari S. Lewis, Barbara D. Beck, Methylated Arsenicals: The Implications of Metabolism and Carcinogenicity Studies in Rodents to Human Risk Assessment, Crit. Rev. Toxicol., 36/2 (2006) 99. DOI: 10.1080/10408440500534230

 W. Jay Christian, C. Hopenhayn, J.A. Cemteno, T. Todorov, Distribution of urinary selenium and arsenic among pregnant women exposed to arsenic in drinking water, Environ. Res. (U.S.A), 100/1 (2006) 115-122. DOI: 10.1016/j.envres.2005.03.009


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