Mercury Absorption, Accumulation and Excretion


In the page "Where Does the Mercury Go?" I rightly complain that there is not a system model describing mercury poisoning from dental amalgam.

Thanks to the work of Jesper Bo Nielsen, there is an incredible start using the mouse experimental model. When taken together, the following report summaries show that there is plenty enough knowledge to start constructing that system model.

"Candida's Fire" ties all of these facts together with the yeast pathogen at the center converting inorganic mercury to methylmercury, and selectively poisoning the human immune system nuetrophils.

"Toxicokinetics of Mercuric Chloride and Methylmercuric Chloride in Mice"; Journal of Toxicology and Environmental Health; 37:85-122; 1992; Jesper Bo Nielsen; Department of Environmental Medicine, Odense University, Denmark.

"The toxicokinetics of inorganic mercury in mice depend on dose size, administration route, and sex, whereas the mouse strain used is less important. The "true absorption" of a single oral dose of HgCl2 was calculated to be about 20% at two different dose levels. Earlier studies that did not take into account possible excretion of absorbed mercury and intestinal reabsorption during the experimental period report 7-10% intestinal uptake. The higher excretion rates observed after oral than after than after peritoneal administration of HgCl2 are most likely due to differences in disposition of systematically delivered and retained mercury."

"After methylmercury administration, mercury excretion followed first-order kinetics for 2 weeks, independently of administration route, strain, or sex. However, during longer experimental periods, the increasing relative carcass retention (slower rate of excretion) caused the elimination to deviate from first order kinetics. Extensive differences to the toxicokinetics of methylmercury with respect to excretion rates, organ deposition, and blood levels were observed between males and females."

Both Mercury Experiments
1. 203Hg radioisotope was used to trace mercury within the mice.
2. 4 strains of mice, 3 inbred, 1 out bred.
3. 203Hg tracking was calibrated with isoplots.

Orally Ingested Mercuric Chloride
1. 20% absorbed.
2. Male mice retained 2:1 over females at 14 days.
3. Whole body retention at 14 days inversely related to dose.
4. Strain dependent rates of excretion.
5. Retention mainly in kidneys, liver, and carcass at 14 days.
6. Avg. brain accumulation approx. 1% of total retained at 14 days.
7. Strain dependent variations in preferential retention locations.

Orally Ingested MethylMercuric Chloride
1. 100% absorbed.
2. Female mice retained 2:1 over males at 14 days.
3. Whole body retention at 14 days inversely related to dose.
4. Strain dependent rates of excretion.
5. Retention 65-75% in carcass, 8-10% liver, 5-20% kidneys
6.Brain 1-1.6% accumulation at 14 days.
7. Significant strain dependent variations in preferential retention locations.
8. Hair is a major deposit for mercury after exposure to methylmercury.

"Massive Oral Ingestion of Elemental Mercury"; Clinical Toxicology, 31(3), 487-492; 1993;Ja-Liang Lin, MD; Paik-Seong Lim, MD; Chang Gung Memorial Hospital, Kuang Tien Genera Hospital, Taiwan, Republic of China.

Case Study
1. Individual with 30 years experience repairing mercury based sphymomanometers, hand tremor evident.
2. Intentionally ingested 220ml, approximately 3 kg of metallic mercury.
3. Clearance of measured bulk with feces took 2 weeks.
4. Patient demonstrated 100+ ppb urine mercury levels.
5. Readmitted 6 months later for glycemic control, mild jaundice and impaired liver function.
6. 12 months after incident 6 ppb urine mercury level, and restored liver function.
7. Delayed liver dysfunction 6 months after apparent bowel clearance problematic to treating physicians.

"Toxicity, Bioavailability and Metal Speciation"; Comp. Biochem. Physiol. Vol 106C, No. 3, pp 585-595, 1993; SB Jonnalagadda, PVV Prasada Rao; Department of Chemistry; and Department of anatomy, University of Zimbabwe

"5. Aquatic organisms absorb and retain Hg in the tissues, as methylmercury, although most of the environmental Hg to which they are exposed is inorganic. The methylmercury in fish arises from the bacterial methylization of inorganic Hg. Methylmercury in the human diet is almost completely absorbed into the bloodstream. The nervous system is the principal target tissue affected by methylmercury in adult human beings, while kidney is the critical organ following the ingestion of Hg(II) salts."

Review of Mercury Facts
1. There is no evidence in the literature for the synthesis of organomercury compounds in human and mammalian tissues (WHO, 1976.)
2. The conversion of methylmercury to inorganic mercury is considered a key step in the process of excretion of mercury after exposure to methylmercury (WHO, 1990).
3. Elemental mercury vapor readily crosses the blood brain barrier.
4. Oxidation of elemental mercury into divalent mercury ions trap it within the brain.
5. 80% of inhaled metallic mercury vapor is retained by the body, liquid mercury is poorly absorbed by the GI.
6. Reduction of divalent mercury to metallic mercury has been demonstrated in animals and humans.
7. Inorganic mercury compounds are probably absorbed from the human GI tract to a level of less than 10%.
8. Kidney is the main depository of mercury after the administration of elemental mercury vapor or inorganic mercury compounds; 50-90% of body burden in animals.
9. In humans methylmercury in the diet is almost completely absorbed into the blood stream and is distributed to all tissues in about 4 days.
10. Methylmercury is converted to inorganic mercury, assumed to be Hg2+ in mammals.
11. The nervous system is the principal target tissue for the effects of methylmercury on adult human beings.
12. Renal/kidney damage is one of the most frequently described non-nueral effects of mehylmercury.

"Treatment of acute methylmercury ingestion by hemiodialysis with N-acetylcysteine (NAC) infusion and 2,3-dimercaptopropane sulfonate (DMPS)"; Lund ME; Banner W Jr; Clarkson TW; Berlin M; J Toxicol Clin Toxicol, 22:1, 1984 July, 31-49.

Case Study and Fact Review
1. Amount of methylmercury ingested estimated at 45 mg.
2. Urinary organic mercury elimination rate increased 40 fold during dialysis with NAC infusion.
2. Urinary organic mercury elimination rate increased 84 fold following dialysis with NAC infusion.
3. DMPS was used concurrently with Zinc and Copper containing vitamins, and did not perform as expected.
4. 75% of urinary mercury excretion in this case was organic mercury.
5. Methylmercury undergoes extensive reabsorption back into the human when excreted via bile into the small intestine.
6. Data from this one case indicates NAC more effective than D-penicillamine.

"Mechanisms of Hepatic Methylmercury Uptake; Journal of Toxicology and Environmental Health, 46:343-353, 1995; Nazzareno Ballatori, Anh T. Truong; Department of Environmental Medicine, University of Rochester School of Medicine.

Facts and Findings
1. Methylmercury is transported into bile as the methylmercury-glutathione complex (CH3Hg-SG)
2. Initial rates of hepatic methylmercury uptake are enhanced by cysteine or glutathione (GSH).
3. In contrast to methylmercury, inorganic mercury uptake are slightly diminished by cysteine or GSH administration.
4. Liver uptake of methylmercury was higher when presented as cysteine or GSH compound.
5. There is no difference in liver methylmercury uptake between D-cysteine and L-cysteine.
6. Kidney uptake is stimulated 5-10 fold when administered as a mercaptide with either D-cysteine, L-cysteine, NAC, GSH, L-penacillamine, or D-penacillamine.
7. Kidney uptake is the same between D-cysteine and L-cysteine.
8. In blood most of methylmercury is found within the red blood cells, bound to hemoglobin.
9. Methylmercury in plasma is bound largely to plasma proteins and thiol compounds: L-cysteine and GSH.
10. Most of the Methylmercury in plasma is bound to proteins.
11. Methylmercury becomes highly concentrated on liver cell membranes.
12. Bile excretion rate low compared to liver extraction rate.

"Up-regulation of Glutathione Synthesis in Rat Kidney by Methylmercury"; Biochemical Pharmacology, Vol. 50, No 10, pp. 1719-1724, 1995; JS Woods, ME Ellis; Department of Environmental Health, School of Public Health and Community Medicine, University of Washington, Seattle, WA 98195, USA

Facts and Results
1. y-glutamylcysteine synthetase (GCS) is the first and rate limiting enzyme in the synthesis of glutathione (GSH).
2. Depletion of cellular GSH, either by thiol conjugation or by inhibition of GCS has been postulated to underlie oxidative tissue damage caused by metals and other chemical agents.
3. Prolonged exposure to methylmercury increases kidney GSH levels.
4. GSH protects the kidney during methlymercury stress.
5. Kidney rapidly converts methylmercury to Hg2+

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Copyright ©1996 / 1997 Jeff Clark