Treatment of acute methylmercury ingestion with NAC

Title: Treatment of acute methylmercury ingestion by hemodialysis withN-acetylcysteine (Mucomyst) infusion and 2,3-dimercaptopropane sulfonate.Title Abreviation: J Toxicol Clin Toxicol Date of Pub: 1984 Jul Author:Lund ME; Banner W Jr; Clarkson TW; Berlin M; Issue/Part/Supplement: 1Volume Issue: 22 Pagination: 31-49 MESH Headings: Acetylcysteine (*TU);Administration, Oral; Adult; Benztropine (PO); Case Report; Haloperidol(PO); Hemodialysis (*); Human; Kinetics; Male; Mercury (UR); MethylmercuryCompounds (BL/ME/*PO); Penicillamine (TU); Suicide, Attempted; Support,U.S. Gov't, P.H.S.; Unithiol (TU); -RN-; Journal Title Code: KANPublication Type: JOURNAL ARTICLE Date of Entry: 841126NEntry Month: 8502Country: UNITED STATES Index Priority: 1 Language: Eng Unique Identifier:85033828 Unique Identifier: 85033828 ISSN: 0731-3810

Abstract: A case of acute methylmercury ingestion was treated sequentially with oral D-penicillamine, hemodialysis during N-acetylcysteine (NAC) infusion, and 2,3-dimercaptopropane sulfonate (DMPS) an experimental oral agent. Urinary organic mercury elimination rate increased almost 40-fold during and84-fold after hemodialysis with NAC infusion, compared with elimination during initial D-penicillamine therapy. Mean clearance during hemodialysis was only 13 ml/min with an extraction rate of 3.7 mcg/min. Although wholeblood mercury concentrations decreased from 568 to 265 ng/ml during dialysis, a rebound to 525 ng/ml occurred. A total of 1.6 mg mercury was renally eliminated during hemodialysis and in the following 24 hours. A total of 3.3 mg of predominantly organic mercury was renally eliminated during 18 days of combined therapies. Since renal elimination of inorganicmercury is seen with chronic methylmercury poisoning, the high ratio of organic to inorganic mercury in urine supports the acute nature of this exposure. DMPS was begun on day 4 and during the two weeks of administration whole blood concentrations fell by 15% to 355 ng/ml. An expected decrease inelimination half-life to 10 days was not observed during DMPS therapy, possibly due to concurrent administration of vitamins containing zinc andcopper. The amount of methylmercury ingested was estimated as 45 mg, based on a post-distribution blood concentration of approximately 450 ng/ml. The patient developed no symptoms of methylmercury poisoning during the one year after the episode. We conclude that NAC may be useful to enhance renal elimination of methylmercury and merits further investigation as a potential binding agent to reduce the body burden of methylmercury.

Title: Cytotoxicity of heavy metals in the human small intestinalepithelial cell line I-407: the role of glutathione. Title Abreviation: JToxicol Environ Health Date of Pub: 1994 Nov Author: Keogh JP; Steffen B;Siegers CP; Issue/Part/Supplement: 3 Volume Issue: 43 Pagination: 351-9MESH Headings: Cadmium (TO); Cell Line; Chlorides (TO); Copper (TO);Epithelium (CY/DE); Glutathione (*PH); Human; Intestine, Small (CY/*DE);Lead (TO); Mercuric Chloride (TO); Metals (*TO); Neutral Red; Nitrates(TO); Thallium (TO); -RN-; Journal Title Code: KAA Publication Type:JOURNAL ARTICLE Date of Entry: 941129NEntry Month: 9502 Country: UNITEDSTATES Index Priority: 2 Language: Eng Unique Identifier: 95055873 UniqueIdentifier: 95055873 ISSN: 0098-4108

Abstract: Cytotoxicities of metal salts were determined in the intestinal epithelial cell line I-407 in microwell culture plates over 48 h using the widely utilized and accepted neutral red uptake procedure. Rank order cytotoxicities induced by themetal salts (in terms of LC50 values) were found to be HgCl2 (32 microM) >CdCl2 (53 microM) > CuCl2 (156 microM) > T12SO4 (377 microM) > Pb(NO3)2(1.99 mM). Combined administration of the two most toxic metals at their LC50's showed that their toxicities were not additive or synergistic. The role of glutathione in determining toxicity induced by the metal salts inthese cells was assessed by inhibition of its synthesis. Buthioninesulfoximine pretreatment at 1 mM, which was not toxic to the cells, caused sustained reduction in cellular glutathione content (to 13.8% after 48 h) and increased toxicities induced by HgCl2 (5.7-fold) and CuCl2 (1.44-fold) as shown by reductions in the LC50 values. Toxicity induced by the other metals remained unaffected. Administration of glutathione with either HgCl2 or CdCl2 did not protect the cells against their toxicity, and in the caseof cadmium its toxicity was exacerbated. N-Acetylcysteine diminished toxicity induced by mercury but not cadmium. N-acetylcysteine enhances in vitro the intracellular killing of Staphylococcus aureus by human alveolar macrophages and blood polymorphonuclear leukocytes and partially protects phagocytes from self-killing.

Also make sure to read these books: Poison in Your Teeth: Mercury Amalgam (Silver) Fillings...Hazardous to Your Health! and Mercury Detoxification by Tom McGuire