Effects of 2,3-Dimercapto-1-propanesulfonic Acid (DMPS) on Tissue and Urine Mercury Levels following Prolonged Methylmercury Exposure in Rats

Abstract

Methylmercury, a potent neurotoxicant, accumulates in the brain as well as the kidney during chronic exposure. We evaluated the capacity of 2,3-dimercapto-1-propanesulfonic acid (DMPS), a tissue-permeable metal chelator, to reduce brain, kidney, and blood Hg levels and to promote Hg elimination in urine following exposure of F-344 rats to methylmercury hydroxide (MMH) (10 ppm) in drinking water for up to 9 weeks. Inorganic (Hg2+) and organic (CH3Hg+) mercury species in urine and tissues were assayed by cold vapor atomic fluorescence spectroscopy (CVAFS). Following MMH treatment for 9 weeks, Hg2+ and CH3Hg+ concentrations were 0.28 and 4.80 microg/g in the brain and 51.5 and 42.2 microg/g in the kidney, respectively. Twenty-four hours after ip administration of a single DMPS injection (100 mg/kg), kidney Hg2+ and CH3Hg+ declined 38% and 59%, whereas brain mercury levels were slightly increased, attributable entirely to the CH3Hg+ fraction. Concomitantly, Hg2+ and CH3Hg+ in urine increased by 7.2- and 28.3-fold, respectively, compared with prechelation values. A higher dose of DMPS (200 mg/kg) was no more effective than 100 mg/kg in promoting mercury excretion. In contrast, consecutive DMPS injections (100 mg/kg) given at 72-h intervals significantly decreased total mercury concentrations in kidney, brain, and blood. However, the decrease in brain and blood mercury content was restricted entirely to the CH3Hg+ fraction, consistent with the slow dealkylation rate of MMH in these tissues. Mass balance calculations showed that the total amount of mercury excreted in the urine following successive DMPS injections corresponds quantitatively to the total amount of mercury removed from the kidney, brain, and blood of MMH-exposed rats. These findings confirm the efficacy of consecutive DMPS treatments in decreasing mercury concentrations in target tissue and in reducing overall mercury body burden. They demonstrate further that the capacity of DMPS to deplete tissue Hg2+ is highly tissue-specific and reflects the relative capacity of the tissue for methylmercury dealkylation. In light of this observation, the inability of DMPS to reduce Hg2+ levels in brain or blood may explain the inefficacy of DMPS and similar chelating agents in the remediation of neurotoxicity associated with prolonged MMH exposure.

Healing of Amyotrophic Lateral Sclerosis: A Case Report

“…First, it is applied over a long period. Generally, with prolonged DMPS application, several peaks of mercury are observed in the urine in humans previously exposed to mercury [22], which is possibly due to the redistribution of mercury from deep compartments into tissues that are accessible to DMPS [23][24][25][26]. As it is known that mercury accumulates as inorganic mercury in the brain, it is important to cover these deep compartments by an appropriate therapy.…”

“…Teeth 14,15,17,[24][25][26][27]44, 45, and 47 had gold or ceramic denture. Three teeth with root canal fillings (25)(26)(27) showed apical osteitis.…”

The Contribution of Dental Amalgam to Urinary Mercury Excretion in Children

“…Immediately after urine collection, a 10-mL aliquot was removed and acidified with 1 N HCl. Analysis of total mercury was performed using continuous flow, cold vapor spectrofluorometry as previously described (Pingree et al 2001b). Urinary creatinine concentrations were measured in unacidified urine using a standard colorimetric procedure (Sigma #555-A; Sigma-Aldrich, St. Louis, MO, USA).…”

The Association Between Serotonin Transporter Gene Promoter Polymorphism (5-HTTLPR), Self-Reported Symptoms, and Dental Mercury Exposure

“…Analysis of total mercury in urine samples was performed using continuous-flow, cold-vapor spectrofluorometry, as previously described (Pingree et al, 2001). Urine samples were analyzed in triplicate and the geometric mean of the three analyses was computed as the Hg concentration of the sample.…”